Translating Basic Science to Improve the Mental Health of Children and Young People by IOPPNPress

The Child and Adolescent Mental Health Services Clinical Academic Group 2018 Projects Day

Translating Basic Science to Improve the Mental Health of Children and Young People

The Child and Adolescent Mental Health Services Clinical Academic Group 2018 Projects Day

Translating Basic Science to Improve the Mental Health of Children and Young People

Foreword This book collects together summaries of the current research taking place in the Child & Adolescent Mental Health Clinical Academic Group (CAMHS CAG) at the time of our conference, June 29th 2018. These summaries demonstrate the breadth of our research and demonstrate how its spans the translational pipeline from basic science through new diagnostic tools and interventions culminating in implementation not only in our own clinical services and local community but also nationally and internationally. All the projects summarised in this book have the same ambitions: to prevent and treat more effectively mental health problems and disorders in youth. The majority of mental disorders begin in childhood and adolescence; by reducing youth mental disorders, we will ultimately improve mental health for people of all ages. These diverse summaries demonstrate a number of the qualities that characterise successful and high-impact research. First, they involve collaborations amongst scientists with different disciplines and between scientists and clinicians. These collaborations benefit from the rich diversity of academics at the Institute of Psychiatry, Psychology and Neuroscience, but also more widely across the King’s campus as well as nationally and internationally. Second, our research makes use of cutting-edge methods that allow us to address scientific issues in new, and potentially more effective, ways. Third, our research questions are developed and prioritised through close working relationships with clinicians and are driven by the unresolved clinical issues that are experienced by our patients. These include making accurate and timely diagnoses, providing interventions that are effective, cost-effective with a minimum of adverse effects. We are also driven by the ambition to prevent the occurrence of mental health problems in the first instance and thus to build programmes that foster resilience and detect risk early on, before the emergence of symptoms. This book provides just a snap shot in time of our current research. Yet, we are not standing still. Our ambition is to harness the great opportunities provided by new scientific methods to gain novel insights into the causes of and treatments for youth mental disorders. We plan to build a state of the art hub for children and young people’s mental health, sited at the heart of the Maudsley campus. This will bring together researchers and clinicians and provide the clinical research facility that is essential to achieve our ambitions. Co-located with our clinical services, the close working relationships between clinicians and researchers will be further strengthened and provide greater research opportunities for our patients.

Emily Simonoff Professor of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience, King’s College London Academic Lead of CAMHS CAG, King’s Health Partners

Acknowledgements Many people have contributed to the production of this book and in the organisation of Projects Day. Ashleagh Joseph-Quinn and Janet Fullerton provided administrative support for all aspects of organisation. Julie Burnell ensured that the finances to support this event were in place. Olga Andreevskikh organised the webpage to showcase this event. We thank the Communications and Events team, including Louise Pratt, Hannah Warren, Krystal Rose and Alexandra Booth. Eve Blanchard provided essential liaison with our colleagues in the South London and Maudsley NHS Foundation Trust. The greatest thanks go to the CAMHS CAG Projects Day team, Marion Criaud, Steve Lukito and Emerald Sheldon. Their tireless support and hard work over a number of months was essential to every aspect of the 2018 Projects Day: the event and its smooth running and the collation of our research.

Table of Contents Foreword

Acknowledgements

Childrenâ&#x20AC;&#x2122;s Development and Neuroplasticity

Brain imaging in babies (BIBS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Examining structural connectivity in 24-month-old toddlers using diffusion weighted magnetic resonance imaging: A feasibility study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 The development of episodic prospection and its link to future oriented decisions in adolescence: Behavioural and electrophysiological correlates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Neural, physiological and behavioural correlates of transitioning from recreation to work in young children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Neuroimaging and the brain plasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 The neurophysiological correlates of physical childhood abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Effects of meditation on brain structure and function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Effects of singing training on brain structure, function and cognition . . . . . . . . . . . . . . . . . . . . . . . 13

Neurodevelopmental Disorders

British study of infant siblings (BASIS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Improving outcomes for people with autism spectrum disorders by reducing mental health problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Developing an observational coding scheme for parent-child interaction in autism spectrum disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Understanding the relationship between parental expressed emotion and the development/ maintenance of additional psychopathology in young people with ASD . . . . . . . . . . . . . . . . . . . . 22 Exploring the neurocognitive and electrophysiological correlates of emotional and behavioural problems in young people with autism spectrum disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Development of the observation schedule for children with autism spectrum disorders (ASD)â&#x20AC;&#x201C; anxiety and behaviour (OSCA-AB): A new measure of parent and child behaviour for use with children with ASD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Why do people with autism spectrum disorders fare so differently in adult life? . . . . . . . . . . . . . . 28 The cognitive and MRI correlates of attention-deficit/hyperactivity disorder symptoms in young adults with autism spectrum disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Specificity of executive function and theory of mind performance in relation to attention-deficit/ hyperactivity symptoms in autism spectrum disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Detection of suicidality in adolescents with autism spectrum disorder: Developing a natural language processing approach for use in electronic health records . . . . . . . . . . . . . . . . . . . . . . . . . 36 Predictors of death by suicide in autism spectrum disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Biomarkers of childhood-onset neurodevelopmental disorders (BioNeD) . . . . . . . . . . . . . . . . . . . 40 Development of the tailored Rett intervention and assessment longitudinal (TRIAL) database and the Rett evaluation of symptoms and treatments (REST) questionnaire . . . . . . . . . . . . . . . . . . . . 42 iii

Sarizotan treatment of apneas in Rett syndrome (STARS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Systematic phenotyping in neuroimaging (SPIN) study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Early development in tuberous sclerosis (EDiTS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Tuberous sclerosis 2000 study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Developmental neuroimaging in ADHD and related disorders: From biomarker search to neurotherapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Specificity of brain deficits: Comparing brain abnormalities between ADHD, ASD and OCD . . 50 Functional maturation abnormalities in autism spectrum disorder relative to healthy controls and ADHD patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 An fMRI study on the effects of the serotonin-agonist Fluoxetine on brain activation in adolescents with ADHD and with autism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 A pilot PET study to test the effects of opioid release after a single dose of amphetamines . . . . . . 57 Effects of a single dose of Guanfacine and Lisdexamfetamines on brain activation in ADHD children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Diagnosing ADHD patients based on brain structure and function patterns . . . . . . . . . . . . . . . . . 60 A proof of concept study of fMRI neurofeedback in ADHD adolescents . . . . . . . . . . . . . . . . . . . . 62 A large placebo-controlled randomised controlled trial of the efficacy of fMRI neurofeedback in ADHD children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 A novel neurotherapy of transcranial direct current stimulation combined with cognitive training in ADHD children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Digital health monitoring systems for ADHD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Emotional and Behavioural Disorders

The origins of cognitive deficits in victimised children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Child maltreatment and obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Child maltreatment and inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Psychological consequences of child trafficking: A historical cohort study of trafficked children in contact with secondary mental health services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 A pilot randomised controlled trial of cognitive behavioural therapy for adolescents with body dysmorphic disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Ritualised eating in young people with obsessive compulsive disorder: Clinical characteristics and treatment outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Obsessive-compulsive disorder multi-cultural youth project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 How resistant is “treatment resistant” obsessive compulsive disorder in youth? . . . . . . . . . . . . . . . 82 A pilot study of internet-delivered cognitive behavioural therapy for adolescents with obsessivecompulsive disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Long-term outcomes of cognitive behavioural therapy for adolescent body dysmorphic disorder 85 Longitudinal assessment of manic symptoms (LAMS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Suicidality: Treatment occurring in paediatrics (STOP) – Development of a comprehensive webbased methodology for the assessment and monitoring of suicidality and its mediators in children and adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 Feasibility randomised controlled trial of the “DISCOVER” workshop programme for 15-18 year olds with anxiety and/or depression in clinic settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Mindfulness-based cognitive therapy for depression in adolescents . . . . . . . . . . . . . . . . . . . . . . . . 90

Trauma-focused cognitive behaviour therapy post-traumatic stress disorder (PTSD) in young children aged 3 to 8 years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Cognitive therapy for the treatment of post-traumatic stress disorder (PTSD) in youth exposed to multiple traumatic stressors: A phase II randomised controlled trial . . . . . . . . . . . . . . . . . . . . . . . . 94 Randomised control trial of a CBT trauma recovery program in Palestinian schools . . . . . . . . . . . 95 Internet-delivered cognitive therapy (iCT) for young people with post-traumatic stress disorder (PTSD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Multi-centre aggression subtyping research in conduct syndromes (MATRICS) . . . . . . . . . . . . . 97 Anger rumination in adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Assessing effective participation in vulnerable juvenile defendants . . . . . . . . . . . . . . . . . . . . . . . . . 99 Assessing knowledge of court proceedings in 10 and 14-year old children . . . . . . . . . . . . . . . . . . . 100 Language and social skills in teenage girls at-risk and not at-risk of future offending . . . . . . . . . . 101 Prevalence and patterns of diagnostic transitions in child and adolescent mental health services . 102 MILESTONE study: Development and validation of a suite of measures to manage and strengthen transition from child to adult mental health care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Eating Disorders and Associated Conditions

105

Fear of food - Attention bias for food cues in adults and adolescents with anorexia nervosa . . . . . 106 Social information processing in adolescents with eating disorders . . . . . . . . . . . . . . . . . . . . . . . . . 107 Development of the child and adolescent over and under controlled traits measure (OUT-M) . . . 108 Impact of autism spectrum disorder traits on treatment outcomes of eating disorders in girls . . . . 110 When the world seems pro-ana: Adolescentsâ&#x20AC;&#x2122; experience of social media and eating disorders . . 112 Intensive treatment programme (ITP): A service evaluation of the effectiveness of day patient treatment for adolescents with a restrictive eating disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Outreach to adolescents with symptoms of bulimia nervosa: Increasing accessibility of treatment 116 Developing treatments for bulimia nervosa in adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Cognitive behavioural therapy for obsessive compulsive disorder with adolescents recovering from anorexia: A case series . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Attachment and mentalisation as predictors of outcome in family therapy for adolescent anorexia nervosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Pathways in mental health care following treatment of eating disorders in childhood and adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Inpatient Care and Psychosis

125

The assessment and management of children in need of inpatient input presenting with psychotic symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 What was helpful questionnaire (WHQ): Psychometric properties of a novel tool designed to capture parental perceived helpfulness of interventions in children requiring mental health inpatient care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Clinical correlates of comorbid chronic tics and Tourette syndrome in a national inpatient childrenâ&#x20AC;&#x2122;s unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Emergency mental health admissions for children: A naturalistic study . . . . . . . . . . . . . . . . . . . . . 130

Measuring stigma in children receiving mental health treatment: Validation of the paediatric selfstigmatization scale (PaedS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Hospital admission for severe paediatric dissociative disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Determination of psychosis-related clinical profiles in children with autism spectrum disorders using latent class analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Predictors of multiple treatment failure of antipsychotics in early onset psychosis . . . . . . . . . . . . . 136 Disparities in detention: An investigation into relationships between sociodemographic status and compulsory psychiatric care among children and adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 The role of ethnicity and diagnosis in rates of adolescent psychiatric admission and compulsory detention: A longitudinal case-note study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Coping with unusual experiences for 12 to 18 year olds (CUES+). A transdiagnostic randomised controlled trial of the effectiveness of cognitive behaviour therapy in reducing distress associated with unusual experiences in adolescent mental health services . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Comparison of effectiveness and cost-effectiveness of an intensive community supported discharge service versus treatment as usual for adolescents with psychiatric emergencies: a randomised controlled trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

Parenting and Caregiving

147

Can a parent-focused intervention reduce emotional and behavioural problems in young children with ASD? The autism spectrum treatment and resilience (ASTAR) feasibility and pilot trial . . . 148 Predictive parenting: Developing a new group parent intervention for behavioural and emotional problems in children with ASD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Managing anxiety in children and young people with autism spectrum disorder . . . . . . . . . . . . . . 151 Early caregiving predicts attachment representations in adolescence: Findings from two longitudinal studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Personalised assessment and intervention packages for children with conduct problems . . . . . . . . 154 Harnessing the power of individual participant data in a meta-analysis of the benefits and harms of the incredible years parenting program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 Multi-systemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): A randomised controlled trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Randomised controlled trial of functional family therapy (FFT) for offending and antisocial behaviour in UK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Helping families programme: An innovative parenting intervention for families with complex and multiple morbidities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Empowering parents, empowering communities (EPEC): A popular, cost effective parenting programme for socially disadvantaged and excluded families . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

Community and School-based Intervention

165

Paediatric autism communication trial-generalised (PACT-G) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 Social contagion?: Using administrative data to examine risk factors in schools for indicators of adolescent adversity and distress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Linking education, social care and electronic health records for children attending mental health services. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 Evaluation of a body satisfaction programme â&#x20AC;&#x153;Happy Being Meâ&#x20AC;?: Delivery in schools by clinicians and teachers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

CUES-Ed: Service evaluation of a cognitive behavioural early mental health intervention for whole classes of primary school children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 School-based early intervention for anxiety and depression in older adolescents: A feasibility randomised controlled trial of a self-referral stress management workshop programme DISCOVER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 The acceptability and feasibility of implementing a brief dialectical behaviour therapy (DBT) skills group in pupil referral units (PRU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 DISCOVER programme: Studentsâ&#x20AC;&#x2122; views of a school-based CBT workshop and experiences of waiting for a service . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 Computerised CBT for depressed adolescents: Randomised controlled trial . . . . . . . . . . . . . . . . . 180

vii

CAMHS CAG Projects Day 2018

Childrenâ&#x20AC;&#x2122;s Development and Neuroplasticity

CAMHS CAG Projects Day 2018

Brain imaging in babies (BIBS)

Investigators: Dr Grainne McAlonan1; Dr Vaheshta Sethna1; Dr Andreina Mendez1; Emily Perry1; Li Faye Lim1; Dr Ines Pote1; Rali Dimitrova1; Laura Ajram1; Dr Alice Durieux1; Ayesha Javed1; Dr Nantia Iakovidou2; Dr Federico Fiori2,3; Prof Paramala Santosh2,3 1 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s C ollege London (KCL); 2 Department of Child & Adolescent Psychiatry, IoPPN, KCL; 3 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust

Lay Summary: The Brain Imaging in Babies study (BIBS) aims to improve understanding of how a baby's brain develops from before birth up until 3-4 years of age. Working with children from a variety of backgrounds and communities, this study aims to use a combination of state of the art diagnostic tools such as MRI scans alongside traditional behavioural assessments and analytics to capture the earliest information on infant brain development. State of Progress: Ongoing Abstract: Background: The BIBs study is part of the wider EU-AIMS project (European Autism Interventions - A multicentre Study for developing new medications) whose focus is to identify biomarkers for Autism Spectrum Disorder (ASD) and other related conditions such as Attention Deficit Hyperactivity Disorder (ADHD). Methods: The study uses the state-of-the-art neuro-imaging techniques such as MRI and behavioural assessments to provide the earliest information on infant brain development. MRI scans allow pictures of the babyâ&#x20AC;&#x2122;s brain to be taken without using harmful radiation. Cluster analysis will be used for the development of clustering algorithms to identify risk. Results: As well as learning more about typical child neurodevelopment, this project will help in the identification of factors that help predict whether a child is at risk of developing traits in conditions allied to neurodevelopment disorders such as ASD, ADHD etc. In the longer term, this will help in the targeting of useful interventions at early stages to children most at risk. Conclusion: It is hoped that this project will not only uncover why some people are more vulnerable to conditions like ASD and ADHD, but will also identify potential biological mechanism that might help to confer protection. In the longer term, this will help in the development of better treatments to improve outcomes for all children. Funding: Innovative Medicines Initiative (IMI) and BRC funding for exploring sensor-based technology and the development of clinical decision-making analytics. Publications: Pending 2

Children’s Development and Neuroplasticity

Examining structural connectivity in 24-month-old toddlers using diffusion weighted magnetic resonance imaging: A feasibility study

Investigators: Prof Edmund Sonuga-Barke1, Prof Mitul Mehta2, Dr Sam Wass3, Dr Kasia KostyrkaAllchorne1, Zeynep Suata1, Dr Jonathan O'Muircheartaigh4, Dr Chiara Nosarti5, Prof Serena Counsell6, Prof David Edwards6. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL; 3 School of Psychology, University of East London; 4 Department of Forensic & Neurodevelopmental Sciences, IoPPN, KCL; 5 Department of Psychosis Studies, IoPPN, KCL; 6 Department of Perinatal Imaging & Health, KCL.

Lay Summary: The term structural connectivity refers to an anatomic link between distinct brain regions that is provided by the white matter tracts. Information about structural connectivity allows us to develop a better understanding of the cognitive and behavioural changes associated with typical development. Importantly, disruptions to anatomical connectivity observed in childhood and early adulthood appear to be a common factor associated with a range of mental health disorders (Alnæs et al., 2018). Thus, investigating white matter tracts properties in infancy may be particularly helpful in establishing early neural markers of risk for later psychopathology. In turn, this could allow developing new ways of altering neurodevelopmental pathways leading to conditions, such as, attention deficit hyperactivity disorder, prior to the onset of behavioural symptoms (Sonuga-Barke, 2014). While measuring structural connectivity early in development provides a promising area of research into the neuro-developmental origins of psychological disorders, acquiring magnetic resonance imaging (MRI) data in infants and toddlers is very challenging. On the one hand, MRI is highly sensitive to movement artefacts. On the other hand, young children find it extremely difficult to remain still during image acquisition. Considering the importance of developing new lines of research into the neurodevelopmental origins of common childhood conditions (e.g., ADHD), this study aims to test the feasibility of acquiring MRI data from toddlers. Specifically, the aims are to examine the feasibility of image acquisition during natural sleep and the measurement of structural connectivity in the developing brain. State of Progress: Future Abstract: Identifying early neural markers of psychopathology is particularly important for developing new ways of identifying common childhood psychiatric conditions prior to the onset of behavioural symptoms. Using diffusion-weighted magnetic resonance imaging (MRI), a recent study demonstrated the associations between brain structural connectivity and a range of psychiatric symptoms in genetically vulnerable older children and adolescents (Alnæs et al., 2018). However, the enthusiasm for using neuroimaging methods for establishing such objective neural markers of psychopathology in early childhood may be tempered by the difficulty of conducting imaging research with infants and toddlers. Thus, this study will focus on examining the feasibility of acquiring imaging data from a group of typically developing 24-month-old toddlers. Specifically, it will test the feasibility of participant recruitment, image acquisition during natural sleep and the measurement of structural connectivity in the developing brain. Background: Intrinsic functional organisation of the brain’s neural networks that underpin cognition and complex behaviour is dependent on its structural connectivity. Coordinated activation of the functional networks is enabled through the myelinated white matter tracts that provide an anatomic link between 3

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different areas of grey matter (Ameis & Catani, 2015). Examining white matter tracts’ maturation and their relationship to cognitive performance from the earliest periods of life across the lifespan allows us to develop a better understanding of the cognitive and behavioural changes that occur during typical development (Lebel & Beaulieu, 2011; Peters et al., 2014). In addition to providing insight about healthy development, measuring white matter properties allows investigation of potential consequences of disruptions to early development. For example, research with paediatric clinical populations has shown that white matter abnormalities observed in prematurely born infants were associated with lower cognitive, language and motor performance in toddlerhood (Ball et al., 2017; Barnett et al., 2018). Importantly, investigation of the development of white matter properties during infancy may be a particularly promising area of research conducted to establish early neural markers of risk for later psychopathology. This could allow targeted early interventions to reduce the likelihood of disorder and impairment. In an important recent diffusion-weighted magnetic resonance imaging (MRI) study, Alnaes et al. (2018) demonstrated an association between the properties of two major white matter tracts and a wide spectrum of different psychiatric symptoms in genetically vulnerable adolescents and young adults. This suggests the potential for alterations in structural connectivity as an early transdiagnostic phenotype for a range of psychopathology (Alnæs et al., 2018). Identifying such objective markers of disorder may be particularly important for developing new ways of targeting neuro-developmental pathways to alter trajectories to conditions such as attention deficit hyperactivity disorder (ADHD) prior to the onset of behavioural symptoms (Sonuga-Barke, 2014). Despite the extensive use of neuroimaging research to study structural (e.g., Ashtari et al., 2005; Cao et al., 2010; Silk, Vance, Rinehart, Bradshaw, & Cunnington, 2009) and functional (e.g., Fair et al., 2013; Tomasi & Volkow, 2012; Yu-Feng et al., 2007) brain abnormalities associated with ADHD in older children and adolescents, remarkably little is known about the very early neural underpinnings of this disorder. One explanation for the lack of literature examining the early neural substrates of ADHD may be the overall difficulty in conducting MRI research with very young children. Although many paediatric neuroimaging studies with clinical populations involve routine sedation to minimise participant movement and improve scanning success rates, ethical considerations discourage the use of sedative in research with typically developing healthy children (Dean et al., 2014). However, recently developed procedures for successful image acquisition during natural sleep provide a promising opportunity to improve the efficiency of image acquisition in very young children (Courchesne, 2017; Dean et al., 2014). Nevertheless, many challenges remain in conducting MRI research in very young children. Thus, the aim of this study will be to examine the feasibility of acquiring imaging data from a small group of toddlers. Specifically, we will focus on the three key areas: feasibility of participant recruitment, feasibility of image acquisition during natural sleep and the measurement of structural connectivity. Methods: Participants: Healthy 24-month-old children (±3 months). Image acquisition and analysis: Images will be acquired in the Evelina Newborn Imaging Centre at

the Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London. A high-angular resolution, four shell diffusion-weighted imaging protocol providing maximum time efficiency (Hutter et al., 2018) will be used to acquire images in this study. Analyses will be performed in MRTrix3 using constrained spherical deconvolution (Smith, Tournier, Calamante, & Connelly, 2013). Measures of fractional anisotropy (FA), orientation dispersion index (ODI), neurite density index (NDI) and streamline count will be extracted for all participants. Funding: This work is funded by a grant awarded to Prof Sonuga-Barke from King’s College London to support the start-up of his research. Publication: Pending 4

Childrenâ&#x20AC;&#x2122;s Development and Neuroplasticity

The development of episodic prospection and its link to future oriented decisions in adolescence: Behavioural and electrophysiological correlates

Investigators: Prof Edmund Sonuga-Barke1, Dr Nick Cooper2, Dr Kasia Kostyrka-Allchorne1, Dr Sam Wass3, Prof Mitul Mehta4, Dr Jacqueline Philips-Owen1, Dr Chia-Fen Hsu5 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL), 2 Department of Psychology, University of Essex, 3 School of Psychology, University of East London, 4 Department of Neuroimaging, IoPPN, KCL, 5 Chung Shan Medical University.

Lay Summary: Many aspects of everyday life involve choosing between competing options that differ both in objective value and availability in time. For example, one must resist eating a chocolate (small immediate pleasure) to achieve healthy weight (delayed positive health outcome). Adolescence is a crucial developmental period when individuals must make important choices that may have a long-lasting impact on their adult life (e.g., choose GCSE or A-level subjects, select a future career path). Adult research suggests that inter-temporal decision making is associated with the ability to create mental representations of personally-relevant future events or states, namely, episodic prospection. Specifically, engaging in episodic prospection reduced participantsâ&#x20AC;&#x2122; tendency to devalue future rewards (Benoit, Gilbert, & Burgess, 2011), thus, demonstrating its potential benefits for supporting decision-making and goal-directed behaviour. Moreover, the immediate benefits of engaging in episodic prospection were stronger for individuals who usually were more prone to short-sighted behaviour. This highlights the potential importance of episodic prospection in supporting decision-making in adolescence, a period stereotypically perceived as characterised by risk-taking and short-sightedness. The literature has linked episodic prospection to activity in the default mode network (DMN), an intrinsically connected number of brain regions active during rest and introspective states but attenuated during externally-focused cognitively demanding activity (Raichle et al., 2001). However, to the best of our knowledge, all evidence regarding the neural mechanisms underpinning episodic prospection comes from adult studies. Considering that this self-referential process may play an important role in regulating decision-making behaviour, this study will examine the neural mechanisms underpinning the development of episodic prospection in adolescence. State of Progress: Ongoing Abstract: Research suggests that episodic prospection, described as the ability to mentally envisage personallyrelevant future events and states, has the potential to improve economic decision-making. However, the exact psychological and neural mechanisms that underpin the associations between episodic prospection and decision-making are not clear. Even less is known about these processes in adolescence. Therefore, this study will examine the development of episodic prospection and its associations with future-oriented decisions in 12-18-year-olds. While having EEG recorded, 120 participants will imagine spending money or estimate what money could buy in a potential future scenario. In between envisaging future episodes, they will wait for rewards and rest. We will examine the effects of prospective thinking on economic decision-making measured with a delay discounting task and the neural mechanisms underlying these effects. Background: Much of everyday decision-making involves choosing between competing options that differ both in objective value and temporal availability. Choosing between such options requires evaluating the

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potential benefits of a larger long-term outcome against the cost of a smaller short-term outcome (Wittmann & Paulus, 2009). Although long-term success requires resisting short-term temptations in pursuit of future goals, people tend to decrease the subjective value of a delayed outcome, a process termed delay discounting. Despite the large body of literature describing delay discounting, its psychological and neural underpinnings are not well understood (Wittmann & Paulus, 2009). However, a type of self-referential thought, namely, episodic prospection, appears to be particularly important in this process. Episodic prospection allows one to mentally travel in time to create representations of personally-relevant future events or states (Suddendorf, 2010) and is thought to play an important role in goal-directed, purposeful behaviour. The literature has linked episodic prospection to the activity in the default mode network (DMN), an intrinsically connected number of brain regions including medial prefrontal cortex, posterior cingulate, lateral parietal cortex and temporal gyrus (Fox et al., 2005; Fransson, 2005; Greicius, Krasnow, Reiss, & Menon, 2003; Raichle et al., 2001). The evidence for the relations between DMN activity and episodic prospection comes mainly from neuroimaging research (see Spreng, Mar, & Kim, 2009 for a meta-analysis). However, a recent study used electroencephalography (EEG), coupled with source localisation methods, to map brain activity during prospection onto the putative DMN (Hsu & Sonuga-Barke, 2016). The potential role of episodic prospection in supporting decision-making may be particularly important in adolescence. On the one hand, it is a period that is stereotypically perceived as characterised by risky and short-sighted behaviour. On the other hand, adolescents often must make difficult choices bearing long-term consequences. Therefore, this study will examine the neural mechanisms underpinning the development of episodic prospection and its relation to economic decision-making in adolescence. Specifically, using a region of interest approach, we will examine neural activity localised to DMN regions during episodic prospection. Previous evidence showed that this brain network was also activated during other, qualitatively different states, such as, rest (e.g., Raichle et al., 2001; Raichle & Snyder, 2007) and waiting (Hsu, Broyd, Helps, Benikos, & Sonuga-Barke, 2013). Thus, to distinguish specific DMN activity associated with prospection, we will compare neural correlates across three states: prospection, resting and waiting. Methods: Participants: Participants in this study will be 120 12-17-year-old adolescents and adults. Design: The study will adopt a 4 (age: 12, 14, 16, 18+ years) × 3 (activity: rest, prospection, wait) mixed

factorial design. The dependent variables measured in this study will be: choice index that reflects the frequency of delayed options chosen versus all options chosen, reward index that measures the accumulated reward over trials versus the maximal possible reward (Benoit et al., 2011), participants’ ratings of emotion intensity and vividness of experience, and, EEG power and phase coherence. Tasks: This study will compare brain activity during “rest”, “task” and “waiting”. During the task

participants will either imagine spending money (e.g., £10 in 120 days in a cinema), or estimate what the money could buy in this scenario. After each trial, participants will be asked to rate emotional intensity and vividness of experience, they will also be asked to rate the degree to which they had a feeling of mentally experiencing the activity. During rest, participants will be encouraged to relax and stay focused on the fixation cross displayed on the screen. During wait, participants will choose between waiting 5 minutes to gain a potential reward or progress immediately to the next part of the experiment without a potential reward. Finally, in each trial participants will indicate their hypothetical preference for a larger but delayed reward (e.g., £50 in 180 days) or smaller (e.g., £10) but immediate monetary reward. Funding: This work is funded by a grant awarded to Prof Sonuga-Barke from King’s College London to support the start-up of his research. Publication: Pending 6

Children’s Development and Neuroplasticity

Neural, physiological and behavioural correlates of transitioning from recreation to work in young children

Investigators: Prof Edmund Sonuga-Barke1, Dr Kasia Kostyrka-Allchorne1 & Dr Sam Wass2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 School of Psychology, University of East London.

Lay Summary: Research investigating the development of children’s attention and cognition has focused on measuring optimal performance during laboratory tasks. However, real life does not consist of a series of continuous tasks. Rather, to function effectively, children need to be able to switch between periods of rest or recreational activity to periods of work (i.e. tasks). Adult research suggests that efficient switching between such states involves the ability to modulate a specific brain network - the Default Mode Network (DMN; Raichle et al., 2001) to allow other brain networks required for tasks to work. Almost nothing is known about the development of state switching in children, as all evidence regarding this process comes from adult studies using magnetic resonance imaging (MRI; e.g., Sidlauskaite et al., 2014). One explanation for this gap may be the difficulty in conducting MRI studies with young children. MRI’s high vulnerability to movement artefacts, coupled with the high scan costs, act as the key barriers to conducting imaging research with children. Promisingly, a recent adult study has demonstrated using electroencephalography (EEG), coupled with source reconstruction methods, to mapping brain activity onto the putative DMN (Hsu & Sonuga-Barke, 2016). However, it is unclear whether these methods can be equally successful in developmental studies. Thus, this project aims to establish the feasibility of using source localisation from EEG data to examine the hypothesis that the process of modulating DMN will be important in 4-6-year old children’s ability to switch between recreation and cognitive task. State of Progress: Ongoing Abstract: Evidence from adult studies suggests that mobilising attention after a period of rest requires modulating brain states and physiological activity. The aim of the present study is to examine neural, physiological and behavioural correlates of transitioning from recreational activity to a cognitive task in 4-6-year old children. While having their EEG and heart rate recorded, 90 children will complete three blocks of an AX Continuous Performance Task (AX-CPT). In between the task blocks they will watch a cartoon. Using source reconstruction methods, we will compare neural oscillations localised to the core DMN regions during task and recreation. We will also examine the associations between the DMN and moment-to-moment changes in physiological arousal. Background: Past experimental research investigating the development of children’s attention and cognition has focused on measuring optimal performance during laboratory tasks. However, to function effectively, children need to be able to switch between periods of recreational activity to periods of work (i.e. tasks). This ability might be particularly important for developing school readiness, as children transition from a play-oriented environment, such as preschool or home, to primary school where full engagement during specific periods of work, interspersed with non-work, is necessary. Adult research suggested that efficient switching between rest and task involved successful transitioning between different brain and physiological states. Specifically, the DMN, which is characterised by activity coordinated across a number of sub-regions including medial prefrontal cortex, posterior cingulate, lateral parietal cortex and temporal gyrus (Fox et al., 2005; Fransson, 2005; 7

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Greicius, Krasnow, Reiss, & Menon, 2003; Raichle et al., 2001) may be particularly important in this regard (Sonuga-Barke & Castellanos, 2007). The DMN is active during rest and introspective states but needs to be switched off, so that the other brain networks required for exteroceptive tasks, can get to work (e.g., Raichle & Snyder, 2007; Sidlauskaite et al., 2014). At the same time, the brain needs to mobilise and target its energy to the task and this involves making sure there is a sufficient (but not too excessive) level of arousal to allow effective engagement with the task. A separate strand of research has examined the relationship between physiological arousal and cognitive task performance. Minute-to-minute adaptations in physiological arousal may play an essential role in allowing us to adapt and to respond to changing task demands in different situations (for a review see Thayer, Hansen, Saus-Rose, & Johnsen, 2009). An impaired ability to perform these moment-to-moment adaptations is thought to confer an increased transdiagnostic risk of psychopathology (Beauchaine, 2015; Beauchaine & Thayer, 2015), and has specifically been associated with attention deficit hyperactivity disorder (ADHD; for a discussion see Imeraj et al., 2012). Previous adult research showed associations between indices of physiological arousal and brain activity in the resting networks (Breeden, Siegle, Norr, Gordon, & Vaidya, 2017; Chang et al., 2013; Fan et al., 2012). However, no previous research has systematically investigated the relationship between the DMN and moment-to-moment changes in physiological arousal. Thus, the aim of this novel study is to bring together two different fields to examine DMN activity, arousal and behaviour during switching from freely chosen recreation to task in typically developing children aged 4-6 years – a developmental phase covering the transition to more formal schooling in the UK. Specifically, we aim to answer the following research questions: (1) What are the characteristics of children’s brain activity during recreation and cognitive task? (2) Does neural activity recorded during recreation map onto the DMN regions identified in the adult resting state literature? (3) Are the levels of DMN activity reduced following a transition from recreation to a cognitive task? (4) Does the ability to regulate DMN activity during transitions mature with age? Methods: Participants: Ninety typically developing children aged 4-6years. Design: This study will adopt a 3 (age: 4, 5 and 6 years) × 2 (activity: recreation, task) mixed factorial

design. The dependent variables will be accuracy and response times on the AX-CPT, EEG power and phase coherence and heart rate.

Tasks: We will use an adapted version of an AX-CPT (Chatham, Frank, & Munakata, 2009). This task

presents a series of cartoon images and objects on a computer screen and children are required to pair these according to the rules provided by an experimenter. We will also use two popular children’s cartoons. Procedure: Participants will concurrently have ECG and EEG and recorded while they complete a

20-minute test battery. The entire session will take approximately 1 hour including preparation time. Before the testing commences, we will obtain parents’ consent and children’s assent and they will be able to pause or quit the session at any time. Each session will be video recorded. Funding: This work is funded by a grant awarded to Prof Sonuga-Barke from King’s College London to support the start-up of his research. Publication: Pending

Children’s Development and Neuroplasticity

Neuroimaging and the brain plasticity

Investigators: Prof Katya Rubia1 and collaborators. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: We are interested in both “positive” and “negative” brain plasticity. We have recently completed a study which investigated the negative effects of childhood physical abuse on brain plasticity in adolescents. With respect to positive neuroplastic effects, we collaborate with the Universities of La Laguna and Madrid, Spain, to investigate the effects of Meditation on the structure, function and functional and structural connectivity of the brain. In collaboration with Zürich and Vienna Universities, we will investigate the effects of music training in normal school-children as well as in musically exceptionally talented children (Vienna Boys Choir) on cognition, brain structure and brain function. Please see the following project summaries for further details: • • •

The neurophysiological correlates of physical childhood abuse (page 9) Effects of meditation on brain structure and function (page 12) Effects of singing training on cognition, brain structure and function (page 13)

The neurophysiological correlates of physical childhood abuse

Investigators: Prof Katya Rubia1, Dr Heledd Hart1, Dr Lena Lim1, Dr Kah Mirza1 & Prof Mitul Mehta2. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL. Lay Summary: We investigated the effects of childhood physical maltreatment on brain function, brain structure and structural and functional interconnectivity. Brain abnormalities have been observed in children with early maltreatment. However, no studies have measured functional and structural imaging data within one study or have controlled for comorbid psychiatric conditions, which are typically high in adolescents with physical abuse. In this study, we compared children with physical maltreatment, with similar psychiatric problems but no maltreatment and healthy controls in structural and functional MRI. In addition, we also tested for gene by imaging interactions using specific candidate genes that have been associated with greater susceptibility to the negative effects of maltreatment. We found that childhood physical abuse is associated with significant abnormalities in structural and functional systems of cognition and affect control and that this is specific to the abuse history and not to comorbid psychiatric conditions and correlated with the length of abuse. Furthermore, the effects were exacerbated in people with certain genotypes, suggesting that genes can moderate the effects of childhood physical abuse. State of Progress: Completed

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Abstract: Background: This project explored structural and functional brain abnormalities associated with childhood maltreatment in young male adolescents aged between 12 and 20 years, controlling for psychiatric comorbidities. As a secondary aim, we also obtained information about candidate genes that have previously been associated with susceptibility to adverse environmental effects from cheek swabs taken from the saliva to inform us whether there is an association between these candidate genes (MAO-A and SERT) and abnormal brain structure and function in relation to physical abuse. This will tell us whether genetic predisposition is associated with abnormal brain changes after abuse. Methods: Seventy boys and girls with either (1) childhood abuse alone, (2) childhood abuse and comorbid conditions, and (3) a healthy psychiatric control group, participated. They were aged 12-20 years with an IQ higher than 80. Patients, controls and abuse subjects were identified within SLaM clinics, from the Kids Company and through advertisements. They underwent scans of structural and functional magnetic resonance imaging (MRI), including diffusion tensor imaging. During these scans, they completed 3 tasks (Sustained Attention, Motor Inhibition and Emotion Processing) on which they are typically impaired at. DNA was also collected for gene-imaging interaction analyses. Brain structure and function was compared between these different groups. Meta-analyses were also conducted of all the published structural MRI and white matter tract studies in people with childhood abuse. Results: The findings of the study show that physical childhood abuse is associated with significant changes in the structure and function of the brain. In brain structure, we found widespread alterations in the volume and cortical thickness of several brain regions including orbital and other frontal, parietal, temporal, insular and cerebellar regions. In brain function, we found that children with childhood abuse have increased activity and abnormal functional connectivity in frontal regions of error monitoring (presumably due to a hypersensitivity to errors due to harsh punishing) and in fronto-limbic regions of fear processing as well as reduced activation and connectivity in fronto-parietal regions of attention. We furthermore found that the structural and functional deficits were exacerbated in people with specific genotypes, suggesting that genes can moderate the effect of childhood physical abuse. Most deficit findings were specific to the abuse as they were not observed in the psychiatric control group and were associated with the abuse duration. The diffusion tensor imaging study showed that childhood abuse is associated with reduced structural integrity of neural pathways connecting the frontal, temporal and occipital cortices that are known to mediate affect and cognitive control. The meta-analyses showed that childhood physical abuse is associated with consistent deficits in frontal and limbic areas that are part of cognitive and affective systems as well as with white matter tracts that connect frontal regions with posterior and limbic regions that form networks of attention, cognition and of emotion control. Conclusion: The findings show that childhood physical abuse is associated with significant structural, functional and functional and structural connectivity abnormalities in several cortical and subcortical systems associated with cognitive functions such as attention and error processing, and with emotion control such as fear processing and that this is specific to the abuse and not due to the comorbid psychiatric conditions associated with the abuse. The findings, together with our meta-analyses show that childhood physical abuse is associated with significant abnormalities in the structure, function and structural and functional connectivity of the brain.

Children’s Development and Neuroplasticity

Funding: Kids Company, Reta Lila Weston Foundation for Medical Research and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and King’s College London. Figure 1. Anatomical and schematic representation of brain regions and networks implicated in childhood maltreatment based on structural and functional imaging studies.

Fronto-limbic areas (pink) are involved in emotion and motivation processing and frontostriatal brain (blue) regions involved in executive functions, working memory, inhibition and attention. Panel (A) shows an axial view containing the basal ganglia. Panels (B) and (C) are sagittal views highlighting the hippocampus, amygdala and DLPFC and ACC, OFC, and cerebellum, respectively. Panels (D) and (E) show the schematic representation of the fronto-limbic and fronto-striatal networks associated with childhood abuse. Adapted from Hart & Rubia (2012).

Publications: 1.

Hart H & Rubia, K. (2012). Neuroimaging of child abuse: A critical review. Frontiers in Human Neuroscience, 6:52. 2. Lim L, Radua Q & Rubia K. (2014). Gray matter abnormalities in childhood maltreatment: A voxel-wise meta–analysis. American Journal of Psychiatry, 171(8):854-863 3. Lim L, Hart H, Mehta M, Mirza K & Rubia K. (2015). Neural correlates of error processing in young people with a history of severe childhood abuse: An fMRI study. American Journal of Psychiatry, 17:1-12 4. Lim L, Hart H, Mehta MA, Simmons A, Mirza K & Rubia K. (2016). Neurofunctional abnormalities during sustained attention in severe childhood abuse. PLoS One, 11(11):e0165547. 5. Lim L, Hart, H, Worker A, Mehta MA, Simmons A, Mirza K & Rubia K. (2017). Grey

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matter volume and thickness abnormalities in young people with a history of childhood abuse. Psychological Medicine, 10, 1-13. 6. Hart, H, Lim L, Mehta M, Chatzieffraimidou A, Curtis C, Xiaohui X, Breen G, Simmons A, Mirza K & Rubia K. (2017). Reduced functional connectivity of frontoparietal sustained attention networks in severe childhood abuse. PLOS ONE, 12(11): 1-17. 7. Hart H, Lim L, Mehta M, Curtis C, Xu X , Breen G, Simmons A, Mirza K & Rubia K. (2018). Altered functional connectivity of fronto-cingulo-striatal circuits during error monitoring in adolescents with a history of childhood abuse. Frontiers in Human Neuroscience, 12(7): 1-14. 8. Hart H, Lim L, Mehta MA, Simmons A, Mirza K & Rubia K. (2018). Altered fear processing in adolescents with a history of severe childhood maltreatment: An fMRI study. Psychological Medicine, 12:1-10 9. Lim L, Hart H, Howells H, Mehta MA, Simmons A, Mirza K, Rubia K. (2018). Reduced white matter tract integrity in young people exposed to childhood abuse. In preparation.

Effects of meditation on brain structure and function

Investigators: Prof Katya Rubia1, Dr Sergio Hernandez2, Prof Jose-Luis Gonzalez-Mora2 & Dr Alfonso Barros-Loscertales3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Universidad de La Laguna, Spain; 3 Universitat Jaume I de CastellĂłn, Spain.

Lay summary: In collaboration with the Universities of La Laguna and Madrid we have conducted several studies investigating the effects of Meditation on brain structure and function. We found that long-term Meditation of more than 5 years has a positive effect on brain regions of attention and affect control. At a functional level, meditation increases the activation of regions of attention and self-control and increases the functional connectivity of top-down cognitive control and affect control regions. At a structural level, meditation is associated with larger structures of lateral frontal regions of attention and self-control and of fronto-limbic regions of affect control. State of Progress: Completed Abstract: Background: Meditation has been shown to have preventative and therapeutic health benefits. In collaboration with the Universities of La Laguna and Jaume de Castellon, Spain, we conducted several studies investigating the effects of Meditation on brain structure, function and functional connectivity. We were particularly interested in the state of mental silence which has been associated with the health benefits of Meditation and which is taught by some Meditation techniques.

Methods: Twenty-three long-term Meditators of more than 5-year experience of Sahaja Yoga Meditation and 23 healthy controls who never meditated before matched on age, gender, height, body-mass index and education participated in 3 separate MRI studies on a 3T scanner in La Laguna University. In the functional MRI study, Meditators had to try to achieve the state of mental silence in the MRI scanner, alternated with a resting state. For structural MRI, we acquired voxel based morphometry data. To test the correlation between the depth of mental silence and structure and functional connectivity data, we tested first, which structural regions in the brain were associated with the depth of mental silence subjectively achieved in the MRI scanner and tested for functional connectivity between the resulting region and other brain regions. Diffusion tensor imaging data have also been acquired.

Children’s Development and Neuroplasticity

Results: At a functional level, meditation increases the activation of regions of attention and self-control, in particular of right inferior frontal and superior temporal regions. At a structural level, long-term meditation was associated with larger grey matter of lateral frontal regions of attention and self-control and of fronto-limbic regions of affect control. The known association between age and grey matter loss was more pronounced in healthy controls, although this was short of significance. The functional connectivity study showed that the state of mental silence is associated with larger grey matter volume in the anterior cingulate gyrus, and with increased functional connectivity between this region and insula and putamen. Conclusions: Long-term Meditation that teaches the state of mental silence has a positive effect on brain regions that are crucial for top-down regulation of affect and cognition. Functionally, it appears to enhance right frontal and temporal regions of attention control. Structurally it is associated with larger structure of regions of top-down cognitive and affective control. Furthermore, the depth of the state of mental silence is associated with increased functional connectivity between the anterior cingulate and regions that are important for interoception, emotion and attention regulation, suggesting increased top-down control of cognitive and emotional networks. Funding: Universidad de La Laguna Publications: 1.

Hernandez, SE, Suero J, Rubia K & González-Mora JL. (2015). Monitoring the neural activity of the state of mental silence while practicing Sahaja Yoga meditation. The Journal of Alternative and Complementary Medicine, 21(3): 175-179. Hernandez, SE, Suero J, Barroso A & Rubia, K. (2016). A voxel-based morphometry study on brain structural changes associated with long-term Sahaja Yoga meditation. PLOS ONE, 11(3): e0150757. Hernández SE, Barros-Loscertales A, Xiao Y, González-Mora JL & Rubia K. (2018). Gray matter and functional connectivity in anterior cingulate cortex are associated with the state of mental silence during Sahaja Yoga meditation. Neuroscience, 371: 395-406

Effects of singing training on brain structure, function and cognition

Investigators: Prof Katya Rubia1, Prof Lutz Jäncke2 & Prof Erich Vanecek3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Psychology, University of Zürich, Switzerland; 3 Department of Psychology, University of Vienna, Austria.

Lay Summary: In collaboration with the Universities of Zürich and Vienna, funded by the Music Pedagogic Research Centre, Switzerland, we will investigate the effects of 1-year music training on cognitive functions, brain structure and brain function in normal school children as well as in musically talented children of the Vienna Boys Choir. We will also investigate the effects of talent on the brain plastic effects of music training. State of Progress: The study will commence in January 2019. 13

CAMHS CAG Projects Day 2018

Abstract: Background: In this project, we plan to examine the influence of music tutoring (in particular singing tutoring) on cognition, neuroanatomy, and neurophysiology in a relatively large sample of children (age range 8-14 years) characterized by different musical backgrounds. Most previous studies in this research area have used cross-sectional approaches comparing children with and without music training mitigating causal inferences of music tutoring on the above-mentioned measures. Methods: We will conduct a longitudinal study (1-year duration) with children from the Vienna Boys Choir (VBC), a world-renown boy choir comprising pre-selected children (based on suspected musical talent), enrolled in a specialized school with regular schooling, and 4-6 hours per day singing rehearsals using the Wirth-Method. In addition, we will work with children from the SUPERAR project comprising mostly “music-naive” (unselected) children receiving intensive musical tutoring on a regular basis. As third sample, we work with children of average socioeconomic status receiving no music lessons (NOMUSIC). In order to delineate the cognitive, neurophysiological, and neuroanatomical aspects contributing to what can be seen and interpreted as “talent” for music performance and here choir singing we will extend the study duration for the VBC children to 4 years in order to gain more measurement time points for the longitudinal analysis (this will be study 2). We anticipate that we can “predict” inter-individual differences in music and singing skills after four years of music tutoring on the basis of cognitive, social, and neural measures obtained at baseline. Anticipated results and conclusion: We anticipate obtaining (for the first time) detailed information about the causal influence of music interventions on brain anatomy, function, and cognition in children on a large sample at the age of 6-10 years. In addition, we will be in the position to identify the anatomical, functional, or cognitive predictors of improvements in terms of singing and music performance especially for the VBC children. Thus, we will be able to operationalize “talent”. By identifying the possible predictors of superior musical and singing performance we hope to improve and/or optimize future musical “talent” selection. Taken together, this will be the first well-designed large-scale longitudinal study on music interventions in children. The availability of study samples such as the SUPERAR or VBC is unique in the world to study the effects of choir training on brain anatomy, brain function, and the associated cognition and hence the outcome of the study will be unprecedented. Funding: Music Pedagogic Research Centre, Switzerland.

Childrenâ&#x20AC;&#x2122;s Development and Neuroplasticity

Neurodevelopmental Disorders

CAMHS CAG Projects Day 2018

British study of infant siblings (BASIS)

Investigators: Prof Tony Charman1, Prof. Andrew Pickles2, Prof Mark Johnson3 & Dr Emily Jones3 1 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Biostatistics and Health Informatics , IoPPN, KCL; 3 Centre for Brain and Cognitive Development, School of Psychology, Birkbeck, University of London.

Lay Summary: The British Autism Study of Infant Siblings (BASIS) is a collaborative research network for the study of infants at familial risk for autism. The primary aim of BASIS is to provide a platform for the study of infants at risk for autism in the UK and to facilitate collaborative links between scientists working in the area in Europe and internationally. Using newly developed techniques for studying brain and behaviour in infants, BASIS scientists investigate whether there are any differences in development between infants who have brothers or sisters with autism and those who do not. In the long term, this will help identify the early signs of the disorder, allowing for earlier and more effective intervention aimed at improving the quality of life of children with autism. State of Progress: Ongoing Abstract: Background: Infants at familial risk of autism by dint of having an older brother or sister with a diagnosis have a ~20% chance of going on to have autism themselves and also elevated rates of other atypical outcomes including language and developmental delays, the ‘broader autism phenotype’, anxiety and ADHD. Methods: We study infants from before 6 months of age using a combination of experimental (NIRS, EEG, eyetracking, electrophysiology) and behavioural methods and subsequently follow them up in sequential assessments at 12, 24 and 36 months of age and then into mid-childhood (7 years). Results: We have reported a number of predictors of a later diagnosis of autism from as early as 12 months and even 6 months of age. These include social (e.g. neural responses to gaze) and non-social (e.g. pupillary light reflex, attention disengagement) neurocognitive processes. We are currently examining infant predictors of mid-childhood outcomes. Conclusion: We have been able to identify early predictors of later outcomes and have developed and are testing interventions that may improve outcomes in infants at familial risk of autism and ADHD. Funding: Medical Research Council, Horizon 2020, IMI2, NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Publications: Recent publications (from >50): 1.

Nyström P, Gliga T, Nilsson Jobs E, Gredebäck G, Charman T, Johnson MH, Bölte S, The BASIS team, The EASE team & Falck-Ytter T. (2018). Enhanced pupillary light reflex in infancy is associated with autism diagnosis at three years of age. Nature Communications, 9:1678.

Neurodevelopmental Disorders

2. 3. 4.

5. 6. 7. 8.

9. 10. 11. 12.

Doherty B, Charman T, Johnson MH, Scerif G, Gliga T & the BASIS Team (2018). Visual search in the broader autism phenotype: what young children search for and cooccurring ADHD symptoms matter. Developmental Science, e12661. Lloyd-Fox S, Blasi A, Pasco G, Gliga T, Elwell CE, Charman T, Murphy D, Johnson MH & The BASIS Team. (2018). Neural signature of autism evident before six months of life. European Journal of Neuroscience, 47736-749. Vernetti A, Charman T, Gliga T, Senju A, Johnson MH & the BASIS Team. (2018). Simulating interaction: Using gaze-contingent eye-tracking to measure the reward value of social signals in toddlers with and without autism. Developmental Cognitive Neuroscience, 29:21-29. Cheung HMC, Bedford R, Johnson MH, Charman T, Gliga T & the BASIS Team. (2018). Visual search performance in infants links to later ASD diagnosis. Developmental Cognitive Neuroscience, 29:4-10. Hendry A, Jones EJH, Bedford B, Gliga T, Charman T, Johnson MH & the BASIS Team. (2018). Developmental change in look durations predicts later effortful control in toddlers at familial risk for ASD. Journal of Neurodevelopmental Disorders, 10:e3. Kolesnik A, Jones EJH, Garg S, Green J, Charman T, Johnson MH & The EDEN and BASIS Teams (2017). Early development of infants with Neurofibromatosis Type 1: A case series. Molecular Autism, 8:e62. Green J, Pickles A, Bedford R, Pasco G, Cheung CMH, Wan MW, Gliga T, Jones EJH, Slonims V, Charman T & Johnson MH. (2017). Randomised trial of a parent-mediated intervention for infants at high risk for autism: Longitudinal outcomes to age three years. Journal of Child Psychology and Psychiatry, 58:1330-1340. Milosavljevic B, Shephard E, Happé F, Johnson MJ, Charman T & The BASIS Team. (2017). Anxiety and attentional bias to threat in children at increased familial risk for autism spectrum disorder. Journal of Autism and Developmental Disorders, 47:3714-3727. Bedford R, Gliga T, Shephard E, Jones EJH, Elsabbagh M, Pickles A, Charman T & Johnson MH. (2017). Neurocognitive and observational markers: Prediction of autism spectrum disorder from infancy to mid-childhood. Molecular Autism, 8:e49. Shephard E, Milosavljevic B, Pasco G, Jones EJH, Gliga T, Happé F, Johnson MJ, Charman T & The BASIS Team. (2017). Mid-childhood outcomes of infant siblings at familial high-risk of autism spectrum disorder. Autism Research, 10:546-557. Charman T, Young GS, Brian J, … & Zwaigenbaum L. (2017) Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A Baby Siblings Research Consortium (BSRC) study. Autism Research, 10:169-178.

Improving outcomes for people with autism spectrum disorders by reducing mental health problems

Investigators: Prof Emily Simonoff1 (chief investigator), Prof Gillian Baird2, Prof Bryony Beresford3, Prof Tony Charman4, Prof Martin Knapp5, Prof Declan Murphy6,7, Prof Andrew Pickles8, Carol Povey9, Prof Paramala Santosh1, Prof Stephen Scott1 & Dr Vicky Slonims10 (senior investigators) 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Guy’s and St Thomas’ NHS Foundation Trust, King’s Health Partners; 3 Social Policy Research Unit, University of York; 4 Department of Psychology, IoPPN, KCL; 5 Department of Social Policy, London School of Economics and Political Science; 6 Sackler Institute for Translational Neurodevelopment, IoPPN, KCL; 7 Department of Forensic and Neurodevelopmental Sciences, IoPPN, KCL; 8 Department of Biostatistics and Health Informatics, IoPPN, KCL; 9 Centre for Autism, National Autistic Society; 10 Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London.

CAMHS CAG Projects Day 2018

Lay Summary: Autism spectrum disorders (ASDs) involve impairments in the areas of reciprocal social interaction and communication, alongside repetitive behaviours and interests. ASDs are common, occurring in ~1% of the population, lifelong and can be severely impairing for the individual and family. They can also be hugely expensive, costing the UK more than ÂŁ28 billion annually in care and lost opportunity. The evidence base for treatments focusing on core ASD symptoms is small. Previous research and consultation with users found that the greatest impact often comes from the commonly associated mental health problems, such as anxiety. The most severe problems include serious aggression directed at self and/or others and severe disruptive and non-compliant behaviour, these lead to exclusion from everyday family, educational and community activities, poor quality of life and increased family stress. This programme focuses on decreasing severe mental health and behavioural problems as a strategy for improving outcomes for people with ASD and their families. The programme comprises four linked work packages (WPs): WP1, Measurement: Develops and validates a questionnaire to assess and guide intervention for additional

mental health/behavioural problems in ASD. WP2, Biographies: Obtains qualitative accounts from young people with ASD, and parents, regarding

their experiences of identifying mental health problems and obtaining/using services for these. WP3, Predictors: Identifies the early predictors for later mental health/behavioural problems. WP4, Treatment: Develops and evaluates a parent-based intervention to reduce emotional and

behavioural problems in young children with ASD. Patient Public Involvement (PPI): Two PPI groups, one comprised of adults with ASD and another with

parents of children with ASD are acting in an advisory role for the development of the IAMHealth programme. State of Progress: Ongoing Abstract: Background: A substantial group of young people with ASD will experience significant difficulties with their behaviour, which cause considerable distress for the person with ASD, their families and carers and impact on their ability to take part in community activities. Exactly how these behavioural problems are linked to common mental health conditions that are common in this population, such as ADHD, anxiety and oppositional defiant disorder, is unclear. This project uses a multi-method approach to understand the causes and impact of these additional problems, as well as to develop and evaluate clinical assessment and treatment tools in order ultimately to improve services. Methods: WP1, Measurement: The Assessment of Concerning Behaviour (ACB) questionnaire was developed following a comprehensive literature review and consultation focus groups with professionals, service users and their parents/carers. Patient and parent/carer versions have been developed and considered with respect to the face and content validity of the items, readability and clarity of completion. Pilot questionnaires were tested for acceptability by a sample of 30 participants, which included patients from South London and Maudsley NHS Foundation and local community clinics. Following the piloting stage, the questionnaire was re-drafted. The recruitment phase is ongoing and, thus far, the questionnaires have been completed by 242 parents and 151 children and young people to establish the toolâ&#x20AC;&#x2122;s psychometric properties and clinical utility. WP2, Biographies: A qualitative approach was employed capturing the accounts, views and experiences of

young people with ASD (aged 22-25 years) who have developed mental health and severe behavioural problems and parents of children and young people (aged 11-15 and 22-25 years). 18

Neurodevelopmental Disorders

WP3, Predictors: A longitudinal approach was employed to identify early risk and protective factors for

developing mental health/ behavioural problems. The QUEST cohort is a community-based sample of 277 families from Lewisham and Bromley. All families in the study had a child diagnosed with ASD born between September 2000 and September 2004. The participants were first seen at aged 4-9 years when autism severity, IQ and mental health problems were assessed. Two further waves of the QUEST study were funded as part of the IAMHealth Study. At age 11-15 years, their parents answered a series of further questionnaires about the child’s emotions and behaviour (including Strengths and Difficulties Questionnaire [SDQ]), autism symptomology (Social Communication Questionnaire [SCQ]) and parenting and home environment. The families also provided a five-minute speech sample (FMSS), participated in a parent-child interaction task and the children completed cognitive tasks combined with recording of neural activity. Currently, at age 13-17 years, the participants are being seen again to assess their mental health outcomes (using the Child and Adolescent Psychiatric Assessment [CAPA]) and questionnaires (including SDQ). WP4, Treatment: The Autism Spectrum Treat and Resilience (ASTAR) project is a feasibility study

and pilot randomised controlled trial (RCT) of two newly developed group-based parent-focused interventions for parents of young children with ASD. It compares a parent training intervention to an active control parent information-focused intervention to test the specific effect on reducing concerning behaviours and emotions. Measures of parent-child interactions, parent- rated child emotions and behaviours, parental experiences and stress, and use of services and costs are obtained at baseline and immediately after the intervention. The feasibility study is complete and feedback from families was used to modify the interventions and research procedures prior to commencing the pilot RCT in late 2017. The pilot RCT is ongoing and will be completed in early 2019. Results and conclusion: Please see the following project summaries for further details: • Developing an observational coding scheme for parent-child interaction in autism spectrum disorder. (Page 20) • Understanding the relationship between parental expressed emotion and the development/ maintenance of additional psychopathology in young people with ASD. (Page 22) • Exploring the neurocognitive and electrophysiological correlates of emotional and behavioural problems in young people with autism spectrum disorder. (Page 24) • Development of the observation schedule for children with autism spectrum disorders– anxiety and behaviour (OSCA-AB): A new measure of parent and child behaviour for use with children with ASD. (Page 27) • Can a parent-focused intervention reduce emotional and behavioural problems in young children with ASD? The autism spectrum treatment and resilience (ASTAR) feasibility and pilot trial. (Page 148) • Predictive Parenting: Developing a new group parent intervention for behavioural and emotional problems in children with ASD. (Page 149) Funding: The IAMHealth programme is funded by the National Institute for Health Research (NIHR) as a Programme Grant for Applied Research (RP-PG-1211-20016). Publications: 1.

2. 3.

Carter Leno VC, Chandler S, White P, Pickles A, Baird G, Hobson C, ... Simonoff E. (2017). Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD. European Child & Adolescent Psychiatry, 1-10. Carter Leno VC, Charman T, Pickles A, Jones CRG, Baird G, Happé F & Simonoff E. (2015). Callous–unemotional traits in adolescents with autism spectrum disorder. British Journal of Psychiatry, 207(5):392-399. Chandler S, Howlin P, Simonoff E, Kennedy J & Baird G. (2016). Comparison of parental

CAMHS CAG Projects Day 2018

estimate of developmental age with measured IQ in children with neurodevelopmental disorders. Child: Care, Health and Development, 42(4):486-493. 4. Chandler S, Howlin P, Simonoff E, O’Sullivan T, Tseng E, Kennedy J, … Baird G. (2015). Emotional and behavioural problems in young children with autism spectrum disorder. Developmental Medicine & Child Neurology, 58(2):202-208. 5. Coleman-Fountain E. (2017). Uneasy encounters: Youth, social (dis)comfort and the autistic self. Social Science and Medicine, 185:9-16. 6. Coleman-Fountain E., & Beresford B. (in press). Engaging young adults with autism in discussions around mental health. In Hujala A, Laulainen S, Thomas W & McMurray R. (eds). The challenge of wicked problems in health and social care: An international text. Routledge. 7. Milosavljevic B, Carter Leno VC, Simonoff E, Baird G, Pickles A, Jones CRG, ... Happé F. (2016). Alexithymia in adolescents with autism spectrum disorder: Its relationship to internalising difficulties, sensory modulation and social cognition. Journal of Autism and Developmental Disorders, 46(4):1354-1367. doi:10.1007/s10803-015-2670-8. 8. Romero-Gonzalez M, Chandler S & Simonoff E. (2018). The relationship of parental expressed emotion to co-occurring psychopathology in individuals with autism spectrum disorder: A systematic review. Research in Developmental Disabilities, 72:152-165. 9. Salazar F, Baird G, Chandler S, Tseng E, O’Sullivan T, Howlin P, ... Simonoff E. (2015). Co-occurring psychiatric disorders in preschool and elementary school-aged children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 45(8):22832294. doi:10.1007/s10803-015-2361-5. 10. Santosh P, Tarver J, Gibbons F, Vitoratou S & Simonoff E. (2016). Protocol for the development and validation of a questionnaire to assess concerning behaviours and mental health in individuals with autism spectrum disorders: The Assessment of Concerning Behaviour (ACB) Scale. BMJ Open, 6(3). doi:10.1136/bmjopen-2015-010693.

Developing an observational coding scheme for parentchild interaction in autism spectrum disorder

Investigators: Isabel Yorke1, Pippa White1, Dr Virginia Carter Leno1, Dr Susie Chandler1, Prof Tony Charman2 & Prof Emily Simonoff1. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Psychology IoPPN, KCL.

Lay Summary: Additional emotional and behavioural problems (EBP) are very common in children and young people with autism spectrum disorder (ASD) and are a source of particular difficulty and unmet need for individuals and their families. One of the aims of the IAMHealth research programme is to identify predictors of the development and maintenance of such EBP. One set of predictors that has been well established in the general population is the family social environment, including parent psychological wellbeing and parenting behaviour. Parents of children with ASD experience particularly high levels of psychological distress, which may affect everyday interactions between parents and children and make dealing with challenging child behaviour more difficult. Existing research on these associations is primarily based on parent questionnaire report of their own stress levels, mental health and behaviour, as well as their children’s EBP, which may introduce shared rating effects. We therefore aimed to develop an alternative method of directly investigating elements of parent and child behaviour during a collaborative Parent-Child Interaction (PCI) task. We used a task and observational coding scheme previously employed in general population research. Our aims were to check the suitability of the task for adolescents with ASD and to assess the ability of the coding scheme to reliably pick up variability across participating parent-child dyads. We found that the task was suitable for the majority of participants; however, those at lower levels of development could not access the task in the intended 20

Neurodevelopmental Disorders

manner and an alternative task was required. The ultimate aim is to develop and validate tasks that can be applied in clinical and research settings to characterise parent-child relationships. State of Progress: Ongoing Abstract: Background: Children and young people with ASD are highly likely to meet criteria for additional psychopathology, which is often the source of considerable distress for individuals and their families. One aim of the IAMHealth project is to identify risk and protective factors which account for variability in symptom severity. According to research in the general population, elements of family social environment, e.g. parents’ stress, mental health and behaviour may predict severity of child EBP. Parents of children with ASD experience psychological distress at higher rates than parents of typically developing children, and those with physical disabilities. This may disrupt parent-child relationships and compromise parents’ ability to deal with challenging child behaviour effectively, which may contribute to the maintenance of child EBP. In order to investigate these putative associations, it is important to use reliable and valid measures; however, most existing research relies upon parent-report questionnaires about own stress levels, mental health and behaviour, as well as their children’s EBP. Such measures may have low ecological validity and use of a single informant may inflate associations between them. We therefore wished to investigate elements of parent and child behaviour during a collaborative PCI task, using an observational coding scheme. Our aims were to (a) check suitability of the task for teenagers with ASD; (b) establish inter-rater reliability in coding the interactions; (c) assess the ability of the coding scheme to detect variability across participating parent-child dyads in the elements coded. Methods: Participants came from the QUEST cohort, a well-characterised sample of children with ASD and their caregivers. At the second wave of data collection (child age 11-15 years), a subset of participants (N=71) participated in a videotaped PCI activity. Each parent-child dyad was asked to complete two collaborative tasks with clearly-defined roles for the parent and for the child. One of these was the Etch-a-Sketch (EAS) task. The parent and child were each assigned a separate control on the EAS toy and asked to draw a house together (Fig. 2). Videos were transcribed and rated using the GESU coding scheme, previously used in general population research with young children. The original GESU comprises 16 scales upon which various aspects of child and parent behaviour, and emergent properties of the interaction are rated. Among these are parent verbal and physical control behaviours, praise and criticism of the child, and social engagement with the child. Rated child behaviours include persistence in completing the task and social engagement with the parent. The overall atmosphere (considering harmony and conflict) is also rated. In order to establish inter-rater reliability, 30 randomly selected videos were to be rated by both IY and PW. Results: In 53 out of 66 codable interactions (80%), the child was considered to have the cognitive and motor skills necessary to access the EAS task. For those that did not, an alternative task was devised and piloted as a sub-component of this project. Weighted kappa was calculated to assess inter-rater reliability. Three scales showed no variance across participants or raters. Ten scales showed good reliability (kappa ≥ .7) and six showed fair reliability (.5 ≤ kappa < .7). One scale showed poor reliability (kappa < .5). Average kappa was .73 across all variable scales. Most scales showed some degree of variability across all videos that have been coded by consensus or IY alone (N=48). However, instances of parent rough physical handling of the child, and parent praise or criticism of their child’s characteristics were very rare. Other codes showed a wider range of scores; however, many showed positive or negative skew. 21

CAMHS CAG Projects Day 2018

Conclusion: The EAS task is appropriate for most adolescents with ASD and their parents; however, a substantial proportion could not access the task. Overall, good inter-rater reliability was established across codes of the GESU coding scheme. However, certain scales fail to detect variability across dyads. The next step in this project will be to investigate the factor structure of the coding scheme, with the eventual aim of assessing associations of elements of PCI with other variables of interest, e.g. child EBP and parent psychological distress. Funding: IY was supported by a PhD studentship funded jointly by Autistica and the Sackler Institute. The QUEST Follow-up Study is part of the IAMHealth programme, funded by the NIHR. Publications: Pending Figure 2. The Etch-a-Sketch toy and task.

The parent and child were each assigned a separate control on the EAS toy and asked to draw a house together

Understanding the relationship between parental expressed emotion and the development/maintenance of additional psychopathology in young people with ASD

Investigators: Prof Emily Simonoff1, Prof Tony Charman2, Dr Susie Chandler1, Pippa White1, Isabel Yorke1, Dr Virginia Carter Leno1 & Dr Marina Romero Gonzalez1. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Psychology IoPPN, KCL.

Lay Summary: Young people with autism spectrum disorder (ASD) commonly experience emotional and behavioural problems over and above their ASD symptoms; around 70% meet criteria for an additional diagnosis (e.g., an anxiety disorder, ADHD, oppositional defiant/conduct disorder). Understanding the factors that might influence the course of these additional problems could help us identify targets for intervention. Expressed emotion (EE) describes the affective relationship between two people, commonly parent and child. Several components are included: criticism, emotional warmth and the quality of the relationship. High EE demotes the negative componets (critical comments, lack of 22

Neurodevelopmental Disorders

warmth and a negative relationship) and is a recognised risk factor for poor mental health in nonASD populations. However, little is known about the relationship between EE and mental health in individuals with ASD. This study examined associations between parental EE and emotional/ behavioural problems in 11-15 year-olds with ASD. Parents were asked to speak about their child and how the two of them got along, for 5 minutes. They also completed questionnaires about their childâ&#x20AC;&#x2122;s behaviours and emotions. We found high levels of parental EE were associated with behavioural problems such as conduct and hyperactivity, even when other child and parental factors (e.g., childâ&#x20AC;&#x2122;s IQ, ASD severity, parental stress and self-efficacy) were taken into account. No association was found between EE and emotional problems. The link between high parental EE and behaviour problems is consistent with previous studies. However, further research, following families over time, is required to properly understand the causes and consequences of high EE on the mental health of young people with ASD. State of Progress: Cross-sectional study complete, longitudinal study ongoing Abstract: Background: Previous studies have found high rates of co-occurring psychopathology in children and young people with autism spectrum disorder (ASD), with around 70% meeting criteria for an additional psychiatric disorder. Understanding the risk and protective factors that may influence the course of co-occurring psychiatric disorders in ASD may therefore provide targets for intervention. In individuals without ASD but other mental health conditions, research has explored the affective relationship between individuals and their parents/carers: expressed emotion (EE). EE describes the affective relationship between two people, and has been found to be a significant risk marker for poor mental health outcomes in non-ASD samples. Currently, little is known about relationship between EE and the development of additional psychopathology in ASD. Early studies suggest that the relationship is likely to be complex and potentially bi-directional. This study has two parts: a cross-sectional study that explores associations between parental EE and levels of emotional and behavioural problems in young people with ASD; and a longitudinal study that seeks to understand the causal role of EE predicting subsequent psychopathology or vice versa. Methods: A community-based sample of 78 families participated in the cross-sectional study. The young people (44 male, 34 female) were aged 11-15 years old at assessment, and all had a diagnosis of ASD. EE was assessed using the Autism Specific Five Minute Speech Sample (ASFMSS), which generates an total score, and category (high, borderline, low), as well as scores for each of its components (e.g., warmth, relationship, emotional over-involvement, critical/positive comments). Autism severity was assessed with the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and the Social Communication Questionnaire (SCQ). Parents also completed the Strengths and Difficulties Questionnaire (SDQ), Developmental Behavior Checklist (DBC), Kessler Psychological Distress Scale (K-10), Autism Parenting Stress Index (APSI), Brief Parental Self-Efficacy Scale (BPSES) and a demographic questionnaire. Cognitive abilities were assessed using standardised assessments. Associations between EE, additional psychopathology (indexed by SDQ and DBC subscale scores), and additional parental factors were examined through correlational analyses, followed by multivariate regressions. In the longitudinal study, we plan to use data from three time-points (ages 4-9, 11-15, and 13-17 years) to explore the causal relationship between EE and the course of co-occurring psychopathology in the same ASD sample.

CAMHS CAG Projects Day 2018

Results: Within this cross-sectional study, significant correlations were found between high levels of EE and externalising behaviours, specifically SDQ conduct scores, DBC disruptive and hyperactivity scores. The significant association between EE and DBC disruptive and hyperactivity scores remained when IQ, autism severity, parental stress and self-efficacy were controlled for. No significant associations were found between EE and internalising problems as indexed by SDQ emotion scores or DBC anxiety or depression scores. Conclusion: The finding that high levels of parental EE are associated with increased behavioural/ externalising problems is consistent with previous non-ASD studies, and more recently, ASD studies. Thus, young people with ASD living within family environments characterised by high EE and critical comments were reported to have more behaviour problems and hyperactivity than those with living in lower EE families. However, no significant associations were found between EE and emotional or internalising problems. Further research, using longitudinal designs, is required determine the direction of the relationship between parental EE and child psychopathology. This should enable us to fully understand the causes and consequences of high levels of parental EE in young people with ASD. Funding: The QUEST Follow-up Study is part of the IAMHealth programme, funded by the NIHR. In addition, Dr Romero Gonzalez received funding from the Alicia Koplowitz Foundation to work on the study. Publication:

Romero-Gonzalez, M., Chandler, S. & Simonoff, E. (2018). The relationship of parental expressed emotion to co-o ccurring psychopathology in individuals with autism spectrum disorder: A systematic review. Research in Developmental Disabilities, 72:152-165.

Exploring the neurocognitive and electrophysiological correlates of emotional and behavioural problems in young people with autism spectrum disorder

Investigators: Dr Virginia Carter Leno1, Professor Emily Simonoff1, Professor Tony Charman2, Professor Andrew Pickles3, Dr Susie Chandler1, Pippa White1 & Isabel Yorke1. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Psychology IoPPN, KCL 3 Department of Biostatistics and Health Informatics, IoPPN, KCL.

Lay Summary: Young people with autism spectrum disorder (ASD) are characterised by high rates of co-occurring emotional and behavioural problems. These additional difficulties can have a negative impact not only on an individualâ&#x20AC;&#x2122;s quality of life, but also on their participation in the community, their educational achievement, and their family and caregivers. Consultation with caregivers of young people with ASD has identified better understanding of these additional difficulties as a priority area of research. Currently, the drivers of these emotional and behavioural problems in young people with ASD are largely unknown. Certain characteristics may increase the chances of a young person with ASD disorder develops these additional difficulties. One approach is to explore how individual variability in domains of cognitive functioning (e.g., executive functioning, emotion recognition) relates to co24

Neurodevelopmental Disorders

occurring emotional and behavioural problems. Knowing which characteristics are associated with co-occurring emotional and behavioural problems may help us to understand potential risk factors and driving mechanisms, and to develop novel and targeted interventions. State of Progress: Complete. Abstract: Background and Methods: In two well-characterised samples of young people with ASD (SNAP: n=100, age range 14-16, IQ range 50-119; QUEST: n=83, age range 11-15 years, IQ range 19-129), we measured performance on tasks designed to tap into ability in specific cognition domains (e.g., executive functioning, perceptual processing, emotion recognition). In the QUEST sample, selected tasks were also combined with recording of neural activity (using electroencephalography; EEG). In both samples, caregivers completed questionnaires regarding co-occurring emotional and behavioural problems (e.g., the Developmental Behaviour Checklist, the Strengths and Difficulties Questionnaire). IQ was assessed using standardised assessments. First, analyses compared cognitive performance in young people with ASD against not only typically developing individuals (n=43), but also against two other psychiatric groups characterised by behaviour problems; individuals with attention deficit hyperactivity disorder (ADHD; n=21), and individuals with oppositional defiant/conduct disorder (ODD/CD; n=26). Next, analyses tested whether within young people with ASD, variability in functioning in different cognitive domains was associated with additional emotional and behavioural problems. Results: Cognitive functioning in young people with ASD: Using QUEST data, analyses showed young people with

ASD were characterised by impairments in executive functioning (specifically in response inhibition, premature responsiveness and response variability) when compared against both typically developing individuals, but also individuals with ODD/CD, and those with ADHD. This pattern of results remained when we adjusted for between-group differences in age, IQ and sex. Within ASD analyses: (1) Behavioural measures of cognition: In the QUEST sample, poorer behaviourally

measured executive functioning was associated with co-occurring ADHD symptoms (Fig. 3A&B), but not other emotional or behavioural problems. In the SNAP sample, results showed that other cognitive domains were associated with specific types of behaviour problems; poorer theory of mind was associated with increased self-injurious behaviour, whereas poorer perceptual processing was associated with increased externalising behaviours (Fig. 3C). (2) Neural measures of cognition: In the QUEST sample, EEG indices of executive functioning were not related to any co-occurring problems. EEG indices of perceptual processing, specifically hypo-sensitivity to incoming perceptual/ sensory information (as measured by the mismatch negativity wave; MMN), were associated with both behaviour problems (Fig. 3D) and anxiety symptoms. Conclusion: Young people with ASD have difficulties in executive functioning, however, neither behavioural nor neural measures of executive functioning were associated with co-occurring emotional and behavioural problems. Certain cognitive domains may be important to consider (e.g., perceptual processing atypicalities) when developing aetiological models of emotional and behavioural problems in young people with ASD. Funding: VCL was supported by an IoPPN/Medical Research Council Excellence Studentship. The QUEST study is part of the IAMHealth programme, funded by the NIHR. The SNAP project was supported by the Medical Research Council, with financial support from the Department of Health via the BRC. 25

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Publications: 1.

Carter Leno V, Vitoratou S, Kent R, Charman T, Chandler S, Jones CRG, HappĂŠ F, Baird G, Pickles A & Simonoff E. (2018). Exploring the neurocognitive correlates of challenging behaviours in young people with autism spectrum disorder. Autism. (in press) Carter Leno V, Chandler S, White P, Pickles A, Baird G, Hobson C, Smith AB, Charman T, Rubia K & Simonoff E. (2017). Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD. European Child and Adolescent Psychiatry, 81(10):S135 Carter Leno V, Chandler S, White P, Yorke I, Pickles A, Charman T & Simonoff E. Alterations in electrophysiological indices of perceptual processing are associated with co-occurring emotional and behavioural problems in adolescents with ASD. Submitted to Molecular Autism â&#x20AC;&#x201C; under peer review.

Figure 3. Associations between variation in different domains of cognition and emotional and behavioural problems in young people with ASD.

(A) and (B) Associations between ADHD symptoms and cognitive rigidity as measured by the switching reaction time cost and response variability; (C) Association between cognitive domains and aspects of behavioural problems; (D) Association between behaviour problems and neural indices of perceptual sensitivity as measured by the mismatch negativity difference wave.

Neurodevelopmental Disorders

Development of the observation schedule for children with autism spectrum disorders (ASD)–anxiety and behaviour (OSCA-AB): A new measure of parent and child behaviour for use with children with ASD

Investigators: Dr Melanie Palmer1, Dr Juan Paris Perez1, Dr Joanne Tarver1, Thomas Cawthorne1, Margot Frayne1, Sophie Webb1, Prof Tony Charman2, Prof Stephen Scott1, Dr Vicky Slonims3, Prof Andrew Pickles4, Prof Dale Hay5 & Prof Emily Simonoff1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Psychology, IoPPN, KCL; 3 Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London; 4 Department of Biostatistics and Health Informatics, IoPPN, KCL; 5 School of Psychology, Cardiff University.

Lay Summary: Our previous research showed that most 4-8-year olds diagnosed with an Autism Spectrum Disorder (ASD) display concerning emotions and behaviours. These included hyperactivity and inattention, oppositional behaviour and fears and worries. A challenge for the field of child and adolescent mental health is reliable and valid measurement of such emotions and behaviours. This is particularly important when we conduct evaluations of parent-focused intervention, where typically parents rate child behaviour and mental health as well as their own parenting behaviour before and after intervention. However, parental reports are likely to be influenced by a range of factors, so objective measures are needed. This study aims to develop a new observational measure of child and parent interactions for use with children with ASD. A range of researcher-led and parent-led tasks are completed. Tasks aim to simulate everyday challenges that children with ASD may face and find difficult. Initial findings suggest that a range of child and parent behaviours can be reliably measured. Children’s behaviours observed during the assessment appear to have some similarity with parental reports, however, parental reports of their own parenting practices were not similar to parent’s observed behaviours. As this work in ongoing, further refinement of the measure is required. State of Progress: Ongoing Abstract: Background: Most young children diagnosed with Autism Spectrum Disorders (ASD) display concerning and potentially problematic behaviours and emotions. Emerging evidence suggests that parent training interventions may reduce these difficulties in young children with ASD (Postorino et al., 2017). Trials of parent training frequently use parent-report measures as their primary outcome; however, as parents are the recipients of the intervention they are not blind to treatment status, which may lead to bias is estimating treatment effects (Sonuga-Barke et al., 2013). Objective measurement of these behaviours is therefore needed. Methods: The Observation Schedule for Children with Autism Spectrum Disorders – Anxiety and Behaviour (OSCA-AB) is a measure of child and parent interactions for use with children with ASD. It draws on existing well-validated observational measures of parent-child interaction. A range of researcherled and parent-led tasks are completed. Tasks were modified to simulate everyday challenges that children with ASD may face and find difficult. They aim to elicit concerning behaviours and emotions

CAMHS CAG Projects Day 2018

by tapping into uncertainty and novelty, transition, turn taking, sensory processing and compliance. Observed frequencies of parent behaviours (positive and negative comments, clear commands, physical handling, scaffolding) and child behaviours (compliance non-compliance, destructive behaviour, aggression to self and others, avoidance, proximity seeking) are coded. In addition, global codes are scored on a Likert scale. Intraclass correlation coefficients (ICCs) were used to establish inter-rater reliability (IRR) using a two-way mixed effects model. A more modest ICC of >.60 was considered adequate given that the measure is in development. Pearson correlation coefficients were calculated to investigate the associations between OSCA-AB scores and parent-reports of parent (Parenting Scale PS) and child behaviour (Aberrant Behaviour Checklist - ABC, Home Situations Questionnaire-ASD - HSQ-ASD). Results: Preliminary results from a sample of 18 families demonstrated that the OSCA-AB has promising psychometrics properties. Adequate IRR for scores on most child variables (ICCs >.60 for 10/15, Mdn=.69) and some parent variables (ICCs >.60 for 4/10, Mdn=.57) were reported. High correlations between the OSCA-AB scores and other validated measures of child behaviour are also evident (r=.64 and .61 for the ABC-Hyperactivity subscale and the HSQ-ASD, respectively). However, correlations between observed parent behaviours and parent-reports of their own parenting on the PS are low (r=.01-.07). Data collection is ongoing and the reliability and validity of the OSCA-AB will be tested among a larger sample. Conclusion: Preliminary results indicate that the OSCA-AB may be a useful objective measure for eliciting concerning behaviour and emotions and parent-child interactions in ASD. Refinement is required to increase IRR for some child and parent variables. Further research is needed to establish whether the OSCA-AB will be a valid measure of parent and child interactions among samples of young children with ASD and is sensitive to change following intervention. Funding: National Institute of Health Research (UK). Publications: Pending

Why do people with autism spectrum disorders fare so differently in adult life?

Investigators: Prof Emily Simonoff1, Prof Tony Charman2, Prof Gillian Baird3, Prof Andrew Pickles4, Prof Declan Murphy5, 6, Prof Martin Knapp7 & Prof Catherine Lord8 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Psychology, IoPPN, KCL; 3 Guy’s and St Thomas’ NHS Foundation Trust, King’s Health Partners; 4 Department of Biostatistics and Health Informatics, IoPPN, KCL; 5 Sackler Institute for Translational Neurodevelopment, IoPPN, KCL; 6 Department of Forensic and Neurodevelopmental Sciences, IoPPN, KCL; 7 Department of Social Policy, London School of Economics and Political Science; 8 Weill Cornell Medical College, Cornell University, New York, USA.

Lay Summary: There is widespread concern about outcomes for people with autism spectrum disorder (ASD) in adulthood and uncertainty about the personal and wider environmental factors that predict good 28

Neurodevelopmental Disorders

versus poor functioning. To address this, we studied a well-characterised, longitudinal and populationrepresentative sample of young adults with ASD from a unique cohort, the Special Needs and Autism Project (SNAP). SNAP participants were identified from the general population and initially assessed at age 12 years as part of a prevalence study of autism. The cohort has since been followed up at ages 16 and 23 years, with the most recent wave of data collection focusing on understanding the factors in childhood and adolescence that contribute to mental health and adaptive function in early adult life. Initial findings have focused on delineating the trajectories of intellectual functioning and adaptive function. Higher IQ level at all time points was predicted by baseline lower autism severity), lower language ability at 12 years and attending a mainstream (rather than change school. Within the cohort, a relative increase in IQ occurred in those who had experienced early childhood regression. Greater autism severity level at all time points was predicted by parental reports of early autism symptoms and greater emotional and behavioural problems. Relative increase in autism severity was predicted by attendance at a special school. State of Progress: Data collection is complete, analyses are ongoing Abstract: Background: Past studies of young people with ASD reveal poor outcomes. However, these findings are based on samples that were ascertained at a time when prevalence rates for ASD were much lower than those currently reported, which have converged at around 1% in both children and adults. Although the full reasons for the increasing prevalence are not established, it is generally agreed that the diagnostic conceptualisation has broadened to include a wider range of social communicative impairments and thereby also to identify a greater proportion of individuals with IQs in the normal range. The impact of the expanded definition on adult outcomes is unclear. The SNAP cohort is population-representative and comprises a diverse group of young adults, who were originally ascertained for a prevalence study and drawn from a total population of 56,946 children born July 1990-December 1991 inclusive and living in 12 health districts in South-east England (Baird et al. 2006). Some had previously received a clinical diagnosis while the majority (58%) had not received an ASD diagnosis by age 12 years. Findings from this study represent l young adults with ASD in the UK, whether or not they have been identified and received a clinical diagnosis, and can thus elucidate the impact of the broadened definition of ASD on adult outcomes. We will answer the following questions: (1) what is the range of outcomes for young adults with ASD?; (2) what are the factors, especially from childhood and adolescence, that predict good versus poor outcome?; (3) what are the drivers of the high economic costs of ASD in adulthood, and how far can they be predicted from childhood?; and finally, (4) can we reliably use cognitive markers for associated psychiatric problems that may help in earlier diagnosis and treatment of these additional problems? Methods: We aimed to follow-up the 158 young people with who comprised the longitudinal populationrepresentative cohort: (1) wave 1 at the age of 12 years (2) wave 2 at age of 16 years, limited to those with IQ â&#x2030;Ľ 50 and (3) current wave 3 at the ages of 23 years. The cohort underwent assessment of: (1) current ASD severity, on the Social Responsiveness Questionnaire; (2) intellectual ability on the Wechsler Abbreviated Scale of Intelligence; (3) adaptive function, on the Adaptive Behavior Assessment System (ABAS); (4) psychiatric symptoms and disorders, using a range of questionnaires and the Young Adult Psychiatric Assessment; (5) quality of life, (6) service use and economic costs; (7) a range of risk factor and protective factors, which include physical illnesses and problems and stressful life events such as being bullied and parental mental health, parental relationships, family stress and coping. A subpopulation also took part in a neurocognitive and neuroimaging study assessing attention-deficit/hyperactivity disorder (ADHD) symptom in young adult with ASD, which was found to be overrepresented among ASD children in the first wave of SNAP. 29

CAMHS CAG Projects Day 2018

Results: From 158 original participants, two participants had died, nine were untraceable and 21 declined to take part. Data were collected from 126 families, Parent/caregiver report only was collected for 16 participants and four young adults were seen without collecting a parent/caregiver report. Thirty young adults took part in the neurocognitive and neuroimaging study. From the present data, three papers are currently in preparation. In the first instance, latent growth curve models were undertaken to examine what childhood characteristics predict the developmental trajectories from childhood to early adult life if IQ and autism severity. These models evaluate the role of baseline variables from the first wave at age 12 on intercept – mean level over time - and slope – change in trajectory. Univariate models tested individual factors and formed the basis for final multivariate models. Higher IQ level at all time points was predicted by baseline lower autism severity), lower language ability at 12 years and attending a mainstream (rather than change school. Within the cohort, a relative increase in IQ with age occurred in those who had experienced early childhood regression. Greater autism severity level at all time points was predicted by parental reports of early autism symptoms and greater emotional and behavioural problems. Relative increase with age in autism severity was predicted by attendance at a special school. A propensity analysis confirmed this latter finding was not explained by other child or parental characteristics, which requires further exploration in other samples. Funding: Autism Speaks Publications: Scientific findings from SNAP have been summarised in over 30 peer-reviewed papers to date. In addition to the three reports currently prepared on the adult outcome of the cohort, researches are still undertaken using data collected in the previous waves of the study. Recent investigations have resulted in the below publications. 1.

Jones CRG, Simonoff E, Baird G, Pickles A, Marsden AJS, Tregay J, Happé F & Charman T. (2018). The association between theory of mind, executive function, and the symptoms of autism spectrum disorder. Autism Research. 11(1):95-109. 2. Lukito S, Jones CRG, Pickles A, Baird G, Happé F, Charman T & Simonoff E. (2017). Specificity of executive function and theory of mind performance in relation to attentiondeficit/hyperactivity symptoms in autism spectrum disorders. Molecular Autism. 8:60. 3. Milosavljevic B, Carter Leno V, Simonoff E, Baird G, Pickles A, Jones CRG, Erskine C, Charman T, Happé F. (2015). Alexithymia in adolescents with autism spectrum disorder: Its relationship to internalising difficulties, sensory modulation and social cognition. British Journal of Psychiatry. 207(5):392-9. 4. Carter Leno VC, Charman T, Pickles A, Jones CR, Baird G, Happé F & Simonoff, E. (2015). Callous–unemotional traits in adolescents with autism spectrum disorder. British Journal of Psychiatry, 207(5):392-399. 5. Barrett B, Mosweu I, Jones CRG, Charman T, Baird G, Simonoff E, Pickles A, Happé F & Byford S. (2015). Comparing service use and costs among adolescents with autism spectrum disorders, special needs and typical development. Autism. 19(5):562-9. 6. Hollocks MJ, Jones CR, Pickles A, Baird G, Happé F, Charman T & Simonoff E. (2014). The association between social cognition and executive functioning and symptoms of anxiety and depression in adolescents with autism spectrum disorders. Autism Research. 7(2):216-28. 7. Simonoff E, Jones CR, Baird G, Pickles A, Happé F & Charman T. (2013). The persistence and stability of psychiatric problems in adolescents with autism spectrum disorders. Journal of Child Psychology and Psychiatry. 54(2):186-94.

Neurodevelopmental Disorders

Also see the following summaries for related projects:

The cognitive and MRI correlates of attention-deficit/hyperactivity disorder symptoms in young adults with autism spectrum disorder (page 31) Specificity of executive function and theory of mind performance in relation to attentiondeficit/hyperactivity symptoms in autism spectrum disorders (page 34)

• •

The cognitive and MRI correlates of attention-deficit/ hyperactivity disorder symptoms in young adults with autism spectrum disorder

Investigators: Dr Steve Lukito, Prof Katya Rubia & Prof Emily Simonoff Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: People with autism spectrum disorder (ASD) often have symptoms of attention-deficit/hyperactivity disorder (ADHD) and it is unclear whether the ADHD symptoms found in ASD is similar or different from those found in people with “pure” ADHD. In a series of cognitive and functional magnetic resonance imaging (fMRI) studies, we compare the cognitive and neurofunctional impairments in young adults (aged 20-27 years and IQ ≥ 70) with typical development against those with pure ASD, ADHD and their combined presentation, i.e. ASD+ADHD. Our objectives were to find disorderspecific and shared neural impairments across these groups to enable us to form a model of impairments in the ASD+ADHD condition relative to the pure groups. This study is conducted as a part of a longitudinal study on an epidemiological cohort (Special Needs and Autism Project or SNAP) that has been followed since the age of 12-13 years and now young adults; in addition, participants are being recruited from clinical and volunteer samples to ensure adequate matching on key variables. State of Progress: Data collection is completed, analyses are ongoing Abstract: Background: Both ASD and ADHD are childhood-onset disorders that have lifelong consequences. Recent data suggest that attention deficit and hyperactivity symptoms are over-represented in ASD but the reasons for this are unclear. The current study aims to investigate the similarities or differences between such symptoms in the ASD and ADHD populations through structural and functional MRI and cognitive tasks. Methods: We compared 107 participants (aged 20-27 years and IQ ≥ 70) with pure ASD, ADHD, ASD+ADHD against typically developing (TD) controls, in a series of neurocognitive tasks assessing executive function (EF), including motor inhibition, sustained attention, visuospatial working memory, cognitive flexibility and temporal discounting; and social cognition (SC), including theory of mind and emotional face processing. The individuals also underwent structural and functional MRI scans while completing (1) a modified stop-signal task, which assesses the neural processing associated with motor inhibition and selective attention; (2) a time discrimination task, which assesses temporal processing; (3) the Frith-Happé animated triangle task, which assesses the neural processing during to mentalising; and (4) the dot-probe task, which assesses attentional bias towards emotional faces. Each individual also underwent a resting-state fMRI scan. 31

CAMHS CAG Projects Day 2018

Results and Conclusion: Different aspects of this study are in a various stage of completion. We have analysed data collected from the neurocognitive tasks, and the brain data during the modified stop-signal task, the time discrimination task and the Frith-HappĂŠ animated triangle tasks. (1) Neurocognitive studies During the EF tasks, univariate ANOVAs revealed that relative to TD, the ASD, ASD+ADHD and ADHD groups were impaired on primary measures of response inhibition (commission errors), sustained attention (omission errors) and working memory but the impairments in the ASD group did not survive covarying for IQ. The impairments in temporal discounting were specific to ADHD and remained when IQ was covaried. Cognitive flexibility did not differ across groups. During the SC tasks, the ASD and ASD+ADHD groups committed more errors during both SC tasks than the ADHD and TD groups, but only the FER errors in the ASD group remained after IQ was covaried. These demonstrated the associations between EF deficits and ADHD, SC deficits and ASD symptoms and the role of IQ as an explanatory factor for the variation of cognitive findings in adults in the populations. (2) The modified stop-signal fMRI task Preliminary results of the exploratory whole-brain analyses revealed an effect of group during unsuccessful inhibition in left insula/inferior frontal gyrus (IFG)/superior temporal/middle temporal gyri and right insula/IFG/thalamus/parahippocampal gyrus. Post-hoc t-tests showed that the ASD+ADHD group was under-activated in both clusters compared to the ASD, ADHD and TD groups, while the ASD, ADHD and TD groups did not differ from one another. Stop-signal response time (SSRT) was correlated with BOLD activation during unsuccessful inhibition in the TD and ASD+ADHD groups. Furthermore, group effect was also found on during selective attention in a cluster in right precuneus. Post-hoc t-tests showed that the ASD and ASD+ADHD groups had over-activation relative to the TD and ADHD groups. Missed responses were correlated with BOLD activation during selective attention in the TD group only. The neural correlates of successful inhibition did not differ across groups. All results remained after covarying for IQ. Therefore, during unsuccessful inhibition, young adults with comorbid ASD+ADHD demonstrated impairments in key regions of motor response inhibition typically found in boys with ADHD, which could be neurofunctionally associated with error monitoring or late-arriving motor inhibition activation. The over-activation found in right precuneus in the ASD and the ASD+ADHD groups could signify reduced de-activation of the default mode network (DMN). In summary, the neural impairments in the motor inhibition regions were specific to the ASD+ADHD group, while impairments in the DMN region was associated with ASD diagnoses in adulthood. (3) The time discrimination fMRI task Hypothesis driven region-of-interest analyses showed an effect of group during duration discrimination in a cluster in right IFG region, with post-hoc comparisons showing that the ASD+ADHD group had less activation than the other groups. Co-varying for IQ reduced the group effect to a trend level, preserving the pairwise difference between the ASD+ADHD and the TD or ASD, but not the ADHD group. Group effect was maintained after excluding participants on medication, with post-hoc tests showing reduced activation in the ASD+ADHD group relative to the TD and ASD, but not the ADHD group and no other significant pairwise differences were found. The right IFG activation cluster negatively correlated with SDRT in the TD group but not in the clinical groups. Exploratory whole-brain analyses revealed an under-activated cluster in right IFG/DLPFC in the ASD+ADHD relative to the TD group that did not survive after covarying for IQ or after excluding those prescribed medication. The findings suggested that only the ASD+ADHD group showed reduced activation in right IFG during duration discrimination relative to TD controls and the pure ASD and ADHD groups, who were unimpaired. However, the findings must be viewed in light of the possible moderating influence of IQ and medication use among individuals in the population studied.

Neurodevelopmental Disorders

(4) The Frith-Happé animated triangle fMRI task Exploratory whole-brain analyses revealed a group effect on the activation in right angular gyrus. IQ was not a significant covariate in the model and was not included in the subsequent analyses. Posthoc pairwise comparisons, corrected with Tukey-Kramer method, showed that activation in right ANG cluster was increased in the ASD and ASD+ADHD compared to the ADHD group, although none of the groups differed relative to TD controls. Additional Group effects were found in the ROI analyses in right SFG and left IFG. The effect of IQ was again non-significant in the betweengroup models of activation clusters, so IQ was removed from the model. Post-hoc pairwise comparisons showed significantly lower activation in right SFG in the ADHD than the ASD+ADHD group and, at trend-level, the TD controls. The left IFG activation was similarly lower in the ADHD than the ASD+ADHD and, at trend level, the ASD group. No other pairwise differences were significant. Activation in left IFG cluster negatively correlated with self-rated ADHD symptoms in the ADHD group. No other correlations between cluster activation and symptoms were significant. To summarise, the ASD and ASD+ADHD group shared similar patterns of over-activation in right angular gyrus. Furthermore, reduced activation in left IFG in the ADHD relative to the ASD+ADHD group was associated with increased ADHD symptoms. Overall these findings suggest that mentalising in ADHD could be underpinned by both ADHD- and ASD-specific neural impairments. Funding: SL was supported by the UK Medical Research Council (MRC) and IoPPN PhD Excellence awards. DI was supported by the Alicia Koplowitz Foundation Fellowship in Child and Adolescent Psychiatry and Psychology. ES and KR are supported by the by the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and the Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King’s College London. Publications: 1.

Ilzarbe D, Lukito S, Moessnang C, O’Daly O, Lythgoe DJ, Murphy C, Ashwood K, Stoencheva V, Rubia K & Simonoff E. Neural correlates of theory of mind in autism spectrum disorder, attention-deficit/hyperactivity disorder, and the comorbid condition. Submitted to Psychological Medicine 2. Lukito S, O’Daly O, Lythgoe DJ, Maltezos S, Pitts M, Simonoff E & Rubia K. (2018). Executive function and social cognition impairments in autism spectrum disorder, attention-deficit/hyperactivity disorder and comorbid presentation. Poster presented at International Society for Autism Research (INSAR) Annual Meeting: May 9-12; Rotterdam, Netherland. 3. Lukito S, O’Daly O, Lythgoe, DJ, Maltezos S, Pitts M, Simonoff E & Rubia K. (2018). Neural Correlates of unsuccessful inhibition and selective attention in young adults with ASD, ADHD and comorbid presentation during the modified stop-signal task. Poster presented at International Society for Autism Research (INSAR) Annual Meeting: May 9-12; Rotterdam, Netherland. 4. Lukito S, O’Daly O, Lythgoe DJ, Whitwell S, Short A, Simonoff E & Rubia K. (2017). The neurofunctional correlates of time discrimination in young adults with autism spectrum disorder, attention-deficit/hyperactivity disorder and the comorbid condition. Poster presented at the summer meeting of the British Association of Psychopharmacology, July 23-26; Harrogate Manuscripts are in preparation.

CAMHS CAG Projects Day 2018

Specificity of executive function and theory of mind performance in relation to attention-deficit/ hyperactivity symptoms in autism spectrum disorders

Investigators: Dr Steve Lukito1, Dr Catherine R. G. Jones2, Prof Andrew Pickles3, Prof Gillian Baird4, Prof Francesca Happé5, Prof Tony Charman6 & Prof Emily Simonoff1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 School of Psychology, Cardiff University; 3 Department of Biostatistics and Health Informatics, IoPPN, KCL; 4 Guy’s and St Thomas’ NHS Foundation Trust, King’s Health Partners, 5 Social, Genetic and Developmental Psychiatry (SGDP) Centre, IoPPN, KCL; 6 Department of Psychology, IoPPN, KCL.

Lay Summary: Approximately 30-60% of children with autism spectrum disorder (ASD) meet the criteria for attention-deficit/hyperactivity disorder (ADHD). It is unclear how these symptoms are related to the cognitive domains such as theory of mind (ToM), i.e. the ability to understand the mental states in others, and executive function (EF), such as the capacities for working memory, planning and inhibiting actions, that are typically impaired in people with ASD. We used statistical modelling approach to explore the relations among EF, ToM, and symptoms of ASD and ADHD, using data from a population-based sample of 100 adolescents with ASD and full-scale IQ ≥ 50. Multiple measures from different informants were used, including from parents, teacher, and from the young person themselves. The effect of shared reporting from parents and the effect of IQ variations in the model were also investigated. Our findings showed that in this population-based sample of adolescents with ASD, symptoms of ADHD and ASD are underpinned by separate cognitive domains. The ADHD symptoms are associated specifically with EF impairments, while ASD symptoms are associated with ToM impairments. There is a correlation between EF and ToM impairments, which could be an explanation for the co-occurrence of ADHD symptoms in ASD. The severity of ASD symptoms is also associated with ADHD symptoms in these children, which is partially explained by the shared reporting effects by parents. This underlines the importance of having multiple sources of independent informants of in future research. This model remained when IQ variation in the participants was taken into account. State of Progress: Completed Abstract: Background: Individuals with autism spectrum disorder (ASD) frequently demonstrate symptoms of attentiondeficit/hyperactivity disorder (ADHD). Previous findings in children with ASD have suggested that these symptoms are associated with an impairment in executive function (EF) abilities. However, studies rarely considered this association within a single framework that controls for other related factors such as theory of mind (ToM) abilities and ASD symptoms. Methods: We used structural equation modelling to explore the relations among EF, ToM, and symptoms of ASD and ADHD, using data from a population-based sample of 100 adolescents with ASD and fullscale IQ ≥ 50 (the Special Needs and Autism Project [SNAP] cohort). The study used a multi-measure and multi-informant approach, where performance of inhibition, planning, switching, and working

Neurodevelopmental Disorders

memory tasks indexed EF and performance on tasks involving mentalising indexed ToM. Measures of ASD and ADHD symptoms included parent and teacher reports and direct observation of the children. Shared source of symptom reporting was accounted for with a parental rating latent factor indexed by symptom measures reported by parents. Figure 4. Specific associations between EF and ADHD symptoms and ToM and ASD symptoms in adolescents with ASD.

The effects of shared source of reporting from parents are controlled in both Models 1 and 2. Controlling for IQ in Model 2 did not change the specific relations between factors. Abbreviations. EF = executive function, ToM = theory of mind, ASD = autism spectrum disorder, ADHD = attention-deficit/hyperactivity disorder. CST = card sort task, TMT= trail making task, OW = opposite world; NB = number backward, PD = planning drawing, AT = animated triangles, PHG = penny hiding game, RME = reading the mind in the eye. DSM = ADHD symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, SDQ = Strength and Difficulties Questionnaire, PONS = Profile of Neuropsychiatric Symptoms, ADOS = Autism Diagnostic Observation Schedule, ADI-R = Autism Diagnostic Interview-Revised, SRS = Social Responsiveness Scale, t = teacherrated, p = parent-rated. 35

CAMHS CAG Projects Day 2018

Results: Impairments in EF abilities were specifically associated with ADHD symptoms while impaired ToM was specifically associated with ASD symptoms, when accounting for the associations of each cognitive domain with the other factors. ASD and ADHD symptom latent factors were also correlated, but this association became nonsignificant once the shared source of reporting from parents was accounted for and within a model that also controlled for the correlated pathway between EF and ToM factors. The specific relations between the cognitive domains and behavioural symptoms remained even after controlling for IQ. Conclusion: In this ASD sample, symptoms of ADHD and ASD are underpinned by separate cognitive domains. The association between EF and ToM impairments is a likely partial explanation for the co-occurrence of ADHD symptoms in ASD, but the role of shared reporting effects is also important and supports the inclusion of independent informants and objective measures in future research. Funding: SL was funded by the Medical Research Council-IoPPN PhD Excellence Awards. The SNAP project was supported by the Medical Research Council, with financial support from the Department of Health via the BRC. Publication:

Lukito S, Jones CRG, Pickles A, Baird G, Happé F, Charman T & Simonoff E. (2017). Specificity of executive function and theory of mind performance in relation to attentiondeficit/hyperactivity symptoms in autism spectrum disorders. Molecular Autism. 8(60) doi: 10.1186/s13229-017-0177-1.

Detection of suicidality in adolescents with autism spectrum disorder: Developing a natural language processing approach for use in electronic health records

Investigators: Dr Johnny Downs, MRCPsych1,2, Dr Sumithra Velupillai, PhD2,4 Dr George Gkotsis, PhD2, Rachel Holden, MSc1,5, Maxim Kikoler, MSc1,5, Harry Dean, MSc2, Andrea Fernandes, MSc2,3 & Dr Rina Dutta, PhD, FRCPsych2,3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL). 2 NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; 3 Department of Psychological Medicine, IoPPN, KCL. 4 School of Computer Science and Communication, KTH, Stockholm; 5 University of Canterbury, Southborough, UK.

Lay Summary: It is important that clinicians and researchers who study and work in Child and Adolescent Mental Health Services (CAMHS) can understand how common certain mental health problems are in young people who access mental health services. One important area is suicidality, which is a term used to capture thoughts, plans or attempts that a young person may have to end their life. Current methods of checking how the numbers or patterns of young people who clinicians report as being suicidal in their health record are problematic. Much of this information is not easily detected using standard software, as it is written in text using the clinician’s own language rather than using checkboxes or drop down menus. Also, many clinicians will report that a young person “is not suicidal” or use other terms which show they think the young person is not showing any worrying signs of feeling suicidal. We developed

Neurodevelopmental Disorders

a way of searching through millions of electronic health care records using sophisticated computer methods called Natural Language Processing (NLP). We then applied this approach to study the patterns of suicidality in young people with autism spectrum disorder (ASD) – as very little research has been conducted in this area, and many families and clinicians are saying that it is a real issue within CAMHS. We found that we could determine with nearly 90% accuracy, which young people with ASD had described feeling suicidal. We now hope to use this NLP technique to examine what characteristics of the young person and their situations lead to feeling suicidal, and how we can prevent these feelings leading onto a suicide attempt. State of Progress: Future Abstract: Background: Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet, there is limited evidence concerning risk factors for suicidality in childhood ASD. Electronic health records (EHRs) can be used to create retrospective clinical cohort data for large samples of children with ASD. However, systems to accurately extract suicidality-related concepts need to be developed so that putative models of suicide risk in ASD can be explored. Methods: We present a systematic approach to (1) adapt Natural Language Processing (NLP) solutions to screen with high sensitivity for reference to suicidal constructs in a large clinical ASD EHR corpus (230,465 documents, 1706 young people with ASD), and (2) evaluate within a screened subset of 500 young people, the performance of an NLP classification tool for positive and negated suicidal mentions within clinical text. Results: Approximately 20% of the sample had suicidal thoughts or behaviours. When evaluated, the NLP classification tool showed high system performance for positive suicidality with precision, recall, and F1 scores all > 0.85 at a document and patient level. Conclusion: The application therefore provides accurate output for epidemiological research into the factors contributing to the onset and recurrence of suicidality, and potential utility within clinical settings as an automated surveillance or risk prediction tool for specialist ASD services. Funding: JD is supported by a Medical Research Council (MRC) and Psychiatry Research Trust Peggy Pollak Fellowship. SV is supported by the Swedish Research Council (2015-00359), Marie Skłodowska Curie Actions, Cofund, Project INCA 600398, HD received salary support from the Foundation of Professional Services to Adolescents, RD is funded by a Clinician Scientist Fellowship (research project e-HOST-IT) from the Health Foundation in partnership with the Academy of Medical Sciences. All investigators are supported by National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Publication:

Downs J, Velupillai S, Gkotsis G, Holden R, Kikoler M, Dean H, Fernandes A, Dutta R.(2018). Detection of suicidality in adolescents with ASD: Developing a natural language processing approach for use in electronic health records. Proceedings of the American Medical Informatics Association (in press) https://amia2017.zerista.com/event/member/389361

CAMHS CAG Projects Day 2018

Predictors of death by suicide in autism spectrum disorder

Investigators: Dr Johnny Downs1, 2, Catherine Polling2,3, Dr Sumithra Velupillai2, Prof Emily Simonoff1,2, Dr Rina Dutta1, Dr Sophie Epstein1,2, Dr Tarek Mostafa5, Prof Ruth Gilbert6, Prof Matthew Hotopf2, Prof Tamsin Ford4 & Prof Richard Hayes1,2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 NIHR South London and Maudsley NHS Foundation Trust Biomedical Research Centre; 3 School of Computer Science and Communication, KTH, Stockholm; 4 University of Exeter Medical School; 5 UCL Centre for Longitudinal Studies, University College London; 6 Administrative Data Research Centre for England, UCL Great Ormond Street Institute of Child Health.

Lay Summary: Adults with ASD are 2-3 times more likely to die by suicide than adults without ASD. We need to know how to better pick-up mental health concerns in ASD to prevent these tragic outcomes. One approach is to see whether early problems that may lead to death by suicide could have been detected quicker. One of the strongest early predictors of death by suicide is severe self-harm in adolescence. Fortunately, severe self-harm is rare, but there are some studies that show that young people with ASD are at greater risk for suicidal thoughts and behaviours than typically developing children. No studies have been able to be sufficiently large enough to detect whether ASD children are at greater risk of self-harm. We used a very large education database which contained information on all children attending secondary school in four boroughs of south London linked with Child and Mental Health Services (CAMHS) electronic records to see who had presented to accident and emergency (A&E) with self-harm. We found girls were much more likely in general than boys to present with self-harm, however boys with ASD were nearly three time more likely to attend accident and emergency with self-harm than non-ASD boys. We found that for both boys and girls, being “in care”, having problems with school attendance, being excluded from school, and having attention-deficit/hyperactivity disorder (ADHD) predicted later self-harm. We found that nearly 50% who first came to A&E were not known to CAMHS. These findings provide an important first step in demonstrating that services who work with children with ASD and ADHD in schools and in CAMHS, have a role in early detection for self-harm. Services should also help children with ADHD and ASD not just find a better way to cope with difficulties that they are directly experiencing from their conditions, but also help them with strategies for handling difficulties as they grow older which may lead to them hurting themselves through self-harming. State of Progress: Ongoing Abstract: Background: Presentation to emergency care with injuries related to self-harm is one of the strongest predictive factors for later suicide attempt, with 26% of future suicide attempts attributed to self-harm in adolescence and young adulthood. Recent findings show individuals with autism spectrum disorders (ASD) have a 2-3-fold increase risk of premature mortality compared to the general population, with suicide as the leading cause. The risk of self-harm severe enough to warrant emergency treatment has yet to be robustly evaluated in ASD. This study assessed whether individuals with ASD are at increased risk of self-harming in adolescence. Methods: This was a population based retrospective cohort study. The source population were residents of four

Neurodevelopmental Disorders

South London boroughs, aged 11-17 years, attending secondary school identified from the NPD. Exposure data on ASD status were derived from the pupil database. Outcome (self-harm data) were derived by linking the education record with CAMHS records. Results: Among 113,543 adolescents attending secondary school, 186 boys (0.3%) and 834 (1.4%) girls presented to accident and emergency with self-harm over a 4-year follow-up period; less than 50% of whom were previously known to NHS mental health services. In the sample, 2463 adolescents were identified with ASD. For boys, there was a significantly increased risk of self-harm associated with ASD (aH.R 2.79, 95% confidence interval 1.47 to 5.09, p<.01) after adjustment for potential confounding factors, including baseline behavioural & emotional problems, academic attainment, persistent school absence, exclusion, socio-economic status, being in local authority care, and hyperkinetic disorder diagnosis. For girls, ASD was not associated with elevated risk, but a number of educational, social and clinical related factors were identified as significant predictors of self-harm, including persistent school absence (aH.R 2.84, C.I 2.70- 3.51, p<.01), and being in higher quintiles of academic attainment (aH.R 1.35, C.I 1.04-1.77, p=.03). Conclusions: This study provides robust evidence that ASD, and a number of other educational factors, are population level risk factor for self-harm. Risk is not equal across gender, with ASD associated with a greater susceptibility to self-harm only amongst boys. These finding are an important first step in developing early recognition and future prevention programmes within schools and other child orientated services. Funding: Medical Research Council Fellowship (JD), Psychiatry Research Trust Peggy Pollak Fellowship (J.D); ESRC Administrative Data Research Network (R.G, TM), NIHR Child Policy Research Unit (R.G) MQ Data Science award (S.V, R.D, J.D, S.E) the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London Figure 5. Self-harm incidence rates of adolescents presenting to Accident & Emergency according to age and gender

CAMHS CAG Projects Day 2018

Biomarkers of childhood-onset neurodevelopmental disorders (BioNeD)

Investigators: Prof Patrick Bolton1,2, Prof Philip Asherson2, Dr Karen Ashwood3, Dr Bahare Azadi1, Dr Charlotte Tye1,2, Dr Lizzie Shephard1,2& Dr Grainne McLoughlin2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL; 3 Forensic and Neurodevelopmental Sciences, IoPPN, KCL

Lay Summary: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are common childhood-onset neurodevelopmental disorders, which often co-occur in the same individual. A diagnosis of ASD with ADHD typically gives rise to serious lifelong disabilities that cause considerable distress to individuals and their families. Our understanding of the underlying cognitive and brain features that are shared or unique to ASD and ADHD is limited. In order to tease these apart, it is important to directly compare underlying cognitive and brain features across children with cooccurring ASD+ADHD and children with “pure” ASD and “pure” ADHD. In the BioNeD study, we used a combination of behavioural observations, cognitive tasks and objective eye-tracking and electroencephalography (EEG) tests, which measures naturally occurring signals occurring from brain activity. We recruited over 100 children aged 7-16 years with ASD, ADHD and co-occurring ASD+ADHD, who underwent comprehensive research diagnostic assessment, and were compared to 30 typically developing children. Our findings indicated that we could distinguish between children with ASD and ADHD on the basis of their brain responses, whereby children with ADHD showed problems in inhibiting their responses, whereas children with ASD showed abnormal brain responses to face stimuli. Importantly, children with co-occurring ASD+ADHD appear to display the unique cognitive and brain features of ASD and ADHD. By measuring cognitive and brain development across disorders we are able to identify unique and shared mechanisms. This can help us to target more specific and tailored treatments and interventions to more complex cases. State of Progress: Data collection completed, analysis ongoing Abstract: Background: There is significant clinical, behavioural and genetic overlap between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), two common childhood-onset disorders. Extensive work aimed at identifying the underlying mechanisms involved in the overlap has revealed complex clinical and aetiological heterogeneity. In order to determine whether the comorbid condition differs from the simple additive combination of the deficits associated with ASD and ADHD when they occur alone, it is necessary to stratify groups and compare underlying cognitive and brain correlates in the comorbid group to ‘pure’ disorders. Methods: In the BioNeD study, we administered an extensive test battery to over 100 comprehensively assessed children aged 7-16 years with ASD, ADHD and comorbid ASD+ADHD and 30 typically developing children. Our battery included measures of executive function, social cognition, eye-tracking and event-related potentials (ERPs), as well as information on pre and peri-natal factors and genetics. Results: Several findings from the BioNeD project have now been published. Assessment of adaptive

Neurodevelopmental Disorders

functioning indicated exacerbated impairments in children with ASD+ADHD relative to children with ADHD, associated with ASD symptoms. Children with ASD and ADHD differed in event-related potentials (ERPs) recorded from the EEG; for example, children with ADHD showed attenuated responses during an attentional cued-continuous performance test, whereas abnormal ERP responses were observed during a face processing task in children with ASD. Across cognitive tasks and EEG tests, children with ASD+ADHD displayed the unique deficits of ASD and ADHD. Conclusion: Our findings to date converge to suggest that children with ASD and ADHD can be dissociated while children with ASD+ADHD present as an additive co-occurrence with the unique deficits of both ASD and ADHD. The ultimate goal of this work is to elucidate gene-brain-behaviour pathways to neurodevelopmental disorders in order to design and target more specific treatment strategies. Funding: NIHR Maudsley BRC, Medical Research Council, Waterloo Foundation, Steel Charitable Trust Publications: 1.

Shephard E*, Tye C*, Asherson P, Ashwood KL, Azadi B, Bolton P & McLoughlin G. (2018). Resting-state neurophysiological activity patterns in young people with ASD, ADHD and ASD+ADHD. Journal of Autism and Developmental Disorders, 48(1): 110-122. 2. Tye C*, Bedford R*, Asherson P, Ashwood KL, Azadi B, Bolton P & McLoughlin G. (2017). Callous-unemotional traits modulate neurophysiological profiles in children with autism spectrum disorder and attention deficit hyperactivity disorder. Developmental Cognitive Neuroscience, 26: 84-90. 3. Tye C, Johnson KA, Kelly S, Asherson P, Ashwood K, Azadi B, Kuntsi J, Bolton P & McLoughlin G. (2016). Response time variability under slow and fast-incentive conditions in ASD, ADHD and ASD+ADHD. Journal of Child Psychology and Psychiatry, 57(12): 14141423. 4. De Jong S, Newhouse SJ, Patel H…Asherson P…Tye C., Ashwood KL, Bolton P…Breen G. (2016). Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis. British Journal of Psychiatry, 209 (3): 202-208. 5. Ashwood KL*, Tye C*, Azadi B, Asherson P & Bolton P. (2015). Brief report: Adaptive functioning in children with ASD, ADHD and ASD+ADHD. Journal of Autism and Developmental Disorders, 45(7): 2235-2242. 6. Tye C, Battaglia M, Bertoletti, E, Ashwood K, Azadi B, Asherson P, Bolton P & McLoughlin G. (2014). Altered neurophysiological responses to emotional faces discriminate children with ASD, ADHD and ASD+ADHD. Biological Psychology, 103: 125134. 7. Tye C, Asherson P, Ashwood K, Azadi B, Bolton P & McLoughlin G. (2014). Attention and inhibition in children with ASD, ADHD and comorbid ASD+ADHD: an eventrelated potential study. Psychological Medicine, 44(5): 1101-1116. 8. Tye C, Mercure E, Asherson P, Ashwood K, Azadi B, Johnson, MH, Bolton P & McLoughlin G. (2013). Neurophysiological responses to faces and eye gaze differentiate children with ASD, ADHD and ASD+ADHD. Developmental Cognitive Neuroscience, 5: 7185.

*joint first author

CAMHS CAG Projects Day 2018

Development of the tailored Rett intervention and assessment longitudinal (TRIAL) database and the Rett evaluation of symptoms and treatments (REST) questionnaire

Investigators: Dr Jatinder Singh1, Rachel Smith1, Dr Kate Lievesley1,3, Dr Federico Fiori1,2,3 & Prof Paramala Santosh1,2,3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust; 3 HealthTracker Ltd, Gillingham, Kent.

Lay Summary: Rett Syndrome (RTT), a pervasive neurological is characterised by compromised brain functions, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. It is predominantly found in young females with an incidence of 1:10,000â&#x20AC;&#x201C;20,000 live births. RTT is associated with poor long-term outcomes and as far as we are aware, no complete all-embracing instrument has been developed for patients with RTT that has the ability to capture longitudinal pharmacological, behavioural and genetic information, and be able to correlate this with the physiological aspects of the disease. The aim of this study was to develop a multi-dimensional questionnaire to measure patient centred symptoms (including somatic and behavioural), cognition and physiology for use in assessing treatments for RTT. State of Progress: Ongoing Abstract: Background: This study will develop a single, all-encompassing questionnaire for RTT. A single multidimensional and reliable questionnaire is needed especially one that can embrace all symptoms, and the relationships between them, and one that can also map clinically meaningful data to symptomatology across the lifespan in patients. This questionnaire is called the Rett Evaluation of Symptoms and Treatments (REST) questionnaire and will be used to profile the symptomatology of patients with RTT across the lifespan allowing better understanding of patient needs. Methods: The development of the REST questionnaire followed the FDA framework for Patient Reported Outcome Measures. Information captured using the REST questionnaire will be linked to outputs using wearable sensor technology and genetic data and information about available psychosocial support from the patient and their family, to form a comprehensive Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database. It is anticipated that the TRIAL database will enable the streamlining of treatment and expedite triaging of care by signposting patients to correct specialists sooner to enable timely intervention and the use of HealthTrackerTM, a multi-modal eHealth webbased monitoring platform, will make the TRIAL database as user friendly as possible. Results/Conclusion: This study is on-going and data collection has been commenced. Funding: This research was funded by Reverse Rett UK (Ref No: PCCTABR)

Neurodevelopmental Disorders

Publication:

Santosh P, Lievesley K, Fiori F & Singh J. (2017). Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) questionnaire. BMJ Open. 7(6):e015342.

Conflict of Interest: P. Santosh is director & CEO and stockholder in HealthTracker Ltd. F. Fiori is a Data Analyst employed by HealthTracker Ltd. K. Lievesley is a Project Manager employed at HealthTracker Ltd.

Sarizotan treatment of apneas in Rett syndrome (STARS)

Investigators: Dr Samiya Chishti1, Asimina Tsirka1, Mathilde Mastroianni1, Dr Jatinder Singh1, Dr Federico Fiori1,2, Dr Maria Xirou2, Dr Remus Florea2, Noah Yogo3, Elka Giemza3, Glynis Ivin4, Dr Ravi Anand5 & Prof Paramala Santosh1,2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust; 3 Clinical Research Facility, Kingâ&#x20AC;&#x2122;s College Hospital, London; 4 Pharmacy Department, South London and Maudsley NHS Foundation Trust; 5 Newron Pharmaceuticals SpA, Bresso (MI), Italy.

Lay Summary: Sarizotan Treatment of Apneas in Rett Syndrome (STARS) is a randomised, double blind, placebocontrolled multi-centre clinical trial to evaluate the efficacy, safety and tolerability of Sarizotan in patients with Rett syndrome suffering from respiratory symptoms. State of Progress: Ongoing Abstract: Background: Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with impairments in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Divergent mutations in the gene implicated in RTT-methyl-CpG-binding protein 2 (MeCP2) establishes RTT as a disorder with broad symptomatology ranging from individuals with severe to milder phenotypes. Respiratory dysfunction is a serious concern in patients with RTT and episodes of apnoea, hyperventilation and disordered breathing can significantly affect the quality of life. The aim of STARS is to explore the serotonergic 5HT1A receptor system in patients with RTT with a view to improve their breathing dysfunction. Methods: This clinical trial is a double blind, placebo-controlled randomised study in patients with RTT syndrome. Results: The primary endpoint for the STARS study is reduction in episodes of clinically significant apneas (>10 sec) during waking time by 20 percent. During this study, patients will receive treatment with daily doses of 10 and 20 mg of Sarizotan, or placebo.

CAMHS CAG Projects Day 2018

Conclusion: Sarizotan received Orphan Drug Designation for the treatment of Rett syndrome from both the European Commission and the FDA in 2015. If the study proves successful, this could become the first therapy approved for the treatment of Rett syndrome patients. Funding: Newron Pharmaceuticals Publications: Pending

Systematic phenotyping in neuroimaging (SPIN) study

Investigators: Ilyas Sagar-Ouriaghli1, Dr Nantia Iakovidou1, Dr Federico Fiori2, Dr Jatinder Singh2, Prof Mitul Mehta3, Prof Steven Williams3 & Prof Paramala Santosh1, 2,4 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD) Research Team, South London and Maudsley NHS Foundation Trust; 3 Department of Neuroimaging, IoPPN, KCL; 4 HealthTracker Ltd, Gillingham, Kent.

Lay Summary: Currently, there are many barriers to introducing neuroimaging findings into clinical care. In psychiatric research, neuroimaging methods are constantly evolving but are yet to develop a single biomarker enabling researchers to confidently tease apart healthy controls from those with varying psychiatric diagnoses. The Profile of Neuropsychiatric Symptoms (PONS) questionnaire can be used to measure clinically meaningful change longitudinally. The HealthTracker™ based PONS questionnaire can be implemented for neuroimaging purposes to phenotypically profile patients across disorders having new scans or for pre-existing patients who have had neuroimaging scans done in the last 12 months. The goal of this study is to develop a phenotype capture system for the HealthTracker™ platform using neuroimaging and neuropsychiatric data to assist in the diagnosis and treatment of children and adolescents with mental health diagnoses. State of Progress: Ongoing Abstract: Background: Neuroimaging research has the potential to enhance the quality of life of individuals, especially those with neuro-disabilities by providing more effective treatment strategies. Moreover, mental health providers seem to be highly receptive and in favour for the incorporation of neuroimaging data into clinical practice, not only to improve our understanding but also to enhance diagnosis and the level of care provided to each patient. Despite this, the full integration of biomarkers such as neuroimaging into current practice is yet to find traction. Many neuroimaging studies within psychiatry remain orientated towards research and there is a pressing need for the clinical integration of these new technologies. Methods: This study is an observational study that will consist of identifying and profiling study participants who are set to complete or have previously undergone a neuroimaging scan within the last 12 months. Identified study participants will complete the PONS questionnaire, which will be used to help provide a multi-dimensional measure of their neuropsychiatric symptoms. A demographic questionnaire will 44

Neurodevelopmental Disorders

also be used to capture demographic data. Both the neuroimaging data and the output of the PONS questionnaire will be analysed together to define a phenotype of the study participant based on realtime neuroimaging data. Results & Conclusions: Data collection and analysis is still ongoing, therefore no results have been published or conclusions reached. By using the HealthTrackerâ&#x201E;˘ web-based PONS questionnaire in conjunction with neuroimaging data across a range of psychiatric and neurodevelopmental disorders, the overarching aim of this project is to systematically identify specific phenotypes associated and be able to correlate this with specific brain structures. This will pave the way for the integration of neuroimaging data to assist in the diagnosis and treatment of children and adolescents with mental health diagnoses. Funding: This research was funded by the NIHR/BRC Neuroimaging Theme Translational/Impact Call: Project code TL004. Publications: Pending Conflict of Interest: P. Santosh is director & CEO and stockholder in HealthTracker Ltd. F. Fiori is a Data Analyst employed by HealthTracker Ltd. K. Lievesley is a Project Manager employed at HealthTracker Ltd.

Early development in tuberous sclerosis (EDiTS)

Investigators: Dr Charlotte Tye1,2, Prof Patrick Bolton1,2, Prof Mark Johnson3, Dr Emily Jones3 & Dr Luke Mason3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL; 3 Centre for Brain and Cognitive Development, School of Psychology, Birkbeck, University of London.

Lay Summary: Tuberous sclerosis complex (TSC) is a rare genetic disorder associated with varied behavioural and cognitive problems in later childhood, including problems in social communication (e.g. autism spectrum disorder), attention (e.g. attention deficit hyperactivity disorder) and cognitive ability (e.g. intellectual disability). Little is known about how development in TSC differs in the early years from typical development, and how the behavioural and cognitive problems are influenced by certain factors, such as epilepsy. This is because previous work has asked parents to try to recall what their child was like in the first two years, and also because the tests used were not sensitive enough to sudden changes in these factors. The suggestion that new treatments can be given to babies with TSC also highlights the need for a tailored procedure to systematically chart their development. In this study, we are aiming to design and test a new protocol in babies with TSC from 3 to 24 months of age, and compare their developmental trajectories to those of typically developing babies. Within the test battery, we include novel state-of-the-art eye-tracking tests that can be administered in the research laboratory and at home, in collaboration with the Centre for Brain and Cognitive Development at Birkbeck. These tests are able to tell us more about social and attentional problems in TSC, even before the baby is able to respond to experimental tasks or speak. The results from this study will help us to understand how babies with TSC develop, which factors are linked to behavioural outcome, and the effects of epilepsy and treatment very early in life. 45

CAMHS CAG Projects Day 2018

State of Progress: Ongoing Abstract: Background: Tuberous sclerosis complex (TSC) is a rare genetic disorder, characterised by the growth of benign lesions which grow throughout multiple organ systems. Epilepsy is present in 60-90% of individuals and around two-thirds of individuals with TSC and epilepsy have seizure onset in the first year of life. Children with TSC are at high risk of cognitive, behavioural and psychiatric disturbances; a large proportion will develop intellectual disability, and 30-60% of individuals with TSC meet criteria for autism spectrum disorder (ASD). Of studies that have explored factors associated with behavioural outcomes in TSC, the majority have been small-scale, uncontrolled, retrospective investigations of clinic populations after a psychiatric diagnosis has been made. The number of cases presenting with abnormalities at routine antenatal examination has increased and now accounts for a substantial minority of cases, providing a unique opportunity to study risk pathways from birth in this population, prior to emergence of behavioural symptoms. Methods: The Early Development in Tuberous Sclerosis (EDiTS) Study is an ongoing prospective longitudinal study of infants with TSC (total n=25) and age-matched typically developing infants (total n=25) enrolled from 3 to 24 months of age. Infants undergo developmental assessments (e.g. Mullen Scales of Early Learning) at each visit and complete a range of behavioural tasks. We use portable eye-tracking technology in the home environment to measure social and non-social attention. At certain age points, infants with TSC are invited to the Centre for Brain and Cognitive Development (CBCD), Birkbeck, to conduct a more extensive range of assessments including electroencephalography (EEG) and electrocardiography (ECG). Results: To date, we have recruited 23 infants with TSC and 30 typically developing infants, and conducted over 170 assessments. We have initiated a UK-wide clinical network of foetal medicine units, clinical geneticists and specialist TSC clinics to recruit infants with TSC. Preliminary data analysis with 10 infants with TSC and 15 typical infants (data collection ongoing) indicates a slower gain of developmental skills in infants with TSC, particularly for the non-verbal domain, from 5 to 10 months of age, associated with younger age at seizure onset. We have also analysed preliminary data from two eye-tracking paradigms that have been used in several previous infant studies; a face â&#x20AC;&#x2DC;pop-outâ&#x20AC;&#x2122; task, to measure proportion of time looking at faces, and a gap/overlap task, to measure the disengagement effect (response time in baseline versus overlap). At 5 months of age, infants with TSC show increased peak looking time to faces compared to typical infants, associated with younger age at seizure onset. Conversely, infants with TSC show longer disengagement times on the gap/overlap task from 10 months of age compared to typical infants, which is associated with increased ASD symptoms at 14 months of age. Conclusion: These preliminary findings indicate atypical social and non-social visual attention from the first year of life in TSC, suggesting early developmental changes that may be associated with epilepsy features. Identification of sensitive and objective biomarkers of risk for behavioural and cognitive problems in TSC will aid in directing more specific interventions and in testing the efficacy of novel early intervention targets. Funding: Tuberous Sclerosis Association, University of London Basil Davies Bequest

Neurodevelopmental Disorders

Publication:

Tye C, Varcin KJ, Bolton P & Jeste SS. (2016). Early developmental pathways to autism spectrum disorders in tuberous sclerosis complex. Advances in Autism, 2(2).

Tuberous sclerosis 2000 study

Investigators: Prof Patrick Bolton1,2, Prof John Yates3, Dr Fiona McEwen1,2,4, Dr Charlotte Tye1,2, Dr Elizabeth Shephard1, Dr Holan Liang5,6, Dr Lisa Underwood1, Emma Woodhouse7 & Dr Anna Combes1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL; 3 Department of Medical Genetics, University of Cambridge; 4 Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary, University of London; 5 Great Ormond Street Hospital, London; 6 Institute of Child Health, University College London; 7 Forensic & Neurodevelopmental Sciences, IoPPN, KCL.

Lay Summary: Tuberous sclerosis complex (TSC) is a rare genetic disorder that causes benign tumour-like growths in several organs, including the brain. Individuals with TSC often present with epilepsy, developmental delays, intellectual disability, and are at greater risk of developing autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The TS 2000 Study is a long-term investigation of a cohort of 125 children with TSC recruited between 2001 and 2005 all over the UK. The project aims to characterise early development in TSC, and how the features of TSC develop during childhood and into adulthood. In addition to collecting medical and physical information and conducting genetic testing, we carried out detailed evaluations of IQ and language, and tailored ASD and ADHD assessments in participantâ&#x20AC;&#x2122;s homes, in order to determine how intellectual, cognitive, behavioural and neurological impairments are related to factors such as gender, the type and course of epileptic seizures in early life, the number and distribution of brain lesions, and the nature of the genetic mutation. In the latest phase of the project, we are collecting brain imaging data using electroencephalography (EEG) and magnetic resonance imaging (MRI) to further explore abnormalities in brain structure and function. By providing information on the risk factors that lead to different intellectual, cognitive and psychiatric outcomes, we hope this research will benefit individuals and families affected by TSC, and lead to a better understanding of how ASD and ADHD develop in general. State of Progress: Ongoing Abstract: Background: Tuberous sclerosis complex (TSC) is a rare multisystem genetic disorder that causes tumour-like lesions in the skin, brain, kidneys and other organs, leading to epilepsy and highly variable psychiatric outcomes, including an increased risk for autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The TS 2000 Study is a prospective longitudinal project which aims to characterise the natural history and neuropsychiatric features of TSC using genetic, behavioural, cognitive, and imaging data. Methods: Participants were recruited among newly diagnosed cases of TSC in the UK between 2001 and 2005 (n = 125, aged 0-16 years) and assessed in three study phases.

CAMHS CAG Projects Day 2018

(1) Phase 1 (2001-2006) included genotyping and assessments of epilepsy, physical features, intellectual

outcome, and clinical brain imaging. (2) Phase 2 (2012-2015) entailed updated assessments of epilepsy, sleep, and home environments, as well

as cognitive, neuropsychiatric, behavioural and intellectual outcomes, including specifically designed measures of ASD and ADHD traits. (3) Phase 3 (2015-present) is currently ongoing and aims to explore abnormalities in neural networks

associated with TSC and its behavioural phenotypes. Parent and self-rated questionnaires, and updated epilepsy, ASD/ADHD, IQ and language assessments were administered. Cognitive processing and attention in response to visual stimuli and social cues were tested using an eye-tracking paradigm, and motor activity levels assessed using actigraph devices. Event-related potentials were measured using electroencephalography (EEG) to investigate electrophysiological responses associated with neurocognitive processes, including face/gaze processing, inhibitory control, emotion processing, and resting-state activity, in response to a variety of tasks probing attention and social cognition. Pilot magnetic resonance imaging (MRI) scans were collected for a small sample of high-functioning participants (n = 19, IQ > 60) using structural, diffusion tensor imaging, and resting-state sequences to assess structural and functional connectivity. Results: Analysis of Phase 1 data provided evidence for the influence of infantile spasms on intellectual development, including a possible causal pathway linking genetic abnormality, cerebral lesion count, epilepsy severity, and intellectual outcome. Recommendations for early diagnosis and management of TSC were proposed, in particular regarding the importance of genetic testing. Phase 2 generated results on the prevalence and distribution of ASD and subthreshold autistic traits in the cohort, as well as ASD and ADHD comorbidity. With the use of other similarly acquired datasets in ASD, ADHD, and ASD+ADHD groups, the correlates and risk factors that are specific to ASD, ADHD and TSC are being examined. Analysis of Phase 3 clinical, behavioural, and imaging data is ongoing. Projects include examining electrophysiological markers of functional neural network abnormalities and examining associations between such network atypicalities and intellectual ability, epilepsy, and symptoms of ASD and ADHD, mapping the structural brain changes in TSC including quantitative lesion mapping, structural connectivity analysis using diffusion tensor imaging, and correlations with clinical, behavioural, and cognitive measures. Conclusion: TS 2000 is the first detailed prospective study of the natural history of TSC, and provides a unique opportunity to further current knowledge of TSC as well as ASD and ADHD aetiology. The large amounts of high quality data collected will ultimately yield further insights into developmental trajectories in TSC, risk factors for psychiatric outcomes, and the relationship between abnormal brain development and behavioural phenotypes. Funding: This project is supported by the Tuberous Sclerosis Association, the Isaac Newton Trust, Autism Speaks, the Baily Thomas Charitable Fund, and Action Medical Research. Publications: 1.

Bolton PF, Clifford M, Tye C, Maclean C, Humphrey A, Le Marechal K, ... & Tuberous Sclerosis 2000 Study Group. (2015). Intellectual abilities in tuberous sclerosis complex: Risk factors and correlates from the Tuberous Sclerosis 2000 Study. Psychological Medicine, 45(11): 2321-2331. Humphrey A, MacLean C, Ploubidis GB, Granader Y, Clifford M, Haslop M, ... & Tuberous Sclerosis 2000 Study Group. (2014). Intellectual development before and after the onset of infantile spasms: a controlled prospective longitudinal study in tuberous sclerosis. Epilepsia, 55(1): 108-116.

Neurodevelopmental Disorders

Tye C, Thomas L, Sampson J, Lewis J, O’Callaghan FO, Yates J & Bolton P. (Accepted). Secular changes in severity of intellectual disability in tuberous sclerosis complex: A reflection of improved identification and treatment of epileptic spasms? Epilepsia Open. 4. Yates JR, MacLean C, Higgins JNP, Humphrey A, le Maréchal K, Clifford M, ... & Bolton PF. (2011). The Tuberous Sclerosis 2000 Study: Presentation, initial assessments and implications for diagnosis and management. Archives of Disease in Childhood, 96(11): 1020-1025.

Developmental neuroimaging in ADHD and related disorders: From biomarker search to neurotherapies

Investigators: Prof Katya Rubia & collaborators Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL). Lay Summary: We use neuroimaging, neurocognitive and psychopharmacological methods to better understand the cognitive, brain and pharmacological deficits of attention-deficit/hyperactivity disorder (ADHD) and related childhood disorders. We also investigate the effects of existing and novel drugs on the brain function and brain chemistry of ADHD and related disorders. Our search for biomarkers for ADHD and related disorders has led to translational neuroimaging studies that are relevant for clinical purposes. We test whether we can diagnose ADHD and ASD patients based on brain structure or function scans and we develop novel neurotherapies that use the regions we found to be abnormal in our biomarker research as targets for novel, brain-based treatments for ADHD such as functional magnetic resonance imaging (fMRI) neurofeedback or brain stimulation. (1) Biomarker research in ADHD and related disorders.

The main goal of our research is to understand how brain structure and function in ADHD and in related childhood disorders differ from normal brain development, and how they differ between each other. We think that a better understanding of the disorder-relevant and disorder-specific underlying brain deficits will ultimately lead to more targeted treatment development, be it pharmacological or non-pharmacological. For this purpose, we conduct structural and functional MRI studies in ADHD, in autism spectrum disorder (ASD), and in obsessive-compulsive disorder (OCD) to understand the brain abnormalities that are underlying each disorder and to elucidate the brain abnormalities that are disorder-specific to each disorder compared to other disorders. We have also conducted several comparative meta-analyses of structural and functional deficits in these disorders to get a wider picture on the most consistent differences in their underlying brain abnormalities. Please see the following project summaries for further details: • •

Specificity of brain deficits: Comparing brain abnormalities between ADHD, ASD and OCD (page 50) Functional maturation abnormalities in autism spectrum disorder relative to healthy controls and ADHD patients (page 53)

(2) Pharmacological neuroimaging studies

We conduct several pharmacological neuroimaging studies using fMRI and positron emission tomography (PET) to understand the underlying mechanisms of action of drugs that are typically used as well as of novel drugs in ADHD and in autism. The aim of these studies is to elucidate the

CAMHS CAG Projects Day 2018

underlying neurotransmitter abnormalities in ADHD and ASD and to understand the effects of drugs that are given to ADHD and ASD on their brain function and brain chemistry. A better understanding of the underlying neurochemical abnormalities in ADHD and ASD and a better understanding of the mechanism of action of existing and novel drugs on their brain function and chemistry will help the development of better pharmacological treatments in the future. Current and future studies include the investigation of Methylphenidate, Atomoxetine, Fluoxetine, Guanfacine and Lisdexamfetamine on brain function in ADHD (and ASD) using fMRI and of the effects of stimulant medication on the opioid system in ADHD using PET. Please see the following project summaries for further details: • An fMRI study on the effects of the serotonin-agonist Fluoxetine on brain activation in adolescents with ADHD and with autism (page 55) • A pilot PET study to test the effects of opioid release after a single dose of Amphetamines (page57) • Effects of a single dose of Guanfacine and Lisdexamfetamines on brain activation in ADHD children (page 58) (3) Translational neuroimaging: Diagnostic classification of ADHD based on brain imaging

In our translational neuroimaging studies, we use imaging methods for more clinically relevant applications. We use pattern recognition analyses to test whether we can make individual diagnostic predictions of ADHD based on their brain structure and function patterns. Please see the following project summary for further details: •

Diagnosing ADHD patients based on brain structure and function patterns (page 60)

(4) Translational neuroimaging: Neurotherapeutics

In our neurotherapeutics studies, we use the neuroimaging biomarkers we have established over the past 25 years as targets for the development of novel, brain-based treatments for ADHD. We use two relatively novel brain therapies, fMRI neurofeedback, which trains patients to self-regulate specific brain regions via neurofeedback methods and non-invasive brain stimulation, transcranial direct current stimulation, which upregulates those brain regions that are not working well in ADHD via the induction of small side-effect free electric currents. Please see the following project summaries for further details: • A proof of concept study of fMRI neurofeedback in ADHD adolescents (page 62) • A large placebo-controlled randomised controlled trial of the efficacy of fMRI neurofeedback in ADHD children (page 64) • A novel neurotherapy of transcranial direct current stimulation combined with cognitive training in ADHD children (page 66)

Specificity of brain deficits: Comparing brain abnormalities between ADHD, ASD and OCD

Investigators: Prof Katya Rubia1, Dr Anastasia Christakou2, Dr Clodagh Murphy3,4, Dr Vincent Giampietro5, Dr Luke Norman1,6, Dr Christina Carlisi1,7, Prof David Mataix-Cols8, Prof Declan Murphy4,9 & Prof Michael Brammer5 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Centre for Integrative Neuroscience & Neurodynamics, University of Reading; 3 Behavioural and Developmental Psychiatry Clinical Academic Group, Behavioural Genetics Clinic, Adult Autism and ADHD Service, South London and Maudsley Foundation NHS Trust, London, United Kingdom; 4 Department of Forensic and Neurodevelopmental Sciences, IoPPN, KCL; 5 Department of Neuroimaging, IoPPN, KCL; 6 Department of Psychiatry, University of Michigan, USA; 7 Division of Psychology & Language Sciences, University College London; 8 Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Instituet, Sweden; 9 Sackler Institute for Translational Neurodevelopment, IoPPN, KCL.

Neurodevelopmental Disorders

Lay Summary: In this study we are interested in the specificity of the brain function deficits in children with attentiondeficit/hyperactivity disorder (ADHD) compared to children with other disorders such as autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). For this purpose, we conduct several meta-analyses comparing brain structure and function deficits in ADHD compared to other disorders and we conduct fMRI comparisons between these disorders using tasks of sustained attention and of reward-based decision making. The main goal is to understand whether the brain abnormalities we observe in ADHD are similar or different to those in ASD or OCD. State of Progress: Completed Abstract: Background: ADHD patients have key abnormalities in fronto-striatal systems of self-control and of attention and of reward-based decision making. However, other childhood disorders such as autism and OCD also have fronto-striatal brain deficits and are impaired in tasks of self-control, attention and reward-based decision making. Methods: We conducted comparative meta-analyses of structural MRI studies and of fMRI studies of inhibitory control between ADHD and OCD and between ADHD and ASD. In addition, we compared 20 boys with ADHD, 20 boys with OCD, 20 boys with ASD and 20 healthy controls in their brain activation while they performed tests of sustained attention and of rewardâ&#x20AC;&#x201C;based decision making (temporal discounting and gambling tasks). Results: The meta-analyses showed that ADHD patients have disorder-specific deficits in the structure of the right basal ganglia and insula relative to OCD and ASD patients. Furthermore, they have disorderspecific deficits in the function of right inferior frontal cortex during tasks of cognitive control relative to OCD and ASD patients. OCD and ASD patients are far more similar to each other with few disorder-specific deficits and share deficits in brain structure and brain function in medial frontal regions which are crucial for top-down control of orbitofronto-limbic affect control systems. During sustained attention, ADHD and OCD and ADHD and ASD patients share abnormalities in fronto-parieto-temporal regions of attention and during reward-based decision making, they share abnormalities in orbitofrontal and ventral striato-limbic regions of motivation and reward. Some differences were observed with lateral frontal regions being more impaired in ADHD and medial frontal regions being more impaired in OCD and ASD. Conclusion: The meta-analysis shows that ADHD patients have disorder-specific deficits in the structure of the basal ganglia and insula and in the function of right inferior frontal cortex relative to OCD and ASD in the context of self-control functions. The individual studies show that for sustained attention, ADHD patients also have disorder-specific lateral prefrontal abnormalities while OCD patients have more medial frontal deficits. For reward-based decision making, however, these childhood disorders have relatively similar abnormalities in ventromedial fronto-striato-limbic reward processing systems. The findings show that the specificity of deficits between disorders is context-specific with self-control and attention systems eliciting disorder-specific lateral frontal deficits in ADHD and more medial frontal deficits in ASD and OCD. Reward-based decision-making systems seem to be impaired in a more similar way across disorders. Overall, ADHD differs more relative to ASD and OCD than the two other disorders relative to each other in their brain abnormalities.

CAMHS CAG Projects Day 2018

Funding: Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and King’s College London and MRC AIMS. Publications: 1.

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Norman L, Carlisi C, Lukito S, Hart H, Mataix-Cols D, Radua JD & Rubia K. (2016). A comparative meta-analysis of structural and functional brain abnormalities in ADHD and OCD. JAMA Psychiatry, 73: 815-825. Carlisi CO, Norman LJ, Lukito S, Radua J, Mataix-Cols D & Rubia K. (2017). Comparative multimodal meta-analysis of structural and functional brain abnormalities in autism Spectrum Disorder and Obsessive-Compulsive Disorder. Biological Psychiatry, 82(2): 83-102. Carlisi CO, Norman L, Murphy CM, Christakou A, Chantiluke K, Giampietro V, Simmons A, Brammer M, Murphy DG, Mataix-Cols D & Rubia K. (2017). Disorderspecific and shared brain abnormalities during vigilance in autism and obsessivecompulsive disorder. Biological Psychiatry Cognitive Neuroscience and Neuroimaging (CNNI), 2(8): 644-654. Carlisi CO, Norman LJ, Murphy CM, Christakou A, Chantiluke KC, Giampietro VP, Simmons A, Brammer MJ, Murphy DG, Mataix-Cols D & Rubia K. (2017). Comparison of neural substrates of temporal discounting between youth with autism spectrum disorder and with obsessive-compulsive disorder. Psychological Medicine, 47(14): 2513-2527 Carlisi CO, Norman LJ, Murphy CM, Christakou A, Chantiluke KC, Giampietro VP, Simmons A, Brammer MJ, Murphy DG, Mataix-Cols D & Rubia K. (2017). Shared and disorder-specific neurocomputational mechanisms of decision-making in autism spectrum disorder and obsessive-compulsive disorder. Cerebral Cortex, 27(12): 5804-5816 Norman LJ, Carlisi CO, Christakou A, Chantiluke K, Murphy C, Simmons A, Giampietro V, Brammer M, Mataix-Cols D & Rubia K. (2017). Neural dysfunction during temporal discounting in paediatric attention-deficit/hyperactivity disorder and obsessivecompulsive disorder. Psychiatry Research Neuroimaging, 269: 97-105 Norman LJ, Carlisi CO, Christakou A, Cubillo A, Murphy CM, Chantiluke K, Simmons A, Giampietro V, Brammer M, Mataix-Cols D & Rubia K. (2018). Shared and disorderspecific task-positive and default mode network dysfunctions during sustained attention in paediatric attention-deficit/hyperactivity disorder and obsessive/compulsive disorder. Neuroimage, 15: 181-193 Norman LJ, Carlisi CO, Christakou A, Murphy CM, Chantiluke K, Giampietro V, Simmons A, Brammer M, Mataix-Cols D & Rubia K. (2018). Fronto-striatal dysfunction during decision-making in attention-deficit/hyperactivity disorder and obsessivecompulsive disorder. Biological Psychiatry, Cognitive Neuroscience and Neuroimaging (CNNI), in press. Christakou A, Murphy C, Chantiluke K, Cubillo A, Smith AB, Daley E, Ecker C, Giampietro V, Murphy D & Rubia K. (2013). Disorder-specific functional abnormalities during sustained attention in youth with attention deficit hyperactivity disorder (ADHD) and with autism. Molecular Psychiatry, 8(2): 236-44 Lim L, Cubillo A, Smith A, Chantiluke K, Marquand A, Simmons A, Mehta M & Rubia K. (2013): Disorder-specific predictive classification of adolescents with attention deficit hyperactivity disorder (ADHD) relative to autism using structural magnetic resonance imaging. PLOS One 8(5):e63660. Lim L, Chantiluke K, Cubillo AI, Smith A, Simmons A, Mehta M & Rubia K. (2014). Disorder-specific grey matter deficits in attention deficit hyperactivity disorder relative to autism spectrum disorder. Psychological Medicine, 17:1-12. Hoogman M, Bralten J, Hibar DP, Mennes M, Zwiers MP, Schweren LS, van Hulzen KJ, Medland SE, Shumskaya E, Jahanshad N, Zeeuw P, Szekely E, Sudre G, Wolfers T, Onnink AM, Dammers JT, Mostert JC, Vives-Gilabert Y, Kohls G, Oberwelland E, Seitz J, Schulte-Rüther M, Ambrosino S, Doyle AE, Høvik MF, Dramsdahl M, Tamm L, van Erp TG, Dale A, Schork A, Conzelmann A, Zierhut K, Baur R, McCarthy H, Yoncheva

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YN, Cubillo A, Chantiluke K, Mehta MA, Paloyelis Y, Hohmann S, Baumeister S, Bramati I, Mattos P, Tovar-Moll F, Douglas P, Banaschewski T, Brandeis D, Kuntsi J, Asherson P, Rubia K, et al. (2018). Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional megaanalysis. Lancet Psychiatry 4(4):310-319. van Rooij D, Anagnostou E, Arango C, Auzias G, Behrmann M, Calderoni S, Daly EM, Deruelle C, DiMartino A, Dinstein I, Durston S, Ecker C, Fair D, Fedor J, Fitzgerald J, Freitag CM, Gallagher L, Gori I, Haar S, Hoekstra L, Rubia K & 22 others. (2017). Cortical and subcortical brain morphometry differences between patients with autism spectrum disorders (ASD) and healthy individuals across the lifespan: Results from the ENIGMA-ASD working group. The American Journal of Psychiatry, 175(4):359-369. Radua J, Rubia K, Canales EJ, Pomarol-Clotet E, Fusar-Poli P & Mataix-Cols D. (2014). Anisotropic kernels for coordinate-based meta-analyses of neuroimaging studies. Frontiers in Psychiatry, https://doi.org/10.3389/fpsyt.2014.00013 Chantiluke K, Barrett N, Giampietro V, Brammer M, Simmons A, Murphy D & Rubia K. (2013). Inverse effect of fluoxetine on medial prefrontal cortex activation during reward reversal in ADHD and autism. Cerebral Cortex, 25(7):1757-70. Chantiluke K, Barrett N, Giampietro V, Santosh P, Brammer M, Simmons A, Murphy DG & Rubia K (2014). Inverse fluoxetine effects on inhibitory brain activation in noncomorbid boys with ADHD and with ASD. Psychopharmacology, 232 (12), 2071-2082 Chantiluke K, Barrett N, Giampietro V, Brammer M, Simmons A, Murphy DG & Rubia K. (2014). Disorder-dissociated effects of fluoxetine on brain function of working memory in attention deficit hyperactivity disorder and autism spectrum disorder. Psychological Medicine, 8:1-11.

Functional maturation abnormalities in autism spectrum disorder relative to healthy controls and ADHD patients

Investigators: Prof Katya Rubia1, Dr Clodagh Murphy2,3, Dr Anastasia Christakou4, Dr Vincent Giampietro5, Prof Michael Brammer5 & Prof Declan Murphy3,6 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Behavioural and Developmental Psychiatry Clinical Academic Group, Behavioural Genetics Clinic, Adult Autism and ADHD Service, South London and Maudsley Foundation NHS Trust, London, United Kingdom; 3 Department of Forensic and Neurodevelopmental Sciences, IoPPN, KCL; 4 Centre for Integrative Neuroscience & Neurodynamics, University of Reading; 5 Department of Neuroimaging, IoPPN, KCL, 6 Sackler Institute for Translational Neurodevelopment, IoPPN, KCL.

Lay Summary: The study investigates the association between age and brain activation in two cohorts of children and adult patients with autism and with attention-deficit/hyperactivity disorder (ADHD) compared to healthy children and adolescents. The aim is to establish whether the brain abnormalities in fMRI in these patient groups during tasks of sustained attention and reward-based decision making are associated with an abnormal functional maturation of the brain compared to healthy controls and to each other. We found that the reduced activation of brain regions that mediate sustained attention and temporal discounting in people with ASD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of autism. State of Progress: In progress.

CAMHS CAG Projects Day 2018

Abstract: Background: Despite evidence of atypical structural brain development in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), investigation of functional brain maturation in people with ASD and ADHD is lacking. This cross-sectional developmental fMRI study investigates the neural substrates underlying performance on a sustained attention task, a temporal discounting task and a gambling task in male adolescents and adults with ASD, with ADHD and in age, sex, and IQmatched typically developing healthy controls. Most importantly, we assess group differences in the neurofunctional maturation of temporal discounting across childhood and adulthood. Methods: Forty-six adolescents with ASD aged 11-35 years old and 44 healthy age matched controls were scanned in fMRI while they performed 3 tasks: a task of sustained attention, and two tasks of reward â&#x20AC;&#x201C;based decision making, a temporal discounting and a gambling task. The fMRI data were compared between groups and we also analysed the association between age and brain activation and compared this between the groups to test whether ASD patients had different maturation of their brain function than healthy controls. An additional cohort of 40 children and adults with ADHD have been scanned in the same tasks and data will be analysed. Results: Adolescent and adult males with ASD had significantly poorer task performance in all tasks and significantly lower brain activation in typical frontal, striatal, parietal and temporal regions that mediate sustained attention and predominantly right hemispheric regions of lateral prefrontal cortices, ventromedial prefrontal cortex, striato-limbic regions, and cerebellum that mediate temporal discounting. Data on the gambling task are still to be analysed. Importantly, reduced activation in key regions of sustained attention and of temporal discounting were associated with abnormal functional brain maturation; controls, compared to people with ASD, showed progressively increasing activation with increasing age in these regions. These differences in the functional maturation of attention and temporal discounting systems were furthermore associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Conclusion: The findings provide first cross-sectional evidence that reduced activation of brain regions that mediate sustained attention and temporal discounting in people with ASD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of autism. The comparison with the data in ADHD will elucidate differences in the functional maturation between ADHD and ASD. Funding: Medical Research Council, MRC AIMS, and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. Publications: 1.

Murphy C, Christakou A, Daly EM, Ecker C, Giampietro V, Brammer M, Smith AB, Johnston P, Robertson DM, MRC AIMS Consortium, Murphy DG & Rubia K. (2014). Abnormal functional activation and maturation of fronto-striato-temporal and cerebellar regions in autistic spectrum disorder during sustained attention. American Journal of Psychiatry, 171:1107-1116. Murphy CM, Christakou A, Giampietro V, Brammer M, Daly EM, Ecker C, Johnston P, Spain D, Robertson DM, MRC AIMS consortium, Murphy DG & Rubia K. (2017).

Neurodevelopmental Disorders

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder. Human Brain Mapping, 38(11):5343-5355.

An fMRI study on the effects of the serotonin-agonist Fluoxetine on brain activation in adolescents with ADHD and with autism

Investigators: Prof Katya Rubia1, Dr Kaylita Chantiluke1, Dr Anna Smith2, Prof Paramala Santosh1, Dr Vincent Giampietro3 & Prof Declan Murphy4,5 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Anxiety Disorders Residential Unit, South London and Maudsley NHS Foundation Trust; 3 Department of Neuroimaging, IoPPN, KCL; 4 Department of Forensic and Neurodevelopmental Sciences, IoPPN, KCL; 5 Sackler Institute for Translational Neurodevelopment, IoPPN, KCL.

Lay Summary: Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficits in Dopamine and Noradrenaline. However, Serotonin has also been involved in ADHD and in impulsiveness as well as in autism spectrum disorder (ASD). We know that dopamine and noradrenaline agonists improve the brain function of ADHD children, in particular of frontal regions that are important for attention and self-regulation. However, nothing is known on whether serotonin agonists have a positive effect on the brain activity in people with ADHD or with autism. The aim of this study was to investigate the effect of a single acute dose of a serotonin agonist, Fluoxetine, on brain function during tasks in which children with ADHD and with high functioning ASD typically have problems with. Functional magnetic resonance imaging was used to scan 20 children with ASD and 20 children with ADHD in a double-blind, randomised controlled design, under either placebo or one acute clinical dose of Fluoxetine (10mg), while performing a Stop Task, a Reversal Task, and a Working memory task. We found that children with ADHD and with ASD under placebo had differences in their brain abnormalities relative to controls and each other. ADHD patients had specific deficits in fronto-striatal systems during motor inhibition, while ASD children had specific deficits in medial frontal regions during reversal learning. During working memory both disorders shared dorsolateral prefrontal deficits. Fluoxetine had different, disorder-specific but positive effects on improving and even normalising the activity of frontal and other brain regions in both ADHD and autism. The effects of improving and normalising brain function deficits in ADHD were similar to those we previously observed with stimulant (Methylphenidate) and non-stimulant drugs (Atomoxetine) during the same tasks, suggesting that a serotonin agonist has similar beneficial effects to the more classic drugs on the activity of the brain of ADHD patients. The findings suggest that serotonin agonists have positive effects on the brain activity in ADHD and ASD and should be further investigated. State of Progress: Completed Abstract: Background: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and share performance and brain abnormalities during tasks of motor inhibition, of reversal learning and of working memory. Serotonin agonists have shown a beneficial effect on the performance on these tasks and there is evidence of positive behavioural effects of serotonin agonists in both

CAMHS CAG Projects Day 2018

disorders. We therefore used functional magnetic resonance imaging (fMRI) to investigate shared and disorder-specific brain abnormalities during these tasks in the two disorders, as well as to test the shared and disorder-specific effects of a single dose of the serotonin agonist fluoxetine on these brain abnormalities. Methods: Age-matched boys with ADHD (18), ASD (19) and controls (25) were compared with fMRI during a working memory, a motor inhibition and a reversal learning tasks. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Healthy controls were only scanned once. We tested for differences between the two patient groups in brain activation during each task and for shared or different drug effects on performance and brain function. To test for normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls. We also tested effects of acute Fluoxetine in ADHD only during a temporal discounting task. Results: Under placebo, relative to controls, both ADHD and ASD boys shared under-activation in right dorsolateral prefrontal cortex during the working memory task. During reward reversal learning, only ASD boys had a deficit in medial frontal cortex relative to healthy controls. During the inhibition task, the two disorders had different abnormalities: ADHD boys had reduced fronto-striatal activation relative to controls and ASD boys had abnormally increased frontal activation. During working memory, Fluoxetine significantly normalised the dorsal prefrontal under-activation in ASD relative to controls while it increased the ability to switch off mind wandering brain regions in ADHD. During the reward reversal task, Fluoxetine normalised the medial frontal deficit that was observed in autism, but decreased activation in this region in ADHD. During the motor inhibition task, Fluoxetine improved and normalised most frontal and other brain activation deficits in both disorders. In ADHD, during the temporal discounting task Fluoxetine upregulated the activation of frontal and basal ganglia regions and downregulated the activation of the default mode regions that are associated with mind-wandering. Conclusion: The findings show that ADHD and ASD have mostly different brain abnormalities during executive function tasks. Fluoxetine had differential effects on the brain abnormalities in the two disorders. However, the single dose of Fluoxetine had a positive effect of improving the brain abnormalities in each disorder, shifting it towards the level of activation in healthy children. The findings suggest that serotonin plays a role in the abnormal brain activation in children with ADHD and with ASD, but that they likely have different baseline serotonin levels as serotonin had differential and in several tasks with opposite effects on the brain activation in the two disorders. Serotonin agonists should therefore be studied more in both disorders. Funding: Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. Publications: 1.

Chantiluke K, Barrett N, Giampietro V, Brammer M, Simmons A, Murphy D & Rubia K. (2013). Inverse effect of fluoxetine on medial prefrontal cortex activation during reward reversal in ADHD and autism. Cerebral Cortex, 25(7):1757-70. Chantiluke K, Barrett N, Giampietro V, Santosh P, Brammer M, Simmons A, Murphy DG & Rubia K. (2014). Inverse fluoxetine effects on inhibitory brain activation in noncomorbid boys with ADHD and with ASD. Psychopharmacology, 232(12): 2071-2082. Chantiluke K, Barrett N, Giampietro V, Brammer M, Simmons A, Murphy DG & Rubia K. (2014). Disorder-dissociated effects of fluoxetine on brain function of working memory

Neurodevelopmental Disorders

in attention deficit hyperactivity disorder and autism spectrum disorder. Psychological Medicine, 8: 1-11. 4. Carlisi C, Chantiluke K, Norman L, Christakou A, Barrett N, Giampietro V, Brammer M, Simmons A & Rubia K. (2016). The effects of acute fluoxetine administration on temporal discounting in youth with ADHD. Psychological Medicine, 28: 1-13. 5. Chantiluke K, Christakou A, Murphy CM, Giampietro V, Daly EM, Ecker C, Brammer M, Murphy DG; the MRC AIMS Consortium & Rubia K. (2014). Disorder-specific functional abnormalities during temporal discounting in youth with attention deficit hyperactivity disorder (ADHD), autism and comorbid ADHD and autism. Psychiatry Research, 223(2): 113-20.

A pilot PET study to test the effects of opioid release after a single dose of amphetamines

Investigators: Prof Katya Rubia1, Dr Alessandro Colasanti2, Dr Ilan Rabiner3, Prof Philip Asherson4, Bartosz Helfer4 & Dr Steve Lukito1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Brighton and Sussex Medical School; 3 IMANOVA Centre for Imaging Sciences; 4 Department of Social Genetic & Developmental Psychiatry, IoPPN, KCL.

Lay Summary: The aim of the project is to use positron emission tomography (PET) to compare attention-deficit/ hyperactivity disorder (ADHD) adults and healthy adults with respect to their baseline opioid levels and their release of opioids after a single acute dose of the stimulant Dexamphetamine. It has been shown that in healthy adults there is a release of opioids after a single dose of stimulant medication in fronto-striato-limbic brain regions. The findings suggest that the gold-standard treatment for ADHD, stimulant medication may work not just by affecting the dopamine system but also the opioid system. This is important as it would suggest that the opioid system is involved in ADHD. The opioid system is very important for reward and motivation, which is typically abnormal in ADHD, and is also implicated in substance abuse, which is typically more pronounced in patients with ADHD. There is also evidence that the opioid system is abnormal in impulsive people. However, no one has tested whether opioid levels are abnormal in ADHD or whether the release of opioids after a stimulant is different in ADHD patients compared to healthy adults. Preliminary findings show that the baseline opioid release in ADHD is different in a brain region that is crucial for cognitive and motivation control and that stimulants lead to a blunted opioid release in ADHD patients relative to healthy adults. State of Progress: Data collection is complete, analyses are ongoing. Abstract: Background: The opioid system has been involved in impulsiveness and motivation control which are key abnormalities in ADHD. The established view is that psychostimulant medication, the goldstandard treatment for Attention Deficit Hyperactivity Disorder (ADHD), acts via dopamine and norepinephrine systems, which are abnormal in the disorder. We have recently, however, shown that in healthy adults, the stimulant dexamphetamine releases endogenous opioids in fronto-striatolimbic regions. This is interesting as stimulants have addictive potential and opioids are thought to mediate the subjective rewarding effects of stimulants, together with Dopamine release. This raises the possibility that abnormalities of the opioid system are linked to the treatment response in ADHD, which would be ground-breaking as it would implicate a novel neurotransmitter system in the disease

CAMHS CAG Projects Day 2018

mechanism of ADHD and in the mechanism of action underlying stimulant medication. Methods: This study proposes to carry out the first direct examination of the brain opioid system in ADHD, using [11C]Carfentanil PET (positron emission tomography) which measures mu-opioid receptor availability and mu-opioid release after a single drug challenge. We will test whether 6 ADHD adults relative to 30 healthy control adults have abnormalities in endogenous opioid release after a single dose of a stimulant and in their baseline opioid system in fronto-striato-limbic areas by scanning them with [11C]Carfentanil PET, at baseline and after a single challenge dose of Dexamphetamine. Opioid measures will be related to ADHD-associated clinical features, cognitive impairments and subjective response to Dexamphetamine. The study is a multidisciplinary collaboration between experts of ADHD and of stimulants and PET experts of the opioid system. Results: Preliminary findings suggest that in ADHD patients there is opioid release in basal ganglia regions after a single dose of Dexamphetamine, similar to that in healthy adults. However, in the anterior cingulate cortex, ADHD patients relative to healthy controls have lower baseline opioid levels and a reduced opioid release after the single dose of Dexamphetamine. Conclusion: The findings show for the first time that the opioid system in ADHD may be different in a brain region that is crucial for cognitive and motivation control and that stimulants may lead to a blunted opioid release in ADHD patients in the same region (the anterior cingulate). The findings of a blunted opioid release in ADHD adults after stimulants could potentially suggest that there is less addictive potential to stimulants in ADHD relative to healthy subjects. Funding: The National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and King’s College London. Publications: 1.

Colasanti A, Searle GE, Long CJ, Hill SP, Reiley RR, Quelch D, Erritzoe D, Tziortzi AC, Reed LJ, Lingford-Hughes AR, Waldman AD, Schruers KR, Matthews PM, Gunn RN, Nutt DJ & Rabiner EA. (2012). Endogenous opioid release in the human brain reward system induced by acute amphetamine administration. Biological Psychiatry, 72(5): 371-7. Fusar-Poli P, Rubia K, Rossi G, Sartori G & Ballotin U. (2012). Striatal dopamine transporter alterations in ADHD: Pathophysiology of adaptation to psychostimulants? A meta-analysis. American Journal of Psychiatry, 169: 264 –272

Effects of a single dose of Guanfacine and Lisdexamfetamines on brain activation in ADHD children

Investigators: Prof Katya Rubia1, Oliwia Kowalczyk1, Prof Mitul Mehta2, Prof Paramala Santosh1, Dr Celine Ryckaert1 & Dr Dennis Ougrin1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL.

Lay Summary: The aim of this project is to understand the mechanisms of action of two novel pharmacological drugs 58

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for ADHD, a stimulant drug called Lisdexamfetamine and a non-stimulant drug called Guanfacine, on the brain function in these children. We have previously found that the noradrenaline agonist Atomoxetine had shared and drug-specific effects compared to the dopamine agonist Methylphenidate. In this study, we wanted to understand the mechanisms of action of these newer drugs for ADHD and how they compare to the effects we have observed with the older drugs Methylphenidate and Atomoxetine. For this purpose, we will compare single dose effects of Guanfacine extended release (GXR) and Lisdexamfetamine (LISDEX) relative to placebo on the brain function of ADHD adolescents in fMRI during typically compromised cognitive tasks that are modulated by these drugs (motor inhibition, working memory and sustained attention). We will test which effects on the brain function are shared between these two drugs and which are specific to each of the drugs and how they compare to the effects we have previously observed with the older ADHD drugs. State of Progress: In progress Abstract: Background: We found that the most common stimulant medication, Methylphenidate, enhances the activation of key prefrontal and basal ganglia regions that are typically under-activated in ADHD patients. The non-stimulant drug Atomoxetine, a second-line treatment for ADHD, had similar effects on improving frontal brain abnormalities in ADHD. The mechanisms of action of novel, more recently licenced stimulant (Lisdexamfetamine) and nonstimulant (Guanfacine Extended Release) drugs on ADHD brain function, are, however, unknown. Lisdexamfetamines has shown in some studies to have stronger effects on improving clinical behaviours than Methylphenidate. Guanfacine, a selective noradrenaline agonist, has also been shown to have stronger clinical effects than the noradrenaline agonist Atomoxetine. Both drugs have shown to improve performance of ADHD patients in cognitive tasks of working memory, attention and cognitive flexibility. In this study, we wanted to test the effects of these two novel recently licenced drugs on the brain function of ADHD children to better understand their mechanisms of action and how they differ from the effects of the older more established drugs such as Methylphenidate and Atomoxetine. Methods: For this purpose, 20 medication-naĂŻve ADHD male adolescents between 10 and 18 years will be scanned 3 times and be randomised to 3 one hourly fMRI scans with one week break in between, under a single dose of Guanfacine, of Lisdexamfetamine and of placebo. They will perform a task of motor inhibition, sustained attention and working memory. We will compare the effects of the two drugs against placebo and each other. Results: Pending Conclusion: We hypothesise that the noradrenaline agonist Guanfacine will be superior to Lisdexamfetamine in enhancing dorsal prefrontal and parietal activation which is mediated by noradrenaline. The dopamine agonist Lisdexamfetamine will be superior to Guanfacine in increasing activation in the inferior frontal and striatal brain regions that are mediated by dopamine during the attention and stop tasks. The findings will help us to understand the different mechanisms these drugs have on the ADHD brain that may be mediating the positive effects on cognitive performance and on ADHD symptoms. Funding Shire pharmaceuticals and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. 59

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Publications: 1.

Rubia K, Halari R, Christakou A & Taylor E. (2009). Impulsiveness as a timing deficit: brain dysfunctions during timing in attention deficit hyperactivity disorder and normalisation with Methylphenidate. Philosophical Transactions of the Royal Society B: Biological Sciences, 364: 1919-193 2. Rubia K, Halari R, Mohammad M & Taylor E. (2009). Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task. Psychopharmacology, 57: 640–652 3. Rubia K, Halari R, Cubillo A, Smith A, Mohammad M, Brammer M & Taylor E. (2011). Methylphenidate normalises fronto-striatal underactivation during interference inhibition in medication-naive boys with attention-deficit hyperactivity disorder. Neuropsychopharmacology, 36(8): 1575–1586. 4. Rubia K, Halari R, M Mohammad, Taylor E & Brammer M. (2011). Methylphenidate normalises fronto-cingulate underactivation during error processing in attention-deficit hyperactivity disorder. Biological Psychiatry, 70: 255-262. 5. Smith A, Cubillo A, Barrett N, Giampietro V, Simmons A, Brammer M & Rubia K. (2013). Differential neurofunctional effects of methylphenidate and atomoxetine in boys with attention deficit hyperactivity disorder during time perception. Biological Psychiatry, 74(8): 615-622. 6. Cubillo A, Smith A, Barrett N, Giampietro V, Simmons A, Brammer M & Rubia K. (2013). Drug-specific frontal laterality effects of Atomoxetine and Methylphenidate in ADHD boys during working memory. Psychological Medicine, 19: 1-14. 7. Cubillo A, Smith A, Barrett N, Giampietro V, Simmons A, Brammer M & Rubia K. (2014). Shared and drug-specific effects of Atomoxetine and Methylphenidate on inhibitory brain dysfunction in medication-naive ADHD boys. Cerebral Cortex, 24(1): 17485. 8. Rubia K, Alegria A, Smith ABS, Cubillo A, Brammer M & Radua Q. (2013). Effects of stimulants on brain function in ADHD: A systematic review and meta-analysis. Biological Psychiatry, 76(8): 616-28.

Diagnosing ADHD patients based on brain structure and function patterns

Investigators: Prof Katya Rubia1, Dr Heledd Hart1, Dr Lena Lim1,2 & Dr Andre Marquand3 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Cognitive Neuroimaging Centre, Nanyang Technical University, Singapore; 3 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Netherland.

Lay Summary: One of the long-term aims of neuroimaging in psychiatric disorders has been to find a more objective, brain-based method of diagnosis. Unfortunately, this promise has not been fulfilled so far, as traditional MRI analyses are based on group statistics and do not lend themselves to make predictions for individual subjects. We have used new analytical methods, called machine learning or multivariate pattern recognition analyses, that use patterns of structural and functional data and can make individual predictions of diagnostic membership to test whether we can diagnose ADHD or ASD patients based on structure and function patterns with reasonable accuracy. We found that we could make diagnostic predictions based on machine learning methods on structural MRI data for ADHD and ASD patients with over 79% accuracy and on functional MRI data of tasks of inhibition and time estimation with an accuracy of over 75%. However, good classification accuracies were found exclusively in homogenous groups of medication-naïve patients with combined-type ADHD. Findings, however, will need to be

Neurodevelopmental Disorders

replicated, applicable to more heterogeneous patient groups and methodologies improved before this can be used to help clinical diagnostic processes. Abstract: Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The studyâ&#x20AC;&#x2122;s aim was to apply Gaussian process classification (GPC) (a machine learning tool) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD). Furthermore, we used the same methodology on fMRI data of tasks of motor inhibition and time estimation to test whether we can accurately diagnose ADHD patients based on fMRI activation patterns. Methods: Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. For fMRI data, 30 adolescent ADHD and 30 age-matched healthy boys underwent fMRI while performing a Stop task, and 20 ADHD adolescents and age matched healthy control boys were scanned while they performed a time discrimination task. Results: The pattern of grey matter correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. For the stop task fMRI data, the pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. For the fMRI data of the time estimation task, the pattern of brain activation correctly classified up to 80% of patients and 70% of controls, achieving an overall classification accuracy of 75%. Conclusions: The study provides evidence that pattern recognition analyses can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed brain structure patterns with 79.3% accuracy and that this is disorder-specific relative to ASD and with 75%-77% accuracy for brain function patterns. The findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD. However, replications are needed across different ADHD patient groups and different centres before this can be used clinically. Publications: 1.

Lim L, Cubillo A, Smith A, Chantiluke K, Marquand A, Simmons A, Mehta M & Rubia K. (2013): Disorder-specific predictive classification of adolescents with attention deficit hyperactivity disorder (ADHD) relative to autism using structural magnetic resonance imaging. PLOS One 8(5):e63660 Hart H, Marquand A, Chantiluke K, Cubillo A, Smith A, Simmons A, Brammer M & Rubia K. (2014) Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD. Human Brain Mapping, 35:3083â&#x20AC;&#x201C;3094. Hart H, Marquand A, Smith A, Cubillo A, Simmons A, Brammer M & Rubia K. (2014). Predictive neurofunctional markers of ADHD based on pattern classification of temporal processing. Journal of Abnormal Child Psychology and Psychiatry, 53(5):569-78

CAMHS CAG Projects Day 2018

A proof of concept study of fMRI neurofeedback in ADHD adolescents

Investigators: Prof Katya Rubia1, Analucia Alegria1, Dr Helen Brinson1, Dr Melanie Wulff1, Dr Marion Criaud1, Dr Vincent Giampietro2, Prof Gareth Barker2, Prof Anthony S. David3, Prof Eric Taylor1, Dr Daniel Stahl4 & Prof Daniel Brandeis5,6,7 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL; 3 Department of Psychosis Studies, IoPPN, KCL; 4 Department of Biostatistics and Health Informatics, IoPPN, KCL; 5 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; 6 Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Switzerland; 7 Center for Integrative Human Physiology and Neuroscience Center Zürich, University of Zürich, Switzerland.

Lay Summary: In this study we tested a new brain therapy for ADHD by targeting a brain region that we found to be abnormally functioning in ADHD in our 25-year research of fMRI neuroimaging. In this proof of concept study, we investigated the feasibility and potential of a new drug-free treatment for ADHD using functional magnetic resonance imaging (fMRI)-neurofeedback that targets their key brain abnormality. Adolescents with ADHD were trained to increase the activity of the right frontal region which is crucial for attention and self-control and which we have shown is not working very well in this patient group. While being scanned in a modern MRI scanner for 4 hours over 2 weeks, they received feedback of their own brain activity which was connected to a videogame. They had to lift a spacerocket from the ground into the sky to reach the stratosphere and planets with their brain activity which was directly connected to the rocket in the video. A control group was trained to increase the activity of another brain region in the identical way. The findings showed that the treatment was feasible, and that ADHD children can learn to self-regulate their own brain activity. Furthermore, better self-regulation of the frontal region was associated with improved ADHD symptoms after the neurotherapy which was even stronger almost a year later. In addition, the ADHD children had better attention skills and improved activity in this brain region of self-control. The findings are hence promising and show that fMRI-neurofeedback of this frontal brain region may be a potential new treatment for ADHD that needs to be further tested. State of Progress: Completed Abstract: Background: This project was a proof of concept study for a novel, non-pharmacological treatment for ADHD, called fMRI-neurofeedback, which we believe might bring benefits over the longer-term without causing side effects. EEG-neurofeedback has been used for over 50 years but has very small effects. FMRI neurofeedback has a better spatial resolution and can target the key regions that are abnormal in ADHD. Children with ADHD have problems with the activation of a particular frontal brain area that is responsible for self-control and attention, the right inferior frontal cortex. This region is also typically enhanced in activation with stimulant medication, the gold-standard treatment for ADHD. The new treatment involves playing a computer game within a MRI scanner that is connected to this frontal brain region. While lying in the scanner, the children can see their own brain activity on the computer disguised in a computer game, and they move the computer game with their own brain activity. With this, they learn to improve the activity of the brain region that is connected to the computer game which is hypothesised to be associated with better clinical symptoms and better cognitive performance in tests of attention. 62

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Methods: We tested in a single blind, randomised controlled study with an active-control group whether fMRIneurofeedback can help children with ADHD improve their self-control and attention skills and improve their ADHD symptoms. Thirty-one 12-18 year-old boys with ADHD were scanned during eleven 8.5-minute treatment runs, in 4 MRI scan hours, in an MRI scanner. During the scanning, they watched a cartoon rocket on a computer screen, which was connected to their own brain activity. If the children managed to increase the brain activity in the frontal region responsible for self-control, the rocket lifted and the children gained points. Through trial and error, the children learn how to control their brain activity and move the rocket. One group of children (18 boys) had to increase the activity of the (right inferior) frontal region of attention and self-control, while the other group had to increase activity in another brain region, the parahippocampal gyrus (control group of 13 boys). We measured improvements in ADHD behaviours, cognitive performance, fMRI brain activation during a task of self-control and side and adverse effects before and after the treatment as well as at about 11 months follow-up. Figure 6. Schematic representation of neurofeedback.

The rocket game used for the fMRI-neurofeedback training and increased activation in right inferior frontal cortex in ADHD adolescents after 11 runs of 8.5 min of fMRI-neurofeedback.

Results: We found that both active and control groups successfully learned to increase the activity of the brain region they were trained on and both groups improved in their ADHD symptoms after relative to before the neurofeedback training. However, only the active group showed a transfer effect, which means they learned to enhance their brain activation without the feedback, which is used as a proxy of learning in real life. Furthermore, only the active group became better in their ability to concentrate and improved in their brain activity during a test of self-control. Furthermore, in the active group the ADHD symptoms improved even further 11 months after the training, who showed a large effect size of clinical improvement, comparable to the effect size of stimulant medication, while the control group only showed a trend-level improvement at 11 months. Conclusion: The study shows therefore for the first time, that ADHD children are able to self-regulate specific brain regions via fMRI-neurofeedback. Furthermore fMRI-neurofeedback has potential as a novel

CAMHS CAG Projects Day 2018

treatment for ADHD children, as it is feasible, safe, has no adverse effects, leads to short-term and longer-term clinical improvements and to better attention and better self-controlled brain function in ADHD adolescents. The longer-term beneficial effects of improving ADHD behaviour which were observed almost a year after the treatment suggest that the treatment may have neuroplastic effects which would make it superior to stimulant medication that does not work longer-term when it is discontinued. Future studies will need to investigate the therapy further to establish its clinical efficacy and rule out potential placebo effects. Funding: Action Medical Research and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and the Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. Publications: 1.

Alegria AA, Wulff M, Brinson H, Barker GJ, Norman LJ, Brandeis D, Stahl D, David AS, Taylor E, Giampietro V & Rubia K. (2017). Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder. Human Brain Mapping. 38(6):31903209. Rubia K, Criaud M, Wulff M, Alegria A, Brinson H, Barker GJ, Brandeis D & Giampietro V. (2018). Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in children with ADHD. Submitted to NeuroImage.

A large placebo-controlled randomised controlled trial of the efficacy of fMRI neurofeedback in ADHD children

Investigators: Prof Katya Rubia1, Dr Marion Criaud1, Dr Steve Lukito1, Ms Sheut-Ling Lam1, Dr Vincent Giampietro2, Prof Emily Simonoff1 & Prof Gareth Barker2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL.

Lay Summary: This project is conducting a large randomised controlled trial of a novel, non-pharmacological treatment for ADHD, called fMRI Neurofeedback, which we believe might bring potential longerlasting benefits without causing side effects. Our neuroimaging research over the past 25 years has shown that children with ADHD have problems with the activation of a particular frontal region of the brain that is responsible for self-control and attention. This new brain-based treatment targets this region of the brain that is not working so well in ADHD children. It involves playing a computer game that is connected to a modern MRI scanner. The children get feedback of their own brain activity in real time in the scanner disguised in a computer game, and while playing the game they will then learn to improve the activity of this brain area. By means of a playful computer game, children are then expected to gain greater control of this region. Our pilot study showed that ADHD patients can learn to enhance their own brain activity in 4 hourly fMRI scans and better self-regulation of this particular frontal region of attention and self-control in ADHD is associated with better clinical symptoms, better brain activation and better attention skills. Furthermore, we found that the effect on improving ADHD behaviour was longer-lasting and even stronger a year after than immediately after the treatment. In this study, we will test the brain treatment in a larger group of 100 ADHD children, and will compare

Neurodevelopmental Disorders

it to a placebo group who receives fake neurofeedback from another person. If the treatment is successful, it will lead to the development of a novel neurotherapy for ADHD which is drug-free, has no side effects and is likely to be longer-lasting than stimulant medication. State of Progress: Ongoing Abstract: Background: Medication helps around 70% of children with ADHD but is associated with side effects such as restricted growth, loss of appetite and disturbed sleep, is not indicated for all children, and there is little evidence that it helps in the longer-term as there may be a brain adaptation to the drug. Our proof of concept study (see above) showed that children with ADHD can learn to self-control the activity in this frontal region and that this is associated with better symptoms, better brain activity during a test of self-control and better performance in an attention test. In this study, we want to test this novel brain therapy more thoroughly in a larger number of 100 ADHD patients and will include a placebo condition. Methods: For this study, 100 boys with ADHD aged 10 to 18 years will undergo 4 fMRI scans of 60 min over 2 weeks, where they will be trained to enhance the activity of the right inferior frontal cortex. This will be achieved in a playful way, by playing a videogame of a rocketeer that is connected to their brain activity. The goal is for the children to manage to fly the rocketeer into the sky where he will see some planets and asteroids and reach a space station. Half of the children will be in a control group who will receive sham neurofeedback where they will obtain non-contingent NF from the NF data of one of the participants of the real neurofeedback group. We will test in a well powered study whether fMRI-NF of a frontal region in ADHD boys will improve their clinical symptoms, their brain activation and their cognitive problems after the treatment as well as after 6 months later to test for longer-term effects. Results: Pending Conclusion: We hypothesise that fMRI Neurofeedback is safe in ADHD children and not associated with any side effects. Furthermore, we hypothesise that the active group will learn to self-regulate the frontal region over the 15 runs of fMRI-NF training and that this increased self-regulation will result in better clinical ADHD symptoms, in better performance in tests of attention, self-regulation and cognitive flexibility and in improved brain activation in frontal regions during a task of self-control. Furthermore, we hypothesise that the self-regulation training will lead to longer-term changes in the brain, which will mean that we will see longer-lasting effects that will be even stronger 6 months after the treatment than immediately after the treatment. If this study is successful, it would be a first step towards developing a novel, brain-based, side-effect free and non-pharmacological treatment for ADHD that could benefit many young people affected by this condition. Funding: Medical Research Council (MRC) Grant MR/P012647/1 to KR Publication: Pending

CAMHS CAG Projects Day 2018

A novel neurotherapy of transcranial direct current stimulation combined with cognitive training in ADHD children

Investigators: Prof Katya Rubia1, Dr Samuel Westwood1, Prof Philip Asherson2, Prof Cohen Kadosh3, Prof Anthony David4 & Prof Bruce Wexler5,6 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL; 3 Department of Experimental Psychology, Oxford University; 4 Department of Psychosis Studies, IoPPN, KCL; 5 Yale School of Medicine, Yale University; 6 Neurocognitive Research Laboratory, the Connecticut Mental Health Center

Lay Summary: This project is conducting a proof of concept randomised controlled trial of a novel, nonpharmacological treatment for ADHD, which consists in transcranial direct current stimulation (tDCS) combined with cognitive training. The novel therapy has the potential to bring lasting benefits without causing side effects. Our biomarker research has shown that children with ADHD have consistent problems with the activation of a particular frontal brain region that is responsible for self-control and attention. The same region is also typically improved in activation with stimulant medication, the gold-standard treatment for ADHD. The new treatment involves non-invasive stimulation of this right (inferior) frontal region of attention and self-control while the children at the same time are getting trained in skills of attention and self-control by playing an adaptive computer game that trains these skills. Several studies have shown that children with ADHD can improve in their symptoms and in their cognitive skills if they receive brain stimulation over frontal regions. It has also been shown that brain stimulation combined with cognitive training can boost the cognitive training effects and lead to longer-term neuroplastic changes. We therefore expect that brain stimulation over a frontal region that is abnormal in ADHD and underlying the mechanism of action of stimulant medication together with cognitive training of skills that are mediated by the same region will result in better skills of attention and self-control and improve ADHD symptoms. TDCS has been shown to be perfectly safe and has minimal side effects like temporary itching over the scalp in a small number of people State of Progress: Ongoing Abstract: Background: Medication helps around 70% of children with ADHD but is associated with side effects such as restricted growth, loss of appetite and disturbed sleep and there is little evidence that it helps in the longer term. Brain stimulation with tDCS has shown to lead to longer-term brain plastic effects because it enhances the firing of neurons and leads to better connections between neurons in the brain. Brain stimulation has also been shown to enhance neurotransmitters such as dopamine that are abnormal in ADHD. Several pilot studies have shown that 1-5 sessions of 20 min of tDCS brain stimulation over frontal regions can improve ADHD symptoms and their cognitive skills. In this study, we want to test this novel brain-based therapy more thoroughly in 40 ADHD patients over 15 sessions of 20 minutes daily for 3 weeks. We chose a frontal region that is key to self-regulation and attention, that has been shown to be under-activated in ADHD in our 25 year neuroimaging research and that we have shown is consistently improved in function with stimulant medication. Also, we will combine brain stimulation with cognitive training as we think that the combination of both will have synergistic effects and achieve better effects than either treatment alone. If successful, this could lead to the development of a novel side-effect free and non-pharmacological treatment for ADHD.

Neurodevelopmental Disorders

Methods: Forty ADHD children, between 10-18 years, will be randomised into a group that receives real tDCS brain stimulation of the right frontal cortex together with cognitive training or sham (fake) brain stimulation with cognitive training. Participants will be asked to perform an engaging computer training task on a tablet developed by Yale University while they receive transcranial direct current stimulation (tDCS) of a small electrical current of 1 mA at the same time they are playing the PC games. The video game increases in difficulty as the player becomes more skilled and has already been shown to improve inattention and impulsivity in children with ADHD. A control group of boys with ADHD will receive exactly the same treatment, except that no electrical current will be passed through the electrodes. By comparing behavioural symptoms in the two groups after treatment, it should be possible to see if brain stimulation with tDCS enhances the effects of the computer game training. The cognitive training and stimulation will last 20 minutes, 5 days a week, for 3 weeks. Before and after the last sessions, electrophysiological recordings will also be obtained to test whether there will be brain changes after the treatment. We will test whether parent ratings of ADHD symptoms will improve and whether the children will improve in their performance of tests of working memory, attention, timing and self-control which are all mediated by the frontal region that was stimulated by the treatment. We will test for improvements in all measures after the training and after 6 months. TDCS is perfectly safe and has not shown any side effects in children. Results: Pending Conclusion: We hypothesise that tDCS brain stimulation of right inferior frontal cortex, a key region of self-control and attention that is dysfunctional in ADHD, combined with cognitive training will improve ADHD symptoms and their cognitive skills in attention, self-control, timing and working memory functions after the training and 6 months later. The study will be a first step towards the development of a new, non-drug treatment for ADHD which is very cheap, could be easily implemented in clinics and could potentially benefit many young people affected by this condition. Figure 7. Combining the brain stimulation and cognitive training in ADHD children

Transcranial direct current stimulation apparatus (left), right inferior frontal gyrus, a brain region typically under-activated in people with ADHD (centre), and the computer training task (right).

Funding: Action Medical Research and Garfield Weston foundation Publication:

Rubia K. (2018). Cognitive neuroscience of attention deficit hyperactivity disorder (ADHD) and its clinical translation. Frontiers in Human Neuroscience, doi: 10.3389/ fnhum.2018.0010 67

CAMHS CAG Projects Day 2018

Digital health monitoring systems for ADHD

Investigators: Dr Johnny Downs1,2, Ms Anna Morris1,2, Dr Argyris Stringaris3, Dr Nick Meyer4, Dr Ian Grant5, Dr Zina Ibhraim5, Prof Richard Dobson5, Prof Edmund Sonuga-Barke1 & Prof Emily Simonoff1,2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 NIHR South London and Maudsley NHS Foundation Trust Biomedical Research Centre; 3 Mood and Brain Development Unit, National Institute of Mental Health, Bethesda, USA; 4 Department of Psychosis Studies, IoPPN, KCL; 5 Department of Biostatistics and Health Informatics, IoPPN, KCL.

Lay Summary: One in twenty-five children have attention deficit hyperactivity disorder (ADHD). To receive a diagnosis, children need to have severe and chronic problems with inattention, impulsivity and hyperactivity, both at school and home. Medication can help. Nearly half of children diagnosed with ADHD in NHS child and adolescent mental health services (CAMHS) are offered medication at primary school age. There are several major problems with how ADHD is managed: (1) current ways of checking for side-effects or whether the medication works are normally via paper-based questionnaires posted to caregivers, and teachers, and so a lot of information never reaches the clinicians on time; (2) teachers and parents assess the same children differently. For doctors, these differences make prescribing the right dose difficult, as they cannot determine who may be more accurate; (3) clinicians and family want to know that ADHD treatments help their child later on. Information is not collected once children leave NHS care, so clinical services cannot show parents that their treatment can make long-term differences at school or home. This research project aims to tackle these issues using digital technologies. The REMAIN study is building and testing an innovative digital system which aims to make completing questionnaires on ADHD symptoms and medication side-effects much easier. It also tests whether wrist-based activity trackers (wearables) and online attention tests, provide a better way of checking medication effects. This study will put specialist healthcare designers alongside children with ADHD, caregivers, clinicians, teachers, data-scientists to try and create the most user-friendly health monitoring system in the NHS. State of Progress: Ongoing Abstract: Research questions: Will an integrated multi-modal digital health monitoring system (DHMS), linked with electronic health records (EHR), improve the monitoring of treatment effectiveness and adverse effects in children with attention deficit hyperactivity disorder (ADHD)? Will it enhance long-term outcome evaluation for ADHD services? Background: Since the 1990’s, use of UK ADHD stimulant medication has increased 34-fold, and is currently being prescribed to 1-in-200 children. Current management of ADHD is challenging: • •

•

Overstretched NHS ADHD clinics cannot meet National guidance on clinical monitoring schedules. Data collection methods for monitoring treatment effectiveness and adverse effects rely on postal returns from teachers/parents, which are inefficient, provide low returns and hinder informed decision making. ADHD rating scales which assess intervention effectiveness are very subjective. Low inter-rater agreement is common, and susceptible to nocebo and placebo effects, which hinders safe and effective practice.

Neurodevelopmental Disorders

Systematic reviews show that monitoring symptoms and adverse effects can be improved by online web-applications, and we have developed an online system called Me_Health_e. ADHD rating subjectivity could be addressed using wearables to provide objective measures of activity and sleep, combined with online neuropsychological tests of attention and impulsivity. No NHS mental health services have integrated these approaches within a user-designed DHMS; the added benefits for these DHMS in assessing treatment effectiveness and safety above current approaches need clarifying. Objectives: The main aim of this study is to investigate if a user-designed DHMS can improve the quality of information available for monitoring treatment effectiveness and safety in childhood ADHD treatment. This will be addressed using qualitative, epidemiological and computational techniques: (1) Qualitative study to optimise the usability of ADHD symptom tracking and adverse effects monitoring. Bringing together multiple stakeholders (parents, children, academics, clinicians, engineers, NHS system engineers) to co-design, plan and implement changes to the objective measurement devices, Me_Health_e system. (2) A prospective cohort study to examine the feasibility and drug target validity of symptom tracking and adverse effects monitoring in ADHD via adapted Me_Health_e and objective measurement systems (wearables and online neuropsychological performance tests) in non-clinic settings at home and school. (3) A data-linkage study to nest the participant cohort into EHR and linked school data to evaluate long-term outcomes. Impacts: Creation of the first validated DHMS for both subjective and objective data collection in home/school settings; ready for trial evaluation in the NHS to its test impact on ADHD treatment effectiveness, adherence and reduction of adverse effects. Cost-savings beyond improving ADHD outcomes, include reduce caregiver, teacher and clinician burden. Provides proof of principle of this DHMS as a secure NHS pipeline to enhance patient reported outcomes which can be readily extended to monitoring other long-term health conditions. Funding: Psychiatry Research Trust Peggy Pollak Fellowship, the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, and Guyâ&#x20AC;&#x2122;s and St Thomas Charity. Publications: Pending

CAMHS CAG Projects Day 2018

Emotional and Behavioural Disorders

CAMHS CAG Projects Day 2018

The origins of cognitive deficits in victimised children

Investigators: Dr Andrea Danese1, 2,3, Prof Terrie E. Moffitt1,4, Prof Louise Arseneault1, Ben A. Bleiberg4, Perry B. Dinardo4, Stephanie B. Gandelman4, Dr Renate Houts4, Antony Ambler1, Dr Helen L. Fisher1, Prof Richie Poulton5 & Prof Avshalom Caspi1,4 1 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Child & Adolescent Psychiatry, IoPPN, KCL; 3 National & Specialist Clinic for Child Traumatic Stress and Anxiety Disorders, South London and Maudsley NHS Foundation Trust; 4 Department of Psychology and Neuroscience and the Department of Psychiatry and Behavioral Sciences, Duke University, North Carolina, USA; 5 Department of Psychology, University of Otago, Dunedin, New Zealand.

Lay Summary: Adults with a history of childhood maltreatment have been shown to differ from individuals without such experiences in measures of brain function. However, it is unclear if such differences indicate clinically relevant deficits in cognitive function, and whether these differences emerge after child maltreatment or are already present before maltreatment exposure. Using prospective data from two birth cohorts totalling more than 3,000 individuals and born 20 years and 20,000 km, we showed that maltreated children have pervasive impairment in several cognitive functions when they reach adolescence or adult life. Of note, these deficits are largely explained by pre-existing cognitive deficits measured before victimisation exposure and, thus, should be interpreted as pre-existing risk factors for child maltreatment rather than its consequences. State of Progress: Completed Abstract: Background: Individuals reporting a history of childhood violence victimisation have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. The authors used data from two large cohort studies to address these research questions directly. Methods: The authors tested the association between prospectively collected measures of childhood violence victimisation and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the U.K. E-Risk Study and 1,037 members of the New Zealand Dunedin Study who were followed up from birth until ages 18 and 38 years, respectively. Multiple measures of victimisation and cognition were used, and comparisons were made of cognitive scores for twins discordant for victimisation. Results: Individuals exposed to childhood victimisation had pervasive impairments in clinically relevant cognitive functions, including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimised individuals were largely explained by cognitive deficits that predated childhood victimisation and by confounding genetic and environmental risks. Conclusion: Findings from two population-representative birth cohorts totalling more than 3,000 individuals and born 20 years and 20,000 km apart suggest that the association between childhood violence victimisation and later cognition is largely non-causal, in contrast to conventional interpretations. These findings support the adoption of a more circumspect approach to causal inference in the 72

Emotional and Behavioural Disorders

neuroscience of stress. Clinically, cognitive deficits should be conceptualised as individual risk factors for victimisation as well as potential complicating features during treatment. Funding: Medical Research Council, U.S. National Institute of Child Health and Development and the Jacobs Foundation Publication:

Danese A, Moffitt TE, Arseneault L, Bleiberg B, Dinardo P, Gadelman S, Houts R, Ambler A, Fisher HL, Poulton R & Caspi A. (2017). The origins of cognitive deficits in victimized children: Implications for neuroscientists and clinicians. American Journal of Psychiatry, 174(4): 349-361 doi: 10.1176/appi.ajp.2016.16030333

Child maltreatment and obesity

Investigators: Dr Andrea Danese1,2,3 1 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Child & Adolescent Psychiatry, IoPPN, KCL; 3 National & Specialist Clinic for Child Traumatic Stress and Anxiety Disorders, South London and Maudsley NHS Foundation Trust.

Lay Summary: Previous experiments in non-human primates suggested that early life stress is associated with later obesity, but observations in humans were inconsistent. Therefore, we carried out a meta-analysis, that is, we pull together all studies looking at this very question. In a meta-analysis of 41 studies with 190,000 participants, we found that maltreated individuals had 36% increase in risk of obesity. Results were not affected by how maltreatment or obesity were measured, nor by the effect of socio-economic status, smoking, alcohol intake, physical activity, or the quality of individual studies. The association was stronger in women and those of White European ancestry. In contrast, it was weaker in studies that statistically accounted for the effect of depression, suggesting that depression may contribute to obesity in maltreated individuals. State of Progress: Completed Abstract: Background: Childhood maltreatment is a known risk factor for mental illness. Increasing evidence suggests that childhood maltreatment may also influence risk for physical illness. Findings from experimental studies in non-human primates suggest that adverse childhood experiences may influence obesity risk. However, observations from human studies showed heterogeneous results. Methods: To address these inconsistencies, we performed Medline, PsycInfo and Embase searches till August 1, 2012 for articles examining the association between childhood maltreatment and obesity. We then conducted a meta-analysis of the identified studies and explored the effects of various possible sources of bias.

CAMHS CAG Projects Day 2018

Results: A meta-analysis of 41 studies (190,285 participants) revealed that childhood maltreatment was associated with elevated risk of developing obesity over the life-course (OR=1.36, 95%CI=1.26-1.47). Results were not explained by publication bias or undue influence of individual studies. Overall, results were not significantly affected by the measures or definitions used for maltreatment or obesity, nor by confounding by childhood or adult socio-economic status, current smoking, alcohol intake, or physical activity. However, the association was not statistically significant in studies of children and adolescents, focusing on emotional neglect, or adjusting for current depression. Furthermore, the association was stronger in samples including more women and whites but was not influenced by study quality. Conclusion: Child maltreatment is a potentially modifiable risk factor for obesity. Therefore, it is important to clarify the mechanisms through which child maltreatment affects obesity risk and explore methods to remediate this effect. Subsequent studies from our team have shown that, in addition to child maltreatment, child bullying victimisation also predict obesity in adult life. These findings have now been included in a scientific statement from the American Health Association summarising the evidence linking child adversity with later cardiometabolic disease risk. Funding: Medical Research Council Publications: 1.

Suglia, SF, Koenen KC, Boynton-Jarrett R, Chan PS, Clark CJ, Danese A, Faith MS, Goldstein BI, Hayman LL, Isasi CR, Pratt CA, Slopen N, Sumner JA, Turer A, Turer CB & Zachariah JP (2018). American Heart Association Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Functional Genomics and Translational Biology; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Childhood and adolescent adversity and cardiometabolic outcomes: A scientific statement from the American Heart Association. Circulation. 137(5): e15-e28 doi: 10.1161/CIR.0000000000000536 2. Baldwin J, Arseneault L, Odgers CL, Belsky DW, Matthews T, Ambler A, Caspi A, Moffitt TE & Danese A. (2016). Childhood bullying victimization predicts overweight in young adulthood: A cohort study. Psychosomatic Medicine, 78(9): 1094-1103. doi: 10.1097/ PSY.0000000000000388 3. Takizawa R, Danese A, Maughan B & Arseneault L. (2015). Bullying victimization in childhood predicts inflammation and obesity at mid-life: A five-decade birth cohort study. Psychological Medicine. 45(13): 2705-15. doi: 10.1017/S0033291715000653 4. Danese A, Dove R, Belsky D, Henchy J, Williams B, Ambler A & Arseneault L. (2014). Leptin deficiency in maltreated children. Translational Psychiatry, 4:e446. doi: 10.1038/ tp.2014.79 5. Danese A & Tan M. (2014). Childhood maltreatment and obesity: Systematic review and meta-analysis. Molecular Psychiatry, 19(5): 544-54. doi: 10.1038/mp.2013.54

Child maltreatment and inflammation

Emotional and Behavioural Disorders

Lay Summary: Childhood maltreatment is a key risk factor for psychopathology. However, little is known about how exposure to childhood maltreatment is translated into biological risk for psychopathology. Observational human studies and experimental animal models suggest that childhood exposure to stress can trigger an enduring immune response not unlike the bodily response to physical injury, or inflammation. In turn, inflammation can affect brain development, key behavioural domains (e.g., cognition, reward or threat processing), reactivity to subsequent stressors, and, ultimately, risk for psychopathology. Further research is needed to better characterise the inflammatory links between childhood maltreatment and psychopathology, in order to prevent and treat psychopathology emerging after childhood maltreatment. State of Progress: Ongoing Abstract: Background: Childhood maltreatment is associated with high risk of mental illness, including major depression and bipolar disorder. However, it is unclear how exposure to childhood adverse psychosocial experiences can be translated into biological risk for psychopathology. Because affective disorders are increasingly linked to dysregulated immune system, we tested the association between childhood maltreatment and inflammation in the general population and within groups of individuals with affective disorders in order to explore potential immune mediation pathways. Methods: The association between childhood maltreatment and inflammation in the general population and within groups of individuals with affective disorders was measured among participants of two cohorts: The New Zealand Dunedin Multidisciplinary Health and Development Study a cohort of 1,000 children born in 1972â&#x20AC;&#x201C;73, and the UK Environmental-Risk (E-Risk) Longitudinal Twin Study, a cohort of 2,200 twins born in 1994â&#x20AC;&#x201C;95. Results: In the Dunedin Study, maltreated children had elevated inflammation levels at age 32 years, independent of key confounding factors. Although depressed individuals with a history of maltreatment had elevated inflammation levels, depressed individuals with no maltreatment history had inflammation levels similar to controls. These findings were replicated in the E-Risk Study among 12-year-old children Conclusion: Childhood maltreatment is associated with elevated inflammation levels in adult life, both in the general population and within groups of individuals with affective disorders. In turn, inflammation has been associated with the recurrence and progression of affective disorders and with resistance to conventional treatment for these conditions. These epidemiological findings have implications for understanding the clinical sequelae of childhood maltreatment including incidence, unfavourable course of illness, and poor treatment response in affective disorders. They can also point to innovative treatment strategies. Funding: Wellcome Trust, Medical Research Council, Economic and Social Research Council Publications: 1.

Baldwin JR, Arseneault L, Caspi A, Fisher, HL, Moffitt, TE, Odgers CL, Pariante C, Ambler A, Dove R, Kepa A, Matthews T, Menard A, Sugden K, Williams B &

CAMHS CAG Projects Day 2018

Danese A. (2017). Childhood victimization and inflammation in young adulthood: A genetically sensitive cohort study. Brain, Behavior, and Immunity. 67: 211-217 doi: 10.1016/j. bbi.2017.08.025 2. Danese A & Lewis S. (2017). Psychoneuroimmunology of early life stress: The hidden wounds of childhood trauma? Neuropsychopharmacology. 42(1): 99-114 doi: 10.1038/ npp.2016.198 3. Danese A & Baldwin J. (2017). Hidden wounds? Inflammatory links between childhood trauma and psychopathology. Annual Review of Psychology. 68: 517-544 doi: 10.1146/ annurev-psych-010416-044208 4. Takizawa R, Danese A, Maughan B & Arseneault L. (2015). Bullying victimization in childhood predicts inflammation and obesity at mid-life: a five-decade birth cohort study. Psychological Medicine. 45(13): 2705-15. doi: 10.1017/S0033291715000653 5. Danese A, Caspi A, Williams B, Ambler A, Sugden K, Mika J, Werts H, Freeman J, Pariante, CM, Moffitt TE & Arseneault L. (2011). Biological embedding of stress through inflammation processes in childhood. Molecular Psychiatry. 16(3): 244-6. doi:10.1038/ mp.2010.5 6. Danese A, Pariante CM, Caspi A, Taylor A & Poulton R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences of the United States of America, 104(4): 1319-24. doi: 10.1073/ pnas.0610362104 Figure 8. The association of childhood maltreatment with biomarkers of inflammation.

Abbreviations. hsCRP = high-senstivity C-reactive protein and WBC = white blood cells, indices of adult inflammation.

Emotional and Behavioural Disorders

Psychological consequences of child trafficking: A historical cohort study of trafficked children in contact with secondary mental health services

Investigators: Dr Livia Ottisova1,2, Prof Patrick Smith3, Hitesh Shetty4, Dr Daniel Stahl5, Dr Johnny Downs4,6 & Dr Sian Oram4 1 Camden Psychological Therapies Service, Camden and Islington NHS Foundation Trust; 2 Centre for Global Mental Health, KCL; 3 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, South London & Maudsley NHS Foundation Trust; 4 NIHR Maudsley Biomedical Research Centre, London, South London and Maudsley NHS Foundation Trust; 5 Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 6 Department of Child & Adolescent Psychiatry, IoPPN, KCL.

Lay Summary: Child trafficking is a significant public health problem and human rights violation affecting millions of children worldwide. Research on the mental health of trafficked children is limited. This project used data obtained from the NIHR Biomedical Research Centre Clinical Record Interactive Search (CRIS) to investigate the mental health and service use characteristics of trafficked children in contact with mental health services in England. State of Progress: Completed Abstract: Background: Child trafficking is the recruitment and movement of people aged younger than 18 for the purposes of exploitation. Research on the mental health of trafficked children is limited, and little is known about the use of mental health services by this group. This study aimed to investigate the mental health and service use characteristics of trafficked children in contact with mental health services in England. Method & Results The study employed an historical cohort design. Electronic health records of over 250,000 patients were searched to identify trafficked children, and a matched cohort of non-trafficked children was randomly selected. Data were extracted on the socio-demographic and clinical characteristics, abuse history, and trafficking experiences of the trafficked children. Logistic and linear random effects regression models were fitted to compare trafficked and non-trafficked children on their clinical profiles and service use characteristics. Fifty-one trafficked children were identified, 78% were female. The most commonly recorded diagnoses for trafficked children were post-traumatic stress disorder (PTSD) (22%) and affective disorders (22%). Records documented a high prevalence of physical violence (53%) and sexual violence (49%) among trafficked children. Trafficked children had significantly longer duration of contact with mental health services compared to non-trafficked controls (b = 1.66, 95% CI 1.09â&#x20AC;&#x201C;2.55, p<.02). No significant differences were found, however, with regards to pathways into care, prevalence of compulsory psychiatric admission, length of inpatient stays, or changes in global functioning. Conclusion: Child trafficking is associated with high levels of physical and sexual abuse and longer duration of contact with mental health services. Research is needed on most effective interventions to promote recovery for this vulnerable group.

CAMHS CAG Projects Day 2018

Funding: This project was completed in part fulfilment of a Doctorate in Clinical Psychology Publications:

Ottisova, L, Smith P, Shetty H, Stahl D, Downs J & Oram S. (2018). Psychological consequences of child trafficking: A historical cohort study of trafficked children in contact with secondary mental health services. PLoS ONE, 13, 3, e0192321

A pilot randomised controlled trial of cognitive behavioural therapy for adolescents with body dysmorphic disorder

Investigators: Prof David Mataix-Cols1,2,3, Dr Benedetta Monzani4, Dr Laura Bowyer3, Prof David Veale5,6 & Dr Georgina Krebs4,7 1 Centre for Psychiatry Research, Karolinska Instituet, Sweden; 2 Department of Psychosis studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 3 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 5 Department of Psychology, IoPPN, KCL; 6 Centre for Anxiety Disorders & Trauma, South London and Maudsley NHS Foundation Trust; 7 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL;

Lay Summary: Body dysmorphic disorder (BDD) typically starts in adolescence, but evidence-based treatments are yet to be developed and formally evaluated in this age group. This study designed and tested a package of Cognitive Behavioural Therapy (CBT) for BDD in young people aged 12-18 years old. CBT was compared to a waitlist control treatment where young people and families were called once a week to go over psycho-education materials and their symptoms were monitored. CBT was significantly better than the waitlist control condition. 40% of the CBT group and 7% of the waitlist group responded to treatment. Families and young people gave feedback on the treatment and said they found it highly acceptable. This study shows CBT for BDD has promise. State of Progress: Completed Abstract: Background: Body dysmorphic disorder (BDD) typically starts in adolescence, but evidence-based treatments are yet to be developed and formally evaluated in this age group. We designed an age-appropriate cognitive-behavioural therapy (CBT) protocol for adolescents with BDD and evaluated its acceptability and efficacy in a pilot randomised controlled trial. Methods: Thirty adolescents aged 12-18 (mean=16.0, SD=1.7) with a primary diagnosis of BDD and their families were randomly assigned to 14 sessions of CBT delivered over four months or a control condition of equivalent duration, consisting of written psycho-education materials and weekly telephone monitoring. Blind evaluators assessed participants at baseline, mid-treatment, post-treatment, and at two-month follow-up. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale Modified for BDD, adolescent version (mean baseline score=37.13, SD=4.98; range=24â&#x20AC;&#x201C;43).

Emotional and Behavioural Disorders

Results: The CBT group showed a significantly greater improvement than the control group, both at posttreatment (time×group interaction coefficient [95%CI]=-11.26 [-17.22 to -5.31]; p<.001) and at two-month follow-up (time×group interaction coefficient [95%CI]=-9.62 [-15.74 to -3.51]; p=.002). Six (40%) participants in the CBT group and one (6.7%) in the control condition were classified as responders at both time points (ᵪ 2 =4.658,p=.031). Improvements were also seen on secondary measures, including insight, depression, and quality of life at post-treatment. Both patients and their families deemed the treatment as highly acceptable. Conclusion: Developmentally tailored CBT is a promising intervention for young people with BDD, though there is significant room for improvement. Further clinical trials incorporating lessons learned in this pilot and comparing CBT and pharmacological therapies, as well as their combination, are warranted. Funding: National Institute for Health Research (NIHR) Mental Health Publication:

Mataix-Cols D, de la Cruz LF, Isomura K, Anson M, Turner C, Monzani B, ... & Krebs G. (2015). A pilot randomized controlled trial of cognitive-behavioral therapy for adolescents with body dysmorphic disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 54(11): 895-904.

Ritualised eating in young people with obsessive compulsive disorder: Clinical characteristics and treatment outcomes

Investigators: Dr Amita Jassi1,2, Natasha Patel1, Dr Katie Lang3, Dr Isobel Heyman4,5 & Dr Georgina Krebs1,6 1 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 2 Department of Psychosis studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Section of Eating Disorders, Department of Psychological Medicine, IoPPN, KCL; 4 Great Ormond Street Hospital, London; 5 Institute of Child Health, University College London; 6 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL.

Lay Summary: Obsessive-compulsive disorder (OCD) encompasses a wide range of symptoms and ritualised eating is one type of symptom. However, we are not sure on how common this is in young people with OCD. This study looked at how many young people with OCD reported this type of symptom. Out of a group of 396 young people, 101 (25%) reported OCD makes them eat in a particular way. For a small group of young people (n=10), this led to them being underweight. We compared how well they responded to treatment (Cognitive Behaviour Therapy) compared to matched young people with healthy weight (n=10). Results showed they did significantly worse, indicating that when treatment is completed with underweight young people, it is not effective. The study concluded that health and weight should be restored before starting CBT for OCD to make sure it has the best chance of success. State of Progress: Completed

CAMHS CAG Projects Day 2018

Abstract: Background: Ritualised eating can present as a symptom of Obsessive Compulsive Disorder (OCD) and in some extreme cases can lead to restricted eating causing low-weight. Little is known about the prevalence and clinical significance of ritualised eating in paediatric OCD populations. Methods: Participants were 397 patients referred to a specialist OCD clinic. The prevalence, demographic and clinical characteristics as well as treatment outcomes were compared for young people who endorsed ritualised eating on a structured measure (n=101) and those who did not (n=296). Results: Ritualised eating was common with 25% exhibiting this symptom. There were no significant differences in demographic or treatment outcomes between those who did and did not have ritualised eating symptom. However, ritualised eaters had more severe OCD and greater functional impairment. Cognitive Behavioural Therapy (CBT) outcomes for an under-weight sub-group (n=10) were compared to a matched healthy weight group (n=10). CBT outcomes were significantly worse in the underweight group. Conclusion: CBT for OCD is not effective. Therefore, physical health should be prioritised and weight should be restored before starting CBT for OCD to make sure it has best chance of success. Funding: N/A Publication:

Jassi AD, Patel N, Lang K, Heyman I & Krebs G. (2016). Ritualised eating in young people with obsessive compulsive disorder; clinical characteristics and treatment outcomes. Journal of Obsessive-Compulsive and Related Disorders, 8, 1-8. Figure 9. Mean CYBOCS total scores at baseline and post-treatment for the low versus the healthy weight group.

Abbreviation. CYBOCS = Childrenâ&#x20AC;&#x2122;s Yale-Brown Obsessive-Compulsive Scale. Error bars represent standard errors. 80

Emotional and Behavioural Disorders

Obsessive-compulsive disorder multi-cultural youth project

Investigators: Dr Amita Jassi1,2, Dr Gazal Jones1,2 & Kike Thomas-Smith1,2 1 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 2 Department of Psychosis studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: This project aims to address the inequality in access to services for OCD, for young people and their families across ethnic groups. From studies we have completed, ethnic minorities are significantly under-represented in mental health services and this is particularly the case for OCD. We also know that those who do access services respond equally well to evidence-based treatments for OCD. Therefore, the main issue is not the treatment that is offered, but rather the issue of accessing services in the first place. Several barriers to accessing services have been identified by undertaking surveys and interviews with ethnic minority groups. We plan to address these barriers with two groups of interventions. (1) Intervention 1: Disseminate information on OCD in a variety of ways; (2) Intervention 2: Trial a model of service delivery in the heart of the community where ethnic minorities go for support. We have several methods planned to evaluate if these interventions have been successful in overcoming the identified barriers. Ultimately, these will measure whether there is an increase in the number of ethnic minorities accessing mental health services for OCD. Several methods of disseminating results of the project are planned in order to maximise the benefits of the project. One aim of this project is to trial various strategies and to evaluate their effectiveness, so that successful strategies can be shared and undertaken by other services. State of Progress: Ongoing Abstract: Background: Obsessive Compulsive Disorder (OCD) is characterised by repetitive, unwanted behaviours and intrusive recurrent thoughts. OCD is ranked in the top 10 most debilitating illnesses in the world (WHO, 2002). OCD is common in young people and by late adolescence the lifetime prevalence of OCD is 2-3% (Zohar, 1999). If untreated, OCD can be a chronic and debilitating condition which is likely to persist into adulthood and represent a substantial burden for the sufferers, their families and society in general (Skoog & Skoog, 1999). Ethnic minorities are significantly under-represented in OCD services in particular, and observations in our clinic indicate that ethnic minority groups do not access the service as much as other groups (de la Cruz et al., 2015a). Two studies (FernĂĄndez de la Cruz et al., 2016; Kolvenbach et al., 2016) were carried out to understand what the barriers to accessing services were. They highlighted the following 4 themes of barriers to utilising services for OCD, identified by ethnic minority groups: (1) Theme 1: Inaccurate perceptions and lack of knowledge on OCD and child mental health services; (2) Theme 2: Stigma and fear of discrimination/judgment; (3) Theme 3: Inaccessibility; (4) Theme 4: Lack of integration with community and religious groups. The small number of ethnic minority youth who do gain access do just as well in treatment (FernĂĄndez de la Cruz et al., 2015b). This project aims to address and overcome the barriers identified to increase access to OCD services and effective treatment. There is a significant need for this project; we know early detection and intervention for OCD is crucial to prevent chronicity and further personal and financial consequences for the sufferers, their families and society at large (Micali et al., 2010). Therefore, it is vital that we address the unmet needs of ethnic minority groups. 81

CAMHS CAG Projects Day 2018

Methods: Providing community interventions that increase knowledge and provide information for these groups as well as making the service accessible by overcoming identified barriers. This will include teaching and training of staff within schools and community settings such as youth clubs. We will also set up information stalls within the community (e.g., local libraries, colleges, GPs youth events) where we will speak to members of the community about OCD and offer screening assessments for OCD. We will also be setting up webinars about OCD and mental health. Results: We have now gathered some initial data and will be analysing this data for trends. Conclusion: We would expect the main outcome for the project will be increased use of mental health services for OCD sufferers and their families who come from ethnic minority groups. We also hope by linking in with community groups and increasing their understanding of these difficulties, this will increase the support network around these families in settings they access more readily. Ultimately this project is aimed at improving the experience of care for ethnic minority youth provided by our SLaM services. We have clearly identified issues that need to be addressed to make our services are more user friendly and to meet the needs of ethnic minority groups, so we hope this project will lead to better experiences for them Funding: Maudsley Charity Publications: 1.

Fernández de la Cruz LF, Llorens M, Jassi A, Krebs G, Vidal-Ribas P, Radua J, ... & Mataix-Cols D. (2015a). Ethnic inequalities in the use of secondary and tertiary mental health services among patients with obsessive–compulsive disorder. The British Journal of Psychiatry, 207(6):530-535. 2. Fernández de la Cruz LF, Jassi A, Krebs G, Clark B, & Mataix-Cols D. (2015b). Phenomenology and treatment outcomes in children and adolescents from ethnic minorities with obsessive–compulsive disorder. Journal of Obsessive-Compulsive and Related Disorders, 4:30-36. 3. Fernández de la Cruz LF, Kolvenbach S, Vidal-Ribas P, Jassi A, Llorens M, Patel N, ... & Mataix-Cols, D. (2016). Illness perception, help-seeking attitudes, and knowledge related to obsessive–compulsive disorder across different ethnic groups: a community survey. Social Psychiatry and Psychiatric Epidemiology, 51(3):455-464. 4. Kolvenbach S, Fernández de la Cruz LF, Mataix-Cols D, Patel N & Jassi A. (2018). Perceived treatment barriers and experiences in the use of services for obsessive– compulsive disorder across different ethnic groups: a thematic analysis. Child and Adolescent Mental Health, 23(2):99-106.

How resistant is “treatment resistant” obsessive compulsive disorder in youth?

Investigators: Dr Georgina Krebs1,2, Dr Amita Jassi1,3, Dr Isobel Heyman4,5 & Prof David Mataix-Cols1, 6,7 1 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 2 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Department of Psychosis studies, IoPPN, KCL; 4 Great Ormond Street Hospital, London; 5 Institute of Child Health, University College London; 6 Centre for Psychiatry Research, Karolinska Instituet, Sweden; 7 Department of Psychosis studies, IoPPN, KCL. 82

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Lay Summary: Obsessive-compulsive disorder (OCD) is perceived as difficult to treat and often clinicians’ trial evidence-based treatment (Cognitive Behavioural Therapy and medication) and young people do not respond. These young people’s OCD is then regarded as ‘treatment resistant’. Forty-three young people with severe, treatment-resistant OCD were treated in the national and specialist OCD clinic using protocolised CBT and medication. Even though they were regarded as ‘treatment resistant’, 58% responded to treatment and 22% remitted from their OCD. 15 young people who responded to treatment were interviewed about their previous treatment where their OCD was considered ‘treatment resistant’. 95.5% of their previous treatment was considered inadequate, using a predetermined criterion. The most common inadequacy was insufficient focus on exposure techniques. State of Progress: Completed Abstract: Background: Obsessive-compulsive disorder (OCD) is often perceived as being difficult to treat. This study aimed to test the hypothesis that treatment non-response in routine clinical practice is often due to failures in the delivery of treatment, and that most patients who are apparently treatment-resistant will respond to treatment if adequately delivered. Methods: Forty-three young people with severe, treatment-resistant OCD (defined as Children’s Yale-Brown Obsessive-Compulsive Scale [CY-BOCS] scores ≥30 and non-response to previous cognitive behaviour therapy [CBT] and selective serotonin reuptake inhibitors) were referred to a specialist clinic and completed a course of manualised CBT, with (N = 21) or without (N = 22) optimisation of medication. A sub-sample (N = 15) completed a semi-structured interview to determine characteristics of their previous CBT; quality was assessed according to pre-determined criteria. Results: Specialist treatment was associated with significant reductions in OCD symptoms at post-treatment with gains maintained at 3-month follow-up. At the 3-month follow-up, 58% of patients showed a meaningful clinical response (≥35% drop on the CY-BOCS) and 22% were in remission (≤12 on the CYBOCS). Patients whose medication was optimised tended (non-significantly) to have better responses. The quality of previous CBT was assessed in a sub-group of participants and rated as inadequate in 95.5% of cases. The most common inadequacy was insufficient focus on exposure techniques. Conclusion: These findings provide support for the notion that treatment non-response in routine practice may be due to technical treatment failures and highlight the need to disseminate good quality evidence-based treatment among this population. Research is also needed to understand factors that impede outcome to further improve response and remission rates. Funding: At the time, Dr Georgina Krebs received salary support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Publication:

Krebs G, Isomura K, Lang K, Jassi A, Heyman I, Diamond H, ... & Mataix-Cols D. (2015). How resistant is ‘treatment-resistant’ obsessive-compulsive disorder in youth? British Journal of Clinical Psychology, 54(1), 63-75.

CAMHS CAG Projects Day 2018

A pilot study of internet-delivered cognitive behavioural therapy for adolescents with obsessive-compulsive disorder

Investigators: Dr Amita Jassi1,2, Dr Georgina Krebs1,3 & Dr Bruce Clark1 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 2 Department of Psychosis studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Social, Genetic and Developmental Psychiatry Centre, IoPPN, KCL. 1

Lay Summary: The overall goal of our research is to develop a new format of effective treatment for paediatric obsessive-compulsive disorder (OCD). This is a preliminary investigation into the effectiveness, acceptability and feasibility of Internet-delivered Cognitive Behaviour Therapy (ICBT) for a clinical sample of young people with OCD. ICBT could have the potential to increase access to and the availability of treatment of OCD in adolescents by overcoming geographical barriers and shortages in trained therapists. This would be desirable not only for patients and their families, but also for services, who could decrease their waiting times and maximise clinician efficiency given that internet-delivered interventions may be more cost-effective than traditional formats of CBT. State of Progress: Ongoing Abstract: Background: Cognitive-behavioural therapy (CBT) is the first-line treatment for young people with obsessivecompulsive disorder (OCD), but most patients do not have access to this treatment. Thus, innovative ways to increase the accessibility of CBT are needed. The objective of this study was to evaluate the efficacy, feasibility and acceptability of therapist-guided internet-based CBT (ICBT) for adolescents with OCD. Methods: Fifteen young people with OCD completed a course of ICBT (12 sessions) and parents complete five parallel sessions. Young people were required to log onto the online treatment 2-3 times a week and complete sessions which are parallel to sessions in clinic face-to-face treatment. Therapists also logged onto the system 2-3 times a week to check in and message to support families through the treatment. Measure of OCD, mood and overall functioning were taken at the beginning, end, 3 and 6-month follow-up points. Feedback on the treatment package was taken at the end of treatment. Results: Pending Conclusion: Pending Funding: Maudsley Charity Publications:

This paper is currently being written with our collaborators at the Karolinska Institute. Lenhard F, Andersson E, Mataix-Cols D, Rück C, Vigerland S, Högström J, ... & Serlachius E. (2017). Therapist-guided, internet-delivered cognitive-behavioral therapy

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for adolescents with obsessive-compulsive disorder: A randomized controlled trial. Journal of the American Academy of Child & Adolescent Psychiatry, 56(1): 10-19.

Long-term outcomes of cognitive behavioural therapy for adolescent body dysmorphic disorder

Investigators: Dr Georgina Krebs1,2, Dr Lorena Fernandez De La Cruz3, Dr Benedetta Monzani4, Dr Laura Bowyer1, Dr Martin Anson1,5, Dr Jacinda Cadman6, Dr Isobel Heyman2, Dr Cynthia Turner7, Prof David Veale7,8 & Prof David Mataix-Cols3,4 1 National & Specialist OCD, BDD and Related Disorders Clinic, South London and Maudsley NHS Foundation Trust; 2 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 3 Centre for Psychiatry Research, Karolinska Instituet, Sweden; 4 Department of Psychosis studies, IoPPN, KCL; 5 School of Psychology, Politics and Sociology, Canterbury Christ Church University; 6 Griffith University, Gold Coast, Australia; 7 University of Queensland, Brisbane, Australia; 8 Department of Psychological Medicine, IoPPN, KCL.

Lay Summary: The aim of the study was to evaluate the long-term durability of individual cognitive behavioural therapy (CBT) for adolescent body dysmorphic disorder (BDD). The study involved 26 participants who had received CBT and were assessed 2-, 6-, and 12-months following CBT treatment. Analyses indicated that gains were maintained over a 12-months follow-up period, with 50% of participants classifying as responders and 23% as remitters. Results suggest that CBT for adolescent BDD provides long-term reduction in BDD symptoms. However, given remaining symptoms and risk, longer-term monitoring is advised in this population. Future research is needed to focus on enhancing the efficacy of CBT to improve long-term prognosis. State of Progress: Completed Abstract: Background: Emerging evidence suggests that cognitive-behavioural therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomised controlled trial of CBT for BDD to determine whether treatment gains were maintained. Methods: Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, mid-treatment, post-treatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. Results: BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month followup. Neither baseline insight nor baseline depression predicted long-term outcomes. 85

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Conclusion: The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Funding: This research was funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0110-21231). David Veale acknowledges salary support from the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. Georgina Krebs is funded by an MRC Clinical Research Training Fellowship (MR/N001400/1). Publication:

Krebs G, De La Cruz LF, Monzani B, Bowyer L, Anson M, Cadman J, Heyman I, Turner C, Veale D & Mataix-Cols D. (2017). Long-term outcomes of cognitivebehavioral therapy for adolescent body dysmorphic disorder. Behavior Therapy, 48(4): 462473. doi: 10.1016/j.beth.2017.01.001. Figure 10. Long-term outcomes of cognitive behaviour therapy for adolescent body dysmorphic disorder.

Abbreviations. BDD-YBOCS-A = Yale Brown obsessive-compulsive scale, modified for adolescent with body dysmorphic disorder; 2m FU = 2-month follow-up; 6m FU = 6-month follow-up, 12m FU = 12-month follow-up. Error bars indicate 95% confidence intervals.

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Longitudinal assessment of manic symptoms (LAMS)

Investigators: Ilyas Sagar-Ouriaghli1, Dr Gordana Milavic3, Rebecca Barton3, Natalie Heaney1, Dr Federico Fiori1,2, Dr Kate Lievesley1, Dr Jatinder Singh1 & Prof Paramala Santosh1,2 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD) Research Team, South London and Maudsley NHS Foundation Trust; 3 South London and Maudsley NHS Foundation Trust.

Lay Summary: This multi-site study was used to compare Disruptive Mood Dysregulation Disorder (DMDD) and Mixed Disorder of Emotion and Conduct (MDEC) diagnoses in order to understand them and cooccurring conditions. State of Progress: Completed Abstract: Background: The aim of the study was to determine whether Disruptive Mood Dysregulation Disorder (DMDD) is a unique entity within the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) and to compare it with possible equivalent disorders in other classificatory systems. Methods: This study looked at the United Kingdom arm (UK-LAMS) of the US National Institute of Mental Health (NIMH) Longitudinal Assessment of Manic Symptoms (LAMS) that followed a group of children aged 6–12 years old with elevated symptoms of mania (ESM+) and then compared them with a group of children without ESM (ESM−). Results: In this study, 47 individuals met the criteria for DMDD and 45 met the criteria for MDEC. None of those who fulfil DMDD or MDEC criteria have a sole diagnosis of ODD or CD. Moreover, 24 (35.29%) patients were identified as fulfilling both DMDD and MDEC criteria. Considering these points highlighted above, further investigation of the data sought to highlight the overlap of the DMDD and MDEC with other diagnostic labels. Conclusion: This study focused on the obfuscation surrounding irritability and aggression in young children. We found that although DMDD has its limitations, it is still a unique entity from MDEC as defined by the ICD-10. DMDD and now MDEC both appeared to capture individuals who fulfilled the diagnostic criteria for ODD/CD, ADHD and/or an anxiety disorder, all of which needs to be considered when managing them. This study suggests that both DMDD and MDEC may be better viewed as specifiers. Funding: Maudsley Hospital Charity, London, UK, who provided the grant (Grant no: 626) Publication:

Sagar-Ouriaghli I, Milavic G, Barton R, Heaney N, Fiori F, Lievesley K, Singh J & Santosh P. (2018). Comparing the DSM-5 construct of disruptive mood dysregulation disorder and ICD-10 mixed disorder of emotion and conduct in the UK Longitudinal Assessment of Manic Symptoms (UK LAMS) Study. European Children &Adolescent Psychiatry. 87

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Suicidality: Treatment occurring in paediatrics (STOP) – Development of a comprehensive web-based methodology for the assessment and monitoring of suicidality and its mediators in children and adolescents

Investigators: Dr Kate Lievesley1, Dr Regina Sala1, Dr Nantia Iakovidou1, Dr Federico Fiori1,2, Dr Jatinder Singh1, Prof Paramala Santosh1,2 & the STOP consortium. 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust.

Lay Summary: The overarching goal of the “Suicidality: Treatment Occurring in Paediatrics” (STOP) project was to develop a comprehensive web-based methodology for the assessment and monitoring of suicidality and its mediators in children and adolescents using the HealthTrackerTM (www.healthtracker.co.uk) platform with a view to develop a suicidality assessment and monitoring module, a biopsychosocial mediators of suicidality assessment module, and a suicidality-related psychiatric and physical illness module. State of Progress: Completed Abstract: Background: Suicide is one of the major causes of death worldwide, with figures suggesting that approximately one million people commit suicide each year. Suicide risk follows a multifactorial trajectory and is increased in many psychiatric disorders varying by diagnosis, gender and age. Literature evidence suggests that some risk factors for suicide might be different in children and adolescents compared with adults. The child and adolescent population represents a particularly vulnerable group and there is a need for the development of instruments aimed at specifically assessing protective and risk factors in young people. Methods: The STOP Suite of Suicidality Measures developed on the HealthTrackerTM (www.healthtracker. co.uk) platform consisted of the HealthTrackerTM based STOP Suicidality Assessment Scale (SAS) alongside other scales. The scales were validated in seven cohorts as part of three observational trials. The HealthTrackerTM platform allowed the scales to be used by children, adolescents, parents, teachers as well as clinicians. HealthTrackerTM is ideal for post-marketing surveillance of medication as it can capture longitudinal data about behaviour, emotions, side-effects, cognitive functions, quality of life of both child and family along with details of all medication used as well as compliance. Results: The information gained from the scales in the HealthTrackerTM based STOP Suite of Suicidality Measures allowed predictive modelling to be performed to identify specific items for suicidality leading to the predictors of suicidality in children to be developed into a single scale. Conclusion: The STOP project provided a comprehensive evaluation of suicidality monitoring in children and adolescents aged between 8-18 years. The HealthTrackerTM based STOP Suite of Suicidality Measures developed on the HealthTrackerTM platform was validated during the course of the project in seven cohorts as part of three observational trials and shown that it can be used to gather 88

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comprehensive information on both psychopathology and medication-related suicidality. Funding: This research was funded by the European Community’s Seventh Framework Programme (FP7/20072013) under grant agreement no. 261411 and the BRC for exploring sensor based technology and the development of clinical decision making analytics. Publication:

Flamarique I, Santosh P, Zuddas A et al. (2016). Development and psychometric properties of the Suicidality: Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents. BMC Pediatrics. 16, 213.

Feasibility randomised controlled trial of the (“DISCOVER”) workshop programme for 15-18 year olds with anxiety and/or depression in clinic settings

Investigators: Dr Christina Loucas1, Dr Irene Sclare1, Dr Daniel Stahl2 & Dr Daniel Michelson1 1 Child and Adolescent Mental Health Services Clinical Academic Group, South London and Maudsley NHS Foundation Trust; 2 Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: This project tested the DISCOVER model for referred adolescents with anxiety and depression, when delivered in CAMHS clinics by the DISCOVER team. State of Progress: Completed in 2017 Abstract: “DISCOVER” one-day CBT workshops have been developed to provide accessible, developmentallysensitive and evidence-based psychological support for older adolescents experiencing emotional difficulties. Previous school-based evaluations have shown positive outcomes. The current study aimed to test the model for referred adolescents in CAMHS. A feasibility randomised controlled trial assessed feasibility, acceptability and preliminary outcomes of the DISCOVER intervention when delivered to 15-18-year-olds with emotional difficulties recruited from CAMHS waiting lists, in comparison with usual care. Research feasibility parameters were also collected to inform a full-scale effectiveness trial of DISCOVER. Methods: Feasibility indicators included rates of recruitment, randomisation, intervention participation (group workshops and individualised follow-up telephone calls), and data collection (at baseline and 8-week follow-up). Intervention acceptability was assessed using a structured service satisfaction questionnaire and semi-structured qualitative interviews with intervention participants. Preliminary clinical outcomes were explored using adolescent-reported validated measures of anxiety, depression and well-being. 89

CAMHS CAG Projects Day 2018

Results: N=24 participants were randomised to intervention and usual care groups. Workshop attendance was good and high levels of treatment satisfaction were reported, although feasibility challenges emerged in recruitment and randomisation. Small-to-medium non-significant effects were found for anxiety and well-being, and negligible effects for depression; interpretability was limited due to the small sample size. Conclusion: DISCOVER appears to be a feasible and acceptable intervention model when delivered in the clinic setting for 15-18-year-olds with emotional difficulties, who have been recruited from CAMHS waiting lists. A full-scale RCT is warranted to evaluate effectiveness; protocol modifications may be necessary to ensure feasible recruitment and randomisation procedures. Funding: This project was undertaken in part fulfilment of Dr Loucas’ doctoral requirements. DISCOVER staffing costs were supported by a grant from Guy’s and St Thomas’. Publication: Manuscript to be submitted to Psychology and Psychotherapy: Theory, Research and Practice

Mindfulness-based cognitive therapy for depression in adolescents

Investigators: Dr Catherine Ames1,2, Jessica Richardson1, Suzanna Payne3, Eleanor Leigh1,2 & Dr Patrick Smith1,2 1 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Bethlem Adolescent Unit, South London and Maudsley NHS Foundation Trust.

Lay Summary: Mindfulness-Based Cognitive Therapy (MBCT) has been shown to help adults with depression to stay well. Mindfulness approaches have not been rigorously in adolescents with depression. This project tested whether a Mindfulness course was acceptable to adolescents, and feasible to deliver in CAMHS. Results were promising. State of Progress: Completed Abstract: Background: Mindfulness-Based Cognitive Therapy (MBCT) has been shown to be effective in preventing relapse of depression in adults, but has not previously been applied to adolescents who have residual symptoms of depression following treatment Methods: An 8-week MBCT group was adapted for adolescents and evaluated using qualitative and quantitative measures. 90

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Results: Participants report high levels of satisfaction with the group intervention. Qualitative analysis of semistructured interviews provides areas for future development of this intervention. Pilot data indicate reductions in depressive symptoms, alongside positive change in mindfulness skills, quality of life and rumination Conclusion: Preliminary evidence for the use of MBCT with this group of adolescents is provided. Funding: This project was completed in part fulfilment of a Doctorate in Clinical Psychology Publication:

Ames CS, Richardson J, Payne S, Smith P & Leigh E. (2014). Mindfulness-based cognitive therapy for depression in adolescents. Child and Adolescent Mental Health, 19(1):74-78.

Trauma-focused cognitive behaviour therapy posttraumatic stress disorder (PTSD) in young children aged 3 to 8 years

Investigators: Dr Tim Dalgleish1,2, Peter Watson1, Dr Nicola Morant3, Dr Richard Meiser-Stedman4, Dr Ayla Humphrey2, Dr Anna McKinnon1 & Dr Patrick Smith5,6 1 MRC Cognition and Brain Sciences Unit, Cambridge; 2 Cambridgeshire and Peterborough NHS Foundation Trust; 3 Department of Psychology, University of Cambridge; 4 Department of Clinical Psychology, University of East Anglia; 5 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 6 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: Young children who are exposed to traumatic events may develop post-traumatic stress disorder (PTSD). Relatively little research has been carried out with this age group. In a series of studies, we aim to develop our understanding of young children’s responses to trauma exposure, and to develop and evaluate a theory-driven talking therapy, Trauma-Focused CBT for young children. State of Progress: Ongoing Abstract: Background: Following horrific or life-threatening events approximately 10 to 15% of young children develop post-traumatic stress disorder (PTSD). The symptoms of this disorder are distressing - nightmares, flashbacks, anger outbursts and disturbed play. These symptoms cause major disruption to a child’s functioning and, if left untreated, can persist for many years. As yet, there are no established empirically-validated treatments for PTSD in young children. Trauma-focused cognitive behaviour therapy (TF-CBT) is a psychological intervention that is effective in treating the disorder in older children (8 to 12 years), adolescents and adults. This study examines TF-CBT adapted for children aged between 3 and 8 years.

CAMHS CAG Projects Day 2018

Methods: This protocol describes a two-arm exploratory randomised controlled trial comparing TF-CBT to treatment as usual (TAU) in children aged 3 to 8 years with a principal diagnosis of PTSD following a single-event discrete trauma. Using a half-crossover design, 44 participants will be randomly allocated to receive the intervention or to receive TAU. Those allocated to TAU will be offered TF-CBT at the end of the “treatment” period (approximately 12 weeks) if still indicated. The primary outcome is PTSD diagnosis according to DSM-5 criteria for children 6 years and younger at post-treatment. Secondary outcomes include effects on co-morbid diagnoses and changes in emotion and trauma symptoms at each of the follow-up points (post-treatment, 3-months, 12-months). Additionally, broader efficacy will be considered with regard to treatment feasibility, acceptability and service utilisation. The key targets of the intervention are trauma memory, the interpretation of the meaning of the event, and the management of symptoms. Conclusion: This is the first European trial to examine the efficacy of TF-CBT in alleviating PTSD in very young children. As well as providing much-needed data on the utility of the intervention, this exploratory trial will also allow us to gather important information about the feasibility of delivering the treatment in UK National Health Service (NHS) settings, and its acceptability to the children and their families. This study will highlight aspects of the intervention that need improvement or modification in preparation for a full-scale evaluation in a larger sample Funding: National Institute for Health Research, Research for Patient Benefit Scheme Publications: 1.

Dalgleish T, Goodall B, Chadwick I, Werner-Seidler A, McKinnon A, Morant N, Schweizer S, Panesar I, Humphery A, Watson P, Lafortune L, Smith P & MeiserStedman R. (2015). Trauma-focused cognitive behaviour therapy versus treatment as usual for post-traumatic stress disorder (PTSD) in young children aged 3 to 8 years: Study protocol for a randomised controlled trial. Trials, 16(1). Goodall B, Chadwick I, McKinnon A, Werner-Seidler A, Meiser-Stedman R, Smith P & Dalgleish, T. (2017). Translating the cognitive model of PTSD to the treatment of very young children: A single case study of an 8-year-old motor vehicle accident survivor. Journal of Clinical Psychology. 73(5): 511- 523. Meiser-Stedman R, Smith P, Yule W, Glucksman E & Dalgleish T. (2017). Posttraumatic stress disorder in young children three years post-trauma: Prevalence and longitudinal predictors. The Journal of Clinical Psychiatry. 78(3):334-339.

Cognitive therapy as an early treatment for posttraumatic stress disorder in children and adolescents

Investigators: Dr Richard Meiser-Stedman1, Dr Patrick Smith2,3, Dr Anna McKinnon4, Dr Clare Dixon4, Dr David Trickey5, Prof Anke Ehlers6, Prof David M. Clark6, Dr Adrian Boyle7, Peter Watson4, Prof Ian Goodyer8 & Dr Tim Dalgleish4, 9 1 Department of Clinical Psychology, University of East Anglia; 2 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 3 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL). 4 MRC Cognition and Brain Sciences Unit, Cambridge; 5 Anna Freud National Centre for Children and Families, London; 6 Oxford Centre for Anxiety Disorders and Trauma, Department of Experimental Psychology, University of Oxford; 7 Cambridge University Hospitals NHS Foundation Trust, 92

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Cambridge; 8 Section of Developmental Psychopathology, Department of Psychiatry, University of Cambridge; 9 Cambridgeshire and Peterborough NHS Foundation Trust.

Lay Summary: Effectiveness of psychological therapy for chronic PTSD in children and adolescents is now well established. However, few studies have investigated early intervention for acute PTSD in young people. This trial tested Cognitive Therapy for acute PTSD, finding that it was clinically efficacious, and cost-effective. State of Progress: Completed Abstract: Background: Few efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). Methods: Twenty-nine youth (8–17 years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2–6 months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks. Results: Significantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04–.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safetyseeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. Conclusion: This trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of “watchful waiting” into the 2-6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required. Funding: Medical Research Council (MRC) Clinician Scientist Fellowship awarded to Dr Meiser-Stedman. Publications: 1.

Meiser-Stedman R, Smith P, McKinnon A, Dixon C, Trickey D, Ehlers A, Clark DM, Boyle A, Watson P, Goodyer I & Dalgleish T. (2017). Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents: A randomized controlled trial addressing preliminary efficacy and mechanisms of action. Journal of Child Psychology & Psychiatry, 58(5):623-633. Shearer J, Papanikolaou N, Meiser-Stedman R, McKinnon A, Dalgleish T, Smith P, Dixon C & Byford S. (2017). Cost-effectiveness of cognitive therapy as an early intervention for post-traumatic stress disorder in children and adolescents: A trial based evaluation and model. Journal of Child Psychology & Psychiatry. doi:10.1111/jcpp.12851 93

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Cognitive therapy for the treatment of posttraumatic stress disorder (PTSD) in youth exposed to multiple traumatic stressors: A phase II randomised controlled trial

Investigators: Dr Richard Meiser-Stedman1, Dr Tim Dalgleish2, Dr Patrick Smith3,4, Prof Lee Shepstone5 & Prof Sarah Byford6 1 Department of Clinical Psychology, University of East Anglia; 2 MRC Cognition and Brain Sciences Unit, Cambridge; 3 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 4 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 5 Norwich Medical School, University of East Anglia; 6 Health Service & Population Research, IoPPN, KCL.

Lay Summary: Most adolescents will be exposed to a traumatic event by the age of 18 years old, and many will be exposed to multiple traumas. The psychological consequences of exposure to multiple trauma can be broad, and may include severe forms of post-traumatic stress disorder (PTSD). Although several trials have tested the effect of therapy for young people with PTSD that has arisen after exposure to a single event, no RCTs in the UK have so far addressed the treatment of youth with PTSD that has arisen after multiple trauma exposure. This multi-site trial (including SLaM community CAMHS teams) will evaluate Cognitive Therapy for PTSD (CT-PTSD) when it is delivered by trained front-line CAMHS workers, compared to Treatment as Usual. State of Progress: Ongoing Abstract: Background: Traumatic events are experienced by up to two-thirds of children by age 16. Such experiences include single, discrete incidents (e.g. road accidents, natural disasters, assaults), as well as multiple traumatic experiences (e.g. physical or sexual abuse, witnessing domestic violence, war or community violence). The psychological, social, and physical consequences of these traumas are often profound and longlived. Many exposed children and adolescents go on to develop posttraumatic stress disorder (PTSD). PTSD is a deeply distressing and disabling psychiatric disorder comprising symptoms of trauma reexperiencing (e.g. flashbacks, nightmares), avoidance (e.g. social withdrawal, emotional numbing), and hyperarousal (e.g. anger outbursts). PTSD in youth is usually comorbid with other psychiatric conditions, markedly impairs educational, social and daily functioning and may persist for years or even decades if untreated. For those young people subjected to multiple traumatic stressors, the clinical presentation of PTSD is particularly severe. No RCTs in the UK have so far addressed the treatment of youth with PTSD that has arisen after multiple trauma exposure. Methods: Phase II RCT Results: The trial is ongoing, with recruitment on target. Funding: National Institute for Health Research (NIHR) Career Development Fellowship to Dr MeiserStedman 94

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Randomised control trial of a CBT trauma recovery program in Palestinian schools

Investigators: Prof Ian Barron1, Dr Ghassan Abdallah2 & Dr Patrick Smith3,4 1 School of Education, Social Work and Community Education, University of Dundee; 2 Centre for Applied Research in Education, Ramallah, Palestine; 3 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 4 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: The Children and War Foundation was established after the war in former Yugoslavia in the mid-1990s. Many organisations tried to mitigate the effects of the war on children, but few interventions were based on evidence and fewer were properly evaluated. The Foundation was established in Norway with the aim of promoting better evidence-based interventions to help children after wars and natural disasters. The Foundation has developed a number of empirically grounded manuals that aim to help children learn strategies that will lessen the stress reactions that they have developed. The manuals are designed to be delivered by personnel who are not necessarily very experienced in child mental health. They are aimed at groups of children using a public health approach to reach large numbers in a short space of time. The strategies are not intended as individual therapy. The Teaching Recovery Techniques manual has been used following a number of earthquakes and other natural disasters. This trial tested the program when offered to young people with post-traumatic stress disorder (PTSD) symptoms living in the West Bank, Palestine. State of Progress: Completed & Ongoing Abstract: Background: The current study aimed to assess the Teaching Recovery Techniques (TRT) trauma recovery program within the context of ongoing violence. Methods: Utilising a randomised controlled trial, 11-14-year old students in Nablus, Palestine, were allocated by class to intervention or wait-list control conditions. Standardised measures assessed trauma exposure, posttraumatic stress disorder (PTSD), grief, and depression. Program fidelity and participant experiences were measured by adherence questionnaires and focus groups. Results & Conclusion: The Teaching Recovery Techniques program has the potential to ameliorate childrenâ&#x20AC;&#x2122;s trauma symptoms during situations of ongoing violence. Funding: Children and War Foundation www.childrenandwar.org Publications: 1.

Yule W, Dyregrov A, Raundalen M & Smith P. (2013). Children and war: The work of the children and war foundation. European Journal of Psychotraumatology. 4:18424 , doi: 10.3402/ejpt.v4i0.18424 Barron I, Abdallah G & Smith P. (2012). Randomized controlled trial of a CBT trauma recovery programme in Palestinian schools. Journal of Loss and Trauma. 18(4): 306-321, doi: 10.1080/15325024.2012.688712 95

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Internet-delivered cognitive therapy (iCT) for young people with post-traumatic stress disorder (PTSD)

Investigators: Dr Patrick Smith1,2, Prof David Clark3, Prof Anke Ehlers3, Dr Tim Dalgleish4, Dr Richard Meiser-Stedman5, Prof William Yule2 & Dr Kim Goldsmith6 1 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 3 Oxford Centre for Anxiety Disorders and Trauma, Department of Experimental Psychology, University of Oxford; 4 MRC Cognition and Brain Sciences Unit, Cambridge; 5 Department of Clinical Psychology, University of East Anglia; 6 Department of Biostatistics and Health Informatics, IoPPN, KCL.

Lay Summary: Face to face Cognitive Therapy is an effective treatment for post-traumatic stress disorder (PTSD) in children and young people, but is not commonly available in the NHS. There is an urgent need to disseminate these effective treatments for PTSD in youth. In this project, we are building software for an Internet-delivered version of our effective face-to-face Cognitive Therapy for PTSD, which will be accessible online via computers, tablets, and smart-phones. Internet delivered Cognitive Therapy (iCT) for PTSD offers huge potential for very wide, cost-effective dissemination of a highly effective treatment. State of Progress: Ongoing Abstract: Background: Post-Traumatic Stress Disorder (PTSD) in youth is a common problem in the UK and globally. Most young people are exposed to traumatic events before they are 18 years old; about 15% will develop PTSD which may persist for years if untreated. PTSD is associated with impaired social and academic functioning, poor quality of life, increased suicidal behaviour, and significant comorbidity. Highly effective psychological treatments exist but are not commonly available in the NHS. There is an urgent need to disseminate these effective treatments for PTSD in youth. Methods: The project has 2 phases. In the first phase, we will build software for internet-delivered Cognitive Therapy (iCT) for PTSD. In the second phase, we will evaluate iCT in an RCT (vs Face-to-Face Cognitive Therapy and a Wait List (delayed treatment) condition) to provide feasibility data on acceptability, compliance, retention, and delivery of the intervention, and to provide point estimates of the effect sizes (and confidence intervals) of iCT on PTSD and co-morbid problems. Results: Software development is progressing. Funding: Medical Research Council

Emotional and Behavioural Disorders

Multi-centre aggression subtyping research in conduct syndromes (MATRICS)

Investigators: Dr Michael Craig1, Ilyas Sagar-Ouriaghli2, Mathilde Mastroianni2, Prof Paramala Santosh2,3 & the MATRICS/AGGRESSOTYPE consortium 1 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Child & Adolescent Psychiatry, IoPPN, KCL; 3 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD) Research Team, South London and Maudsley NHS Foundation Trust.

Lay Summary: MATRICS/AGGRESSOTYPE is a study running across 11 European countries. The aim of the study is to identify the neural, genetic and molecular factors involved in the development of aggression/ antisocial behaviour in both normally developing adolescents, and children and adolescents with Attention-Deficit Hyperactivity Disorders (ADHD) and/or Conduct Disorder (CD). This will involve testing both animals and humans on a variety of measures, including neuroimaging and genetic markers alongside questionnaires and tasks. It is hoped that the outputs from this study will find new ways of predicting aggression, and personalised treatment and prevention programs for overt aggression. State of Progress: Ongoing Abstract: Background: Children and adolescents with oppositional defiant disorder (ODD) or conduct disorder (CD) show a repetitive and persistent pattern of aggressive behaviour. One can distinguish between different forms of aggression, such as uncontrolled, emotional, “impulsive aggression” and planned, goal-directed “instrumental aggression”. Another distinction is based on the presence of callous-unemotional (CU) traits, defined as a lack of prosocial emotions. These subtypes may be mediated by unique underlying mechanisms. More knowledge is needed about the behavioural, cognitive, neural and (neuro) biological as well as genetic bases of aggression in childhood- and adolescent-onset CD and/or ODD. Methods: MATRICS will test the hypothesis that different aggression phenotypes result from impaired arousal mechanisms, which in turn dysregulates three basic neural functions: regulation of control mechanisms of aggression, emotional value rating of others, and empathy and moral decision making. Current classifications of aggression phenotypes will be deconstructed into these three neural systems that are coupled with hypo- and hyper-arousal mechanisms. To study these functions, the project will employ the same psychological tasks in both animal aggression models and human disruptive behaviour disorders samples, with the assessment of neural, neurochemical, genetic, autonomic nervous system and endocrinologic markers. Results & Conclusions: Data collection and analysis is still ongoing, therefore no results have been published or conclusions reached. Funding: EU FP7, BRC Publications: Pending 97

CAMHS CAG Projects Day 2018

Anger rumination in adolescence

Investigators: Dr Kate Prentice1, Dr Lorna Taylor1 & Dr Kate Johnston1,2 1 National & Specialist CAMHS for Adolescent At-risk and Forensic Service, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: Rumination is characterised by repetitive negative thoughts focused on the causes and consequences of negative mood. It has been found to be related to increased and prolonged symptoms of depression and has been more recently explored in relation to anger. Research with adults has consistently found a relationship between anger rumination and angry mood, as well as with related aggressive behaviour. Research with adolescents is emerging, and has had similar findings, although relationships between rumination and age and gender are unclear. There has been recent interest in the type of anger related to rumination. State of Progress: Complete Abstract: Background: The present study provides the first investigation of the relationship between anger rumination and both reactive and instrumental anger in an adolescent sample, whilst also exploring the relationship between anger rumination and verbal and physical aggression. The study controlled for known correlates of rumination and anger: irritability, age, gender and internalising symptoms. Methods: One hundred and eighty-seven secondary-school students took part in this cross-sectional study, completing questionnaire measures and reporting on recent verbal and physical aggression. Exclusion incidents related to anger and aggression were reported by the school. Results: The study found a significant positive relationship between anger rumination and both types of anger even when controlling for irritability, which was a novel finding. It also found a significant positive relationship between anger rumination and self-reported verbal and physical aggression, although school-reported data were too minimal to allow analysis. No age or gender effects were identified. Conclusion: The findings indicate that anger rumination may be a target for clinical interventions for problematic adolescent anger and aggression. Further investigation of the mechanisms by which it relates to anger and aggression is necessary, particularly to inform future treatment approaches. Funding: Funding from Kingâ&#x20AC;&#x2122;s College London Doctorate in Clinical Psychology programme Publications: Pending

Emotional and Behavioural Disorders

Assessing effective participation in vulnerable juvenile defendants

Investigators: Dr Kate Johnston1,2, Dr Kate Prentice1, Hannah Whitehead1, Dr Rhianna Watts1, Dr Lorna Taylor1 & Dr Troy Tranah1,2 1 National & Specialist CAMHS for Adolescent At-risk and Forensic Service, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: As a forensic psychology service working with adolescents we are frequently asked by solicitors to assess vulnerable young people involved in court cases and to consider their ability to ‘effectively participate’ in their trial proceedings. Effective participation is the ability to understand and take an active part in a court trial. To date, there is no standardised assessment which can help clinicians in answering this question. Most young people referred for an effective participation assessment have been adolescents with existing developmental disorder diagnoses such as ADHD, autism spectrum disorders, speech and language disorders and/or learning disabilities. A large proportion also has additional emotional and behavioural problems. National statistics also support our data suggesting that vulnerable defendants have poor literacy skills (e.g. Prison Reform Trust, 2009) 25% of young offenders are said to have reading skills below those of the average seven-year-old and up to 60% have communication disorders (Bryan et al., 2007). The aim of the project was to develop an interactive assessment for vulnerable young people who are involved in court proceedings. The material will be accessible to adolescents with developmental disorders such as autism, ADHD and/or learning disabilities and will assess their ability to understand and participate in a trial. State of Progress: Completed Abstract: Background: Effective participation in trial is outlined under article 6 of the European Convention on Human Rights and refers to the ability to understand and engage in trial. Juvenile defendants are often referred to psychologists or psychiatrists by their solicitors to establish ‘effective participation’ capacity. In the USA, key components to participate effectively are defined and standardised assessments available. In the UK, no formal measures exist. Methods: A consecutive series of 20 adolescents aged 12–20 years, referred by their solicitors to our service, were assessed using a standardised battery and a semi-structured interview designed to assess effective participation. Results: Fifty-five per cent had at least one neurodevelopmental disorder. Low IQ was common and 50% had age-equivalent language scores below 10 years. Rates of depression, anxiety and PTSD were high. Knowledge about trial was poor. Conclusion: These findings have implications for Criminal Justice System professionals and to ensure fair trials for young defendants.

CAMHS CAG Projects Day 2018

Funding: This work was supported by the Maudsley Charity [grant number 798]. Publications:

Johnston K, Prentice K, Whitehead H, Taylor L, Watts R & Tranah T. (2017). Assessing effective participation in vulnerable juvenile defendants. The Journal of Forensic Psychiatry & Psychology; 27(6): 802-14.

Assessing knowledge of court proceedings in 10 and 14-year old children

Investigators: Dr Kate Johnston1, Dr Kate Prentice1, Hannah Whitehead1 & Dr Troy Tranah1,2 1 National & Specialist CAMHS for Adolescent At-risk and Forensic Service, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: Little is known about children and adolescent’s knowledge of court trials. As part of a larger project to develop a way of assessing knowledge and understanding of court trial in vulnerable child defendants, we wanted to find out what 10 and 14 year old children know about going to court. Sixty children from mainstream primary and secondary schools took part in the project, completing a newly developed interactive measure of effective participation. This data will be used to provide us with information regarding the level of understanding that a child of this age might reasonably be expected to have. Ten years is the current UK age of criminal responsibility so data from children of this age would be important in discussing the results of older adolescents with developmental disorders who may be involved in the criminal justice system. Abstract: Background: We have recently developed a new measure to assess juvenile defendants’ ability to effectively participate in their court trial in England and Wales. The aim of the current study was to provide an initial picture of the typical understanding of trial processes of children aged 10 and 14. Methods: The sample consisted of 60 typically developing school children aged 10 and 14 years old, recruited from two mainstream schools in South-East London. All children completed the effective participation interview and a measure of verbal IQ. Language ability was also assessed. Results: IQ and age positively correlated with knowledge of court trial participants and processes. However, results showed very low levels of knowledge across all children, with 10-year olds correctly answering only 12% of questions correctly and 14-year olds only correctly scoring 17%. Conclusion: These finding have implications for adequately educating young defendants who are involved in the court process and for professionals working in the criminal justice system to ensure that their clients receive a fair trial.

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Funding: This work was supported by the Maudsley Charity [grant number 798]. Publications: Pending

Language and social skills in teenage girls at-risk and not at-risk of future offending

Investigators: Dr Emmie Neophytou1, Dr Lorna Taylor1 & Dr Kate Johnston1,2 1 National & Specialist CAMHS for Adolescent At-risk and Forensic Service, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: There is a growing evidence base showing that male young offenders present with language and social problem-solving difficulties and that this may underlie their behavioural problems. There is a lack of research looking at the rates of these difficulties in females and a general assumption that language is better developed in this group. There is a need to develop the evidence base in this area to allow advances to be made in terms of services for females who offend or are at risk of offending. State of Progress: Completed Abstract: Background: This study aimed to explore whether females at risk of offending show impaired oral language and social skills competence, relative to their age and IQ matched peers, and if so, what nature of deficits might contribute to the development of antisocial behaviour in this group. Methods: In total, 48 girls aged between 14 and 16 years were recruited to take part in the study; 24 at high risk (HR) of offending and 24 at low risk (LR). Participants completed a range of standardised measures of intellectual ability, expressive, receptive and everyday language ability, as well as screening measures for attention, depression and anxiety related difficulties. Results: HR females had poorer receptive vocabulary, lower levels of language output and demonstrated a trend towards poorer narrative structure. HR females had adequate social use of language and were â&#x20AC;&#x2DC;superficiallyâ&#x20AC;&#x2122; language competent. HR females presented with deficits in social problem-solving which were independent of language ability, inattention and hyperactivity, depressive symptom severity or intellectual ability. Increased levels of inattention and depressive symptoms were also found among HR females. Conclusion: The findings highlight that HR females, similarly to males, present with deficits in language and social skills which may contribute to the development and maintenance of antisocial behaviour. The findings

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have implications for psychosocial intervention and advocate a role for early, multi-modal, systemic intervention designed to target these areas of need, as well as the offending or antisocial behaviour. The findings also have implications for female-specific interventions in the youth justice system. Funding: Funding from King’s College London Doctorate in Clinical Psychology programme Publications: Pending

Prevalence and patterns of diagnostic transitions in child and adolescent mental health services

Investigators: Dr Cliodhna O’Connor1,2, Prof Fiona McNicholas2,3,4 & Dr Johnny Downs5,6 1 School of Psychology, University College Dublin; 2 School of Medicine, University College Dublin; 3 Our Lady’s Children’s Hospital Crumlin, Dublin; 4 Lucena Clinic, Rathgar, Dublin; 5 Department of Child &Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 6 NIHR South London and Maudsley NHS Foundation Trust Biomedical Research Centre.

Lay Summary: Many young people attending in Child and Adolescent Mental Health Services (CAMHS) will, over the course of their engagement with mental health services, experience a change in their primary diagnosis. These diagnostic transitions can occur for many reasons, including the onset of new symptoms, differences of clinical opinion, and revision of the criteria that are used to diagnose particular conditions. Qualitative evidence suggests young people can experience confusion when their diagnoses change, because diagnostic labels are often very important in helping young people make sense of their emotional and behavioural difficulties. Despite the many contexts in which diagnostic changes can occur and their potentially profound effects, no research has either quantified their prevalence or established the typical contexts in which they manifest. That is, what proportion of children who attend CAMHS undergo a diagnostic change during their service engagement? What are the most common reasons for a young person’s diagnosis to be changed? Does one type of diagnosis consistently shift into another category? Are diagnostic transitions systematically precipitated by certain factors, e.g. change of clinician, emergence of specific symptoms or onset of adolescence? Are they related to demographics such as gender? This project aims to answer such questions via quantitative analysis of data from CAMHS clinical records. State of Progress: Ongoing Abstract: Background: Epidemiological data shows that psychiatric diagnoses in childhood have limited temporal continuity. Over the course of a child’s contact with mental health services, a diagnosis received at one time can transition into a different diagnostic classification, be supplemented by additional comorbid diagnoses, or be lost entirely (Copeland et al., 2013; Fein et al., 2013; O’Connor et al., 2018). Such changes may have profound implications for young people and their families, given the significance invested in diagnostic labels as a means of making sense of emotional and behavioural difficulties. However, no research has investigated the prevalence or typical patterns of diagnostic changes in CAMHS. 102

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Methods: This study will draw data from the Clinical Record Interactive Search (CRIS) system operated by the NIHR Maudsley Biomedical Research Centre. Analysis will establish the proportion of CAMHS attendees who experience more than one diagnostic event, and the typical patterns of these diagnostic trajectories. For instance, the analysis will investigate whether certain diagnoses reliably follow others, whether there are particular time-points when new diagnoses are likely, and whether receiving multiple diagnoses is related to any demographic or clinical variables. The study will also examine the context of diagnostic events to chart the range of reasons a new diagnosis may be mentioned in CRIS clinical notes. A representative sample of diagnostic events will be manually coded to indicate the reasons for each new diagnosis, which may include the addition of a comorbid diagnosis, differential diagnosis, revision of a prior diagnosis due to change in symptomatology or differing clinical opinion, informal notes querying the possibility of a certain diagnosis, or proposal of a potential diagnosis with full assessment deferred. Funding: Marie Sklodowska-Curie Individual Fellowship; Royal Irish Academy Charlemont Grant. JD is supported by Psychiatry Research Trust Peggy Pollak Fellowship and the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and Kingâ&#x20AC;&#x2122;s College London. Publications: Pending

MILESTONE study: Development and validation of a suite of measures to manage and strengthen transition from child to adult mental health care

Investigators: Mathilde Mastroianni1, Natalie Heaney1, Ilyas Sagar-Ouriaghli1, Dr Laura Adams1, Dr Kate Lievesley1, Dr Federico Fiori1,2,3, Dr Jatinder Singh1, Prof Paramala Santosh1,2,3 & the MILESTONE consortium 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD) Research Team, South London and Maudsley NHS Foundation Trust; 3 HealthTracker Ltd, Gillingham, Kent.

Lay Summary: The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the major socioeconomic and societal challenge related to the transition process. The study is running across 8 countries across the EU and follows young people on their transition journeys from Child and Adolescent Mental Health Services (CAMHS) to Adolescent Mental Health Services (AMHS). The core goal of the study is to find ways to determine the effectiveness of a model of managed transition in improving health & social outcomes. State of Progress: Ongoing

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Abstract: Background: Mental health disorders and psychopathology are prevalent in young people approaching the transition boundary. Despite this, transition from Child and Adolescent Mental Health Services (CAMHS) to Adolescent Mental Health Services (AMHS) is often inadequate resulting in many young people falling between the gaps. Obstacles to an optimal transition include poor planning, differences in service culture and policy gaps. In an attempt to address factors such as these, the MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) suite of measures has been developed to manage/strengthen transition. These aim to provide a structured & objective means of assessing both, the young personâ&#x20AC;&#x2122; readiness/need for transition and how effective the young person/clinicians feel it is. Methods: The MILESTONE project developed two measures: Transition Readiness and Appropriateness Measure (TRAM) and Transition Related Outcome Measure (TROM). The TRAM is designed to be a decision-making tool for clinicians to enable them to identify cases for which transition from CAMHS to AMHS is advisable and appropriate, or for individuals that be safely discharged or referred to a community based service. The TROM is designed to test the outcome of transition. Both of these measures will facilitate and improve healthcare outcomes regarding transitions for young people. The process of development followed an incremental step-wise framework and involved focus groups of service users, parents, families and clinicians. Results: The validation process involves ensuring that the developed measures are valid and reliable. All 3 versions (young person, parent/carer and clinician) of the scales will be validated in all languages used by the EU consortium. Construct validity, content validity, inter-rater validity, test-retest validity and sensitivity to change will be also be assessed. Conclusion: Data for validation is still being collected from participants involved in the two and a half year project. When validated, it is hoped that both of these measures will facilitate and improve healthcare outcomes regarding transitions for young people across the EU. Funding: This research was funded by the European Communityâ&#x20AC;&#x2122;s Seventh Framework Programme (FP7/20072013) under grant agreement no. 602442. Publications: 1.

2. 3.

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Signorini G, Singh SP, Boricevic-Marsanic V. et al. (2017). Architecture and functioning of child and adolescent mental health services: a 28-country survey in Europe. Lancet Psychiatry. 4: 715-724. Signorini G, Singh SP, Marsanic VB. et al. (2018). The interface between child/ adolescent and adult mental health services: results from a European 28-country survey. European Child & Adolescent Psychiatry. 27(4):501â&#x20AC;&#x201C;511. Singh SP, Tuomainen H, Girolamo G. et al. (2017). Protocol for a cohort study of adolescent mental health service users with a nested cluster randomised controlled trial to assess the clinical and cost-effectiveness of managed transition in improving transitions from child to adult mental health services (the MILESTONE study). BMJ Open. 7(10): e016055.

Eating Disorders and Associated Conditions

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Fear of food - Attention bias for food cues in adults and adolescents with anorexia nervosa

Investigators: Dr Jessica Werthmann1,2, Dr Mima Simic3, Dr Anna Konstantellou3, Phoebe Mansfield3 & Prof Ulrike Schmidt1 1 Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Unit of Clinical Psychology and Psychotherapy, Institute of Psychology, Albert-Ludwigs Universität Freiburg, Germany; 3 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: Anorexia Nervosa (AN) is a severe mental disorder, characterised by overvaluation of one’s shape and weight and, related, fear of gaining weight resulting in severe food restriction. The extent of restrictive food intake in people with AN to a life-threatening extent, especially in western, foodrich environments, is worrisome. This avoidance of food intake is thus a hallmark feature of AN that requires a better scientific understanding. Previous research suggested that people with AN may have learned to automatically control how they interact with a food-rich world in a way that helps them to suppress their hunger and craving. One potential process involved is attention allocation for food. Patients with AN may have learned to selectively look away from food. Previous research showed that the longer people spent looking at food the more they ate subsequently. Accordingly, the current research aimed to investigate attention allocation for food cues in people with and without AN across different age groups (adolescents and adults). State of Progress: Completed (Manuscripts in preparation) Abstract: Background: Previous research showed that adults with Anorexia Nervosa (AN) display reduced attention for food cues (i.e. attentional avoidance). Yet, currently it is unclear if similar biases can be observed in adolescents with Anorexia Nervosa. The aim of the current study was to compare attention processes when confronted with food stimuli between adults and adolescents with and without AN. Methods: Attention allocation for food stimuli was measured during a computerised visual probe paradigm with concurrent assessment of response latencies and eye-movements. Results: Adults with AN showed significant avoidance of food stimuli, compared to adolescents with AN. Adolescents with AN did not differ in their attention for food cues from adolescents without AN. Adults with AN showed a pattern of approach-avoidance attention allocation for food cues, compared to adults without AN. Conclusion: The results suggest that attentional avoidance may be a learned automatic cognitive strategy that helps to facilitate food restriction. However, this bias cannot (yet) be observed in adolescents with AN. This research highlights the need for early interventions for AN before cognitive biases facilitating chronic food restriction become too manifested

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Funding: Dr Werthmann was supported by a Rubicon grant of the Dutch Organization for Scientific Research (NWO). Publications: Publications in preparation

Social information processing in adolescents with eating disorders

Investigators: Katie Rowlands1, Dr Mima Simic2, Prof Janet Treasure1 & Dr Valentina Cardi1 1 Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: A proportion of people with eating disorders are socially isolated and have difficulties interacting with others. It is unclear what mechanisms underlie these difficulties and their impact on eating disorder symptoms. We propose that sensitivity to social rejection and a tendency to focus on negative feedback from others are two of the mechanisms that explain social difficulties and abnormal eating behaviours in eating disorders. Adolescents aged 13-17 years with an eating disorder diagnosis and healthy adolescents will be compared on their responses to a battery of questionnaires and computerised tasks. The findings of this study will contribute to the development of a therapeutic module to increase resilience in social situations, by reducing the unhelpful tendency to perceive social stimuli in a negative way, and in turn reduce unhelpful eating behaviours. State of Progress: Ongoing Abstract: Background: A proportion of young people with eating disorders report social and interpersonal difficulties. However, the mechanism underlying these difficulties and how these problems relate to the use of abnormal eating behaviours is unclear. Methods: Adolescents aged 13-17 years with eating disorders (n=80) and healthy controls (n=80) will complete a battery of questionnaires and computerised tasks to assess social functioning, cognitive processing of social stimuli and abnormal eating behaviours. Results: The results of this study will establish whether there are differences in cognitive processing of social stimuli between adolescents with eating disorders and healthy adolescents. The results will also establish whether social difficulties are linked to abnormal eating behaviours. Conclusion: The findings of this study will contribute to the development of a therapeutic module to increase resilience in social situations, through modifying the unhelpful tendency to perceive social stimuli in

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a negative way (i.e. cognitive biases towards negative social stimuli), and in turn reduce the use of unhelpful eating behaviours. Funding: Professor Janet Treasure’s Research Support Account (Slush Fund) Publications: 1.

Cardi V, Di Matteo R, Corfield F & Treasure J. (2013). Social reward and rejection sensitivity in eating disorders: An investigation of attentional bias and early experiences. World Journal of Biological Psychiatry, 14(8):622-33. 2. Cardi V, Di Matteo R, Gilbert P & Treasure J. (2014). Rank perception and selfevaluation in eating disorders. International Journal of Eating Disorders, 47(5):543-52. 3. Cardi V, Esposito M, Bird G, Rhind C, Yiend J, Schifano S, Hirsch C & Treasure J. (2015). A preliminary investigation of a novel training to target cognitive biases towards negative social stimuli in anorexia nervosa. Journal of Affective Disorders, 188:188-93. 4. Cardi V, Turton R, Schifano S, Leppanen J, Hirsch CR & Treasure J. (2017). Biased interpretation of ambiguous social scenarios in anorexia nervosa. European Eating Disorders Review, 25(1):60-64. 5. Turton R, Cardi V, Treasure J & Hirsch CR. (2018). Modifying a negative interpretation bias for ambiguous social scenarios that depict the risk of rejection in women with anorexia nervosa. Journal of Affective Disorder, 227:705-12.

Development of the child and adolescent over and under controlled traits measure (OUT-M)

Investigators: Paige James1, Dr Sarah Carr2 & Dr Catherine Stewart3 1 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Neuroimaging, IoPPN, KCL; 2 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: The purpose of the study is to validate with children and adolescents a questionnaire measuring over and under controlled personality traits. This is because excessive over control has been linked to particular mental health difficulties, including chronic depression and anorexia nervosa. Consequently, a specific treatment (Radical Openness Dialectical Behaviour Therapy) has been developed to target excessive over control. However, not every individual presenting with these mental health problems will have excessive over control, and so it is important to be able to measure these traits so that appropriate treatment can be offered to individuals. Secondary school children in South London were given a 70-item questionnaire in order to establish which items capture the global personality types “over control” and “under control” in children and adolescents. The 70-item questionnaire is based on previous research measuring these personality traits in adults. Overall, 25 items were found to successfully capture over control and under control, with 14 measuring over control and 11 measuring under control in young people. These items create a screening questionnaire for measuring over control and under control in children and adolescents. State of Progress: Ongoing Abstract: Background: Over control and under control are two global personality traits (Block & Block, 1980). Excessive 108

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over control and excessive under control have both been linked to mental health problems, with over controlled individuals experience more internalising conditions, such as depression, while under controlled people experience more externalising conditions, such as delinquency and substance misuse (Klimstra, et al., 2010; Hart, et al., 2005; Akse, et al., 2007). It has been argued that treating these personality traits would have a longer lasting impact mental health. Radically Open Dialectical Behavioural Therapy (RO-DBT; Lynch et al., 2013) has been developed to treat conditions associated with maladaptive over control. Thus far efficacy has looked at adults with promising findings in depression (Lynch et al., 2003; 2007), over controlled treatment resistant individuals (Keogh et al., 2016) and pilot findings for anorexia nervosa (Lynch et al., 2013; Chen et al., 2015). RO-DBT is being adapted for children and adolescents by the Child and Adolescent Eating Disorder service in SLAM. The profile of young people presenting to services with anorexia nervosa is diverse and not all of these individuals will have maladaptive over control. It is necessary to identify those that do in order to offer appropriate treatment to individuals. Seretis et al. (2017) developed the Over Control and Under Control Traits Measure (OUT-M) in adults. Based on this, the present study aims to establish a measure of over control to form a screening measure for young people with anorexia nervosa to identify those suitable for RO-DBT. Methods: Six hundred and seventeen young people aged 11-18 years were recruited from two secondary schools in South London. All participants were given a modified Over and Under Controlled Traits Measure (OUT-M; Seretis et al., 2017) which included an â&#x20AC;&#x153;I donâ&#x20AC;&#x2122;t know what this meansâ&#x20AC;? option. In addition, demographic information and the Positive and Negative Affectivity Scale (Watson, Clark & Tellegen, 1988) were completed. Following data collection, participant responses were screened with any individual with greater than 20% of data missing being excluded from further analysis. This was in line with the cut-off employed in the adult OUT-M study (Seretis et al., 2017). The remaining participants (n = 412) went forward into analysis. The second aspect of data cleaning concerned the specific OUT-M traits. Traits were removed if there was violation of normal distribution parameters, there was a correlation >0.4 with either PANAS subscale or if the specific trait had no correlations greater than 0.4 with at least one other trait. After trait cleaning the remaining traits went into factor analysis. The factor analysis plan for the study was as follows: (1) Exploratory factor analysis of all traits (2) Refined factor analysis specifying number of traits based on initial exploration (3) Factor analysis of female respondents only In addition, in order to ensure a valid measure of over control in children and adolescents, the data associated with participants excluded from analysis was analysed to ensure there were no significant differences between included and excluded participant characteristics. Results: Participant screening measures produced a final sample size of 438 participants. Trait screening reduced the initial 70 traits to 37. The first exploratory factor analysis produced a nine-factor solution, however based on the Scree plot and eigenvalues, a three-factor structure appeared more suitable. Following this a factor analysis specifying three factors was conducted. This indicated that only five factors loaded onto the third factor. A 2-factor analysis was run and produced the final solution. The final solution included 25 traits, with 14 traits loaded onto Factor 1 and 11 onto Factor 2. Factor 1 traits are: Cautious, Disciplined, Formal, Hardworking, Obedient, Orderly, Organised, Patient for reward, Perfectionist, Precise, Proper, Punctual, Think before acting, and Tidy. Factor 2 traits are: Aggressive, Bossy, Careless, Chaotic, Extreme, Fearless, Misbehaving, Rebellious, Risky, Stubborn, and Wild. 109

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Based on the loaded traits, factor 1 was labelled over control and factor 2 over control. Female-only analysis confirmed the findings of the overall sample and excluded participant analysis yielded no significant biases. Conclusion: The present study was successful in creating a measure of over and under control in children and adolescents. A 25-item measure prevailed that captures under and over control in young people to be used as a screening measure for RO-DBT. Funding: This project is being completed in partial fulfilment of a Masters degree. Publications: N/A

Impact of autism spectrum disorder traits on treatment outcomes of eating disorders in girls

Investigators: Dr Catherine Stewart1, Dr Fiona McEwen2, 3, 4, Dr Anna Konstantellou1, Prof Ivan Eisler1 & Dr Mima Simic1 1 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust; 2 Department of Child and Adolescent Psychiatry; 3 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 4 Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London.

Lay Summary: This is an audit of the data from girls with restrictive eating disorders referred to the Child and Adolescent Eating Disorder Service (CAEDS) between September 2009 and October 2015. It addresses the following questions: (1) Are levels of ASD traits elevated in this sample of girls with restrictive eating disorders? (2) Do elevated levels of ASD traits result in greater need for augmentation of treatment? (3) Do elevated levels of ASD traits result in poorer outcomes at the end of treatment? It finds that: (1) Current ASD traits are elevated but is not a concurrent elevation in parent reported developmental concerns from early childhood. (2) Treatment was augmented more often for those with high levels of ASD traits, but that this was accounted for by symptoms of depression rather than ASD. And (3) That physical health outcomes did not differ between those with high and low ASD traits, but that those with high ASD traits had less improvement in the cognitive elements of an eating disorder. State of Progress: Completed Abstract: Background: Autism Spectrum Disorders (ASD) are more commonly diagnosed in males than females, but are over-represented within the predominantly female adult eating disorder (ED) population (Huke, Turk, Saeidi, Kent, & Morgan, 2013; Mandy & Tchanturia, 2015; Rhind et al., 2014). Evidence links high levels of Autism Spectrum Disorder Traits in women with chronicity of anorexia nervosa. Less is known about the presentation of ASD traits in children and adolescents with EDs. Restrictive 110

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EDs are potentially life threatening with little known about predictors of treatment response or the development of chronicity (Wonderlich et al., 2012). The long-term outcomes for teenage-onset AN at 6-, 10- and 18-year follow-ups are poorer for those who have met criteria for a diagnosis of ASD (Nielsen, Gillberg, Gillberg, Råstam, & Wentz, 2015). These papers are the product of large scale population study of people born between 1970 and 1974. The treatment of EDs has changed considerably since this cohort would have been adolescents, and little is known about the impact of ASD traits on response to current treatment in young people. Methods: This study was an audit of the treatment outcomes of girls referred to a specialist outpatient child and adolescent ED service in London (being the main service provider for a catchment area population of just under 2,000,000) between September 2009 and October 2015 who were female, diagnosed at assessment with AN (DSM-IV or DSM-5) or restrictive subtype Eating Disorder Not Otherwise Specified (EDNOS-R, DSM-IV) or other Specified Feeding or Eating disorder/ Atypical Anorexia (OSFED, DSM-5). This is an audit of the impact of ASD traits on clinical outcomes for treatment of restrictive EDs addressing the following questions: (1) Are levels of ASD traits elevated in this sample of girls with restrictive eating disorders? (2) Do elevated levels of ASD traits result in greater need for augmentation of treatment? (3) Do elevated levels of ASD traits result in poorer outcomes at the end of treatment? Results: (1) 6.9% (20/289) had a score on the AQ above the cut-off of 30 (Baron-Cohen et al., 2006). BaronCohen et al. report that none of their female control group scored 29+. 15.4% (52/338) of girls’ scores were below 16 on the SAS, indicative of reduced social aptitude (Liddle et al., 2009). Analysis comparing the distribution of DAWBA computer generated predictions of probability of presence of ASD between the current sample and that derived from the BCAMHS04 sample (Goodman, personal communication; mean age 15.0, s.d. 0.8) with the population norms as the reference data did not reveal a significant difference (ᵪ2 = 8.60, df = 5, p> .05). (2) Chi squared analyses of augmentation of treatment for groups with high and low ASD traits as indexed by the AQ (cut-off of 30) revealed proportionally greater augmentation of treatment for the high AQ group (ᵪ2 = 7.30, df = 1, p< .01) reflected in both admission to an intensive day patient programme (ᵪ2 = 6.21, df = 1, p< .025) and to psychiatric wards (ᵪ2 = 8.68, df = 1, p< .005) but not in greater use of paediatric medical admission (ᵪ2 = 0.27, df = 1, p> .05). Given the potential confound between parent reports of ASD and depression and anxiety, a binary logistic regression was performed to analyse the predictive utility of AQ on treatment augmentation after controlling for parent reported depression and anxiety. This revealed parent reported depression (B = 0.04, p< .01) as a significant predictor of the need for treatment augmentation, with neither anxiety nor AQ score making a significant contribution to the model (both p> .77). (3) Physical outcome at discharge were compared using the Morgan Russell criteria for physical health. Chi squared analyses of the difference in distribution between outcome categories for the high and low ASD trait groups, as indexed by AQ and SAS did not reveal significant differences in distribution of outcomes (all ᵪ2< 3.02, df = 2, all, p> .05). At discharge, correlations between indices of ASD traits and change scores on symptom outcome measures were non-significant except between DAWBA ASD score and the EDEQ subscales of weight concern, shape concern and the global score (all p< .004). Less change was associated with higher DAWBA ASD scores. Conclusion: This audit has demonstrated a clear elevation in current ASD traits measured by the AQ and SAS above what would be expected in the general population. However, there was no evidence of increased ASD-related early childhood developmental concerns, measured using the ASD module of the DAWBA. The replication of the finding (Pooni et al., 2012) that elevated ASD traits in an eating disordered group do not co-occur with parental reports of early developmental difficulties consistent 111

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with ASD highlights the need for further understanding of the aetiology and diagnostic significance of elevated ASD traits in EDs. It has further demonstrated that treatment as usual offered by this service does not result in statistically different physical outcomes for girls with elevated levels of ASD traits. However, it is notable that there is some evidence of an attenuation of change in the cognitive symptoms of EDs for those with higher levels of ASD related developmental concerns, alongside a greater need for treatment augmentation during treatment, which is indicative of a need for further research to elucidate the associations between neurodevelopment, starvation, psychological distress and persistence into adulthood of AN. Funding: Own account Publication:

Stewart CS, McEwen F, Konstantellou A, Eisler I & Simic M. (2017). Impact of ASD traits on treatment outcomes of eating disorders in girls. European Eating Disorders Review, 25:123-128.

When the world seems pro-ana: Adolescents’ experience of social media and eating disorders

Investigators: Faith Brammer1, Dr Catherine Stewart2 & Dr Beth McDermott3 1 Department of Psychology, University of Bath; 2 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust; 3 Northamptonshire Child and Adolescent Eating Disorder Service.

Lay Summary: Young people’s use of social media has escalated over recent years and in comparison to the detailed research examining pro-ana communities online, little is known about the experiences of young people with eating disorders as they interact with social media. This qualitative study used semi-structured interviews with ten young people with restrictive eating disorders to find out from them how they viewed the impact of social media on themselves. The research revealed three themes: (1) When the world seems pro-ana, (2) Trapped by a sense of belonging and (3) The adults don’t get it. State of Progress: Completed Abstract: Background: Research suggests that social media can play a role in both the development and maintenance of eating disorders in young people but also that its use may offer protective benefits. Social media has changed the way in which young people interact: 76-81% of adolescents regularly use social media platforms (Lenhart, 2015). A significant body of research has explored the relationship between online content and eating disorders. The cultural pervasiveness of the ‘thin ideal’ has become entrenched in the internet mainstream (Hawkins, Richards, Granley & Stein, 2004; Ricciardelli, Clow & White, 2010) while the formation of online communities which conceptualise eating disorders as a lifestyle ‘choice’ can reinforce disordered eating behaviours and prevent help seeking (Norris, Boydell, Pinhas & Katzman, 2006; Rouleau & von Ranson, 2010). Appearance comparisons between self and the multitude of online images mediate between social media use and body image dissatisfaction

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(Fardouly & Vartanian, 2015). However, online communities accessed via social media may also have a positive function through facilitating social connection, support and a sense of belonging (Aardoom, Dingemans, Boogaard & van Furth, 2015; Arseniev-Koehler, Lee, McCormic & Moreno, 2016) which has been conceptualised as key to recovery (Federici & Kaplan, 2008; Noordenbos & Seubring, 2006), particularly as this population tend to have a poorer quality of social network than their peers (Patel, Tchanturia & Harrison, 2016). The apparent contradiction between damaging and protective elements of social media use, and its ubiquitous presence in the lives of young people, presents a dilemma for clinicians and parents/carers, and may prevent young people from feeling able to readily disclose their online experiences. Existing research has been predominantly experimental or questionnaire based, and largely with community samples of adolescents or young adults. This research therefore explores the experiences of adolescents with an eating disorder, whose voices thus far have been missed. Methods: A qualitative design was chosen to capture young people’s personal experiences and understanding of social media in detail. The research adopted a critical realist epistemological position, as it was assumed that while the data accurately described how young people used social media, further interpretation was required to fully understand its impact (Willig, 2008). Data was analysed using thematic analysis. Individual semi-structured interviews were conducted with ten young people (9 female and 1 male). Results: The analysis identified three overarching themes: (1) When the world seems pro-ana, (2) Trapped by a sense of belonging and (3) Adults don’t get it. Exposure to content on social media that maintained disordered eating was considered to be constant, intrusive and difficult to control. Participants described triggering content as being quickly accessible, even if they tried to avoid it, for example, associated with other hashtags or recommendations from social media sites, meaning extreme content could become normalised through frequent exposure. Though many mentioned the negative impact of content explicitly promoting the thin ideal (e.g. ‘thinspiration’) and the concept of eating disorders as a lifestyle choice, there was also an emphasis on the significant triggering capacity of seemingly benign content which was experienced as pervasive (such as weight loss tips, exercise/ fitness pages, recipe/healthy eating pages and posts online of people’s meals). This was deemed as unavoidable on social media, despite attempts to avoid triggering content. Online connections were perceived to be of the utmost importance, particularly by those whose physical contact with friends had been limited by the eating disorder. Some participants discussed the ways in which social media enabled connection with others in similar circumstances. The relative anonymity afforded by social media resulted in some opening additional “secret” accounts either to express frustration or negativity relating to mental health issues (venting accounts) or make positive steps forwards to recovery (recovery accounts), without the knowledge or scrutiny from close contacts. Participants identified an overall lack of understanding from their parents and therapists, and clearly stated they were more likely to discuss any issues arising from social media use with their peers. Participants felt it was especially important for therapists to be aware of triggering content, and that young people can access this privately, without restrictions. Participants envisaged therapists having a helpful role in addressing issues arising from social media usage, by providing education regarding healthy diets and staying safe online. They acknowledged that attempts to moderate social activity would be ineffective as young people would access material covertly. Conclusion: The research presented here has confirmed that appearance comparisons and a sense of community are key factors in adolescents’ experience of social media, extending this from community, adult patient and school based samples. Moreover, it has highlighted the difficulty that young people with eating disorders face not only in navigating the eating disorder communities online but also in managing

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their responses to seemingly innocuous posts from friends and celebrities, and their desire for nonjudgemental open spaces in therapy to be able to explore these. Funding: Completed in partial fulfilment of an MSc. Publications: Submitted

Intensive treatment programme (ITP): A service evaluation of the effectiveness of day patient treatment for adolescents with a restrictive eating disorder

Investigators: Dr Mima Simic1, Dr Catherine Stewart1, Prof Ivan Eisler1, Dr Julian Baudinet1, Dr Katrina Hunt1 & Dr Beth McDermott2 1 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust; 2 Northamptonshire Child and Adolescent Eating Disorder Service.

Lay Summary: Admission rates for adolescents with eating disorders have been increasing, alongside an increase in the length of admission. There is a clear rationale for developing effective alternative intensive treatments that can be used to supplement outpatient care in order to promote recovery. The Intensive Treatment Programme (ITP) in the Child and Adolescent Eating Disorder Service (CAEDS) offers day patient treatment for young people. This is a retrospective case file review of all young people treated in ITP between September 2010 and February 2015. Young people made significant improvements during a short admission to ITP including in weight gain, eating disorder symptomatology, motivation to recover, quality of life and comorbid symptomatology. ITP is an effective and brief intervention for young people who require intensification of treatment. State of Progress: Completed Abstract: Background: Family Therapy for Anorexia Nervosa (FT-AN) is the first line treatment for adolescents with anorexia nervosa in the U.K. However, research suggests between 10 and 40% of young people have a poor outcome (Simic et al., 2016). In the UK inpatient admission rates for eating disorders have been steadily rising at the same time as length of stay has increased (Royal College of Psychiatry, 2012). As such there is a clear rationale for developing effective alternative intensive treatments that can be used to supplement outpatient care in order to promote recovery. The Intensive Treatment Programme (ITP) is a day programme for adolescents with predominantly restrictive eating disorders which was developed within the specialist outpatient Child and Adolescent Eating Disorder Service (CAEDS) at the Maudsley Hospital in 2010. Unlike many other day programmes, ITP is not a standalone treatment, but is embedded within a comprehensive outpatient treatment programme. It is offered to around 20% of patients in the service with a restrictive eating disorder (anorexia nervosa, or restrictive eating disorder not otherwise specified), when an increased intensity of treatment is needed to prevent inpatient admission or as a more intensive treatment for young people for whom standard treatment has been insufficient in supporting expected progress towards recovery. It is also used to facilitate quicker discharge for those already in inpatient care. 114

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Methods: Data from a retrospective review of patient files and outcomes on self-report measures were analysed for 107 young people aged 11-18 with predominantly restrictive eating disorders referred to the programme in the first four and a half years of its operation. Weight, height and self-report questionnaire data from the first and last day of ITP attendance. For those patients who remained in the CAEDS service % BMI was extracted from clinical notes six months post ITP (when patients were back in outpatient treatment) and at the point of discharge from CAEDS. Morgan Russell Global Outcome scores at discharge from CAEDS were also rated (Russell et al., 1987). A series of repeated measures ANOVAs was conducted to analyse changes in key physical and psychological measures over the course of treatment. Results: Although young people attended ITP for only on average 29.5 days, results indicate that the programme was effective in generating significant improvements in a range of domain. Young people who completed the ITP programme gained weight, and also reported significant changes on each subscale of the EDE-Q and the EDQLS, reflecting improvement in eating disorder symptoms, including improvements in eating disorder behaviours, cognitions and quality of life. There was a significant change in self-ratings of mood, reflecting an improvement in mood between assessment and discharge from ITP. Scores were firmly within the clinical range prior to commencing ITP, and on the borderline of the clinical range at discharge from ITP. Similarly, there was a significant change over the course of ITP treatment on young peopleâ&#x20AC;&#x2122;s ability to effectively regulate their emotions as measured by the DERS. Young people reported significant improvements in their goal directed behaviour, impulse control difficulties, emotion regulation strategies and lack of emotional clarity. There were no significant differences for self-report of worry or ability to manage worry over the admission to ITP as measured by the PSW-C and the CQ respectively. Following ITP day treatment, 80.4% (n=86) of the young people continued their treatment in CAEDS. Only 10.3% (11) were referred for an inpatient admission. Young people continued to make improvements post ITP in outpatient treatment provided by the same service and 73.2 % had a good or an intermediate outcome at the point of discharge from the service. Conclusion: ITP is an effective and brief intervention for young people who require intensification of treatment. This is the largest cohort reported on to date of young people who have been treated for a restrictive eating disorder in a day patient programme to our knowledge. The results reported here demonstrate that ITP is an effective community-based intervention for young people who require increased intensity of support in addition to expert outpatient treatment. This is a group for whom inpatient treatment would usually be required, which may itself increase the risk of a poor prognosis (Gowers et al., 2000). However, in our sample only 10% had to be referred from ITP for inpatient admission. Significant changes in self-report measures of key factors, including quality of life, self-esteem, mood and emotion regulation, are encouraging as they suggest that despite the short length of the programme, ITP is effective in treating predisposing factors and comorbidities simultaneously with eating disorder symptomatology. Together with the improvement in weight and the ability to engage with outpatient treatment following ITP, this suggests day programmes offer more than just weight restoration; they have the capacity to expedite recovery and facilitate its continuation in an outpatient setting, which is significantly more cost-effective and confers additional advantages in assisting more healthy social development than an inpatient environment. Funding: N/A Publications: Submitted 115

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Outreach to adolescents with symptoms of bulimia nervosa: Increasing accessibility of treatment

Investigators: Dr Catherine Stewart, Dr Rachel Loomes, Phoebe Mansfield, Alice Parker & Richard Hall National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: Bulimia Nervosa (BN) is a chronic mental health condition associated with significant physical health complications as well as high levels of shame, guilt and blame, which prevent early helpseeking behaviour. Treatment for adolescents with Bulimia Nervosa (BN) is under-utilised locally and nationally. The BN Outreach Project run by the Child and Adolescent Eating Disorders Service (CAEDS) aimed to raise awareness of BN in the community and to increase the referral rate of young people to CAEDS. We worked to build relationships and provide outreach support to secondary schools, community groups, youth clubs, GPs and Primary Care networks across seven South East London boroughs. There was an ongoing focus to support ‘hard to reach’ young people from ethnic minority groups, meaning work with youth and community groups with a high proportion of underrepresented young people was prioritised throughout. Accessible outreach material was co-created by CAEDS staff and young people from the local community. Outreach was then provided through workshops, assemblies, and staff training sessions. Awareness posters and leaflets were distributed. Outreach content covered BN Psychoeduation and highlighted the pathways to access help, including promoting CAEDS self-referral pathways. Feedback was collected following outreach in an ongoing manner in order to provide the opportunity for comments and to find out whether there were any potential barriers people still felt would prevent them from accessing help. Since outreach began we have seen an increase in the number of BN type diagnoses and in the number of referrals from young people from ethnic minority groups. State of Progress: Ongoing – data collection continues to September 2018. Abstract: Background: Treatment for adolescents with Bulimia Nervosa (BN) has been under-utilised. The lifetime prevalence rate of BN or BN-NOS for females by age 18 has been estimated to be 1.7%, and AN 2.6% (Isomaa et al., 2009) with no difference in annual incidence between the two disorders (34.6 and 35.8 per 100 000, Currin et al., 2005). In contrast referrals to CAEDS were dramatically lower for BN than for AN (11.5% BN in an audit of consecutive referrals 2009-2012, with only 16 BN referrals in 2015) which indicated a significant unmet need for adolescents with BN. BN is a chronic mental health condition associated with significant physical health complications as well as high levels of shame, guilt and blame, which prevent early help-seeking behaviour. The average duration of illness at first presentation is typically 4-5 years. Delayed help seeking impacts negatively on young people’s psychological and physical well-being and prevents early intervention for the illness as by this point the disorder is well established. The BN Outreach project aimed to raise awareness of BN and highlight the pathways to access help to increase the numbers of adolescents experiencing BN symptoms seeking treatment. Methods: Development phase/Pilot phase (December 2016 – April 2017): During the development phase focus groups and meetings with young people and stakeholders from local communities (geographical area covered included Lambeth, Southwark, Lewisham, Croydon, Bromley, Greenwich and Bexley) were

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used to determine the outreach content. Resources (assembly, workshop, staff training presentations and awareness posters) were co-created and piloted with additional schools to assess suitability. Roll-out phase (May 2017 – April 2018): The process of outreach rollout included identifying/ contacting relevant stakeholders (e.g. school SENCO’s and youth workers). Initial meetings with stakeholders were held, providing opportunities to discuss BN symptomatology, warning signs, prevalence information, pathways to access help and provide awareness posters/leaflets to be circulated to their networks. Subsequent outreach sessions were then arranged. 96 schools were worked with, including providing 69 student assemblies, 13 student workshop days and 36 staff training sessions. Additional outreach to community groups (youth, sports, religious, cultural groups) took place; 44 community groups were supported by working in an adaptable way to tailor outreach to suit different settings. Outreach in youth group contexts ranged from presenting short awareness talks during a football tournament to providing staff training at a borough wide Youth Workers safeguarding events. Information was also shared with GPs, School Nurses and Pharmacies across the geographical area covered. Results: The pre-outreach period (May 2016-March 2017) has been compared to the post-outreach period (May 2017-March 2018). These results are preliminary as data collection will continue until September 2018. Referrals: We have seen an increase of 7.8% in referrals with BN symptoms mentioned at the point of

referral (7.1% vs. 14.8%). There has not been a decrease in the proportion of people offered assessment (69% vs 74%) and then treatment (69% vs 72%), indicating that the increase was not driven by inappropriate referrals caused by our outreach work. There has been an increase in the number of referrals from Black young people (3.1% (n = 7) vs. 6% (n = 16)) and Other Ethnic Groups (.4% (n = 1) vs. 3.4% (n = 9)), meaning 17 more young people from BME groups sought help from CAEDS since the outreach has been running. We have seen a rise in school referrals, young person self-referrals and parent referrals. Parent referrals rose from 12% to 22.8%. Diagnosis: We have seen a rise of 15 extra BN type diagnoses since outreach began, n = 27 (21.43% of

referrals accepted for treatment in CAEDS) vs. n = 42 (27.27%). Clinical outcomes: It is too early in the study to report on whether earlier access to treatment has resulted

in improved outcomes or shortened treatment times. Conclusion: The BN Outreach Project has successfully supported schools and the local community groups covering the geographical area covered by CAEDS. Outreach sessions were consistently well received by young people and adults who support them. There is an encouraging trend of more young people with BN symptoms being referred in, subsequently more BN type diagnosis when comparing pre and post outreach time points. We have not seen an increase in inappropriate referrals. Funding: Guy’s and St Thomas’ Charity, Health Innovation Fund Grant, Dr Catherine Stewart. Collaborators: Dr. Mima Simic and Prof Ivan Eisler. Publications: Pending

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Developing treatments for bulimia nervosa in adolescence

Investigators: Dr Catherine Stewart, Dr Mima Simic & Prof Ivan Eisler National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust

Lay Summary: Bulimia nervosa (BN) is an eating disorder which has profound effects on young people’s emotional and physical health. It is associated with high levels of guilt and shame, and can lead to dental, digestive system and cardiac damage. However, adolescents with BN internationally are prevented from recovery by a reluctance to seek support, lack of knowledge about the availability of treatment and relatively poor outcomes once engaged in treatment. This project seeks to develop treatment pathways for young people that are informed by sub-groups within the diagnostic grouping of ‘Bulimia’ in order to improve treatment outcomes by offering more tailored treatments. State of Progress: Ongoing/Future Abstract: Background: NICE guidelines currently recommend Cognitive Behavioural Therapy for Eating Disorders (CBTED) or Family Therapy for Bulimia Nervosa (FT-BN) for the treatment of BN. However, both of these have a very limited evidence base (with relatively poor outcomes), with abstinence from binge-purging reported in RCTs ranging from 25-45%. This is perhaps not surprising when it is considered that young people have been treated for ‘BN’, when ‘BN’ is considered to have different phenotypes, the clearest of which are 1) psychologically relatively intact but anxious and/or low in self-esteem, and 2) emotionally and behaviourally dysregulated. It is posited that the first group tends to develop BN as a response of the appetite to dieting and body image related difficulties. While for the second BN can be formulated within a constellation of responses to emotional and social difficulties which often includes self-harm, in addition to diet and body image related difficulties. The development of treatments for BN has been hampered by the difficulties young people experience in seeking help and by a diagnostic approach that does not take into account the differing needs presented by varying bulimic phenotypes and the need to simultaneously treat comorbidities. Methods: Our main aim is to develop treatments and treatment pathways for BN and comorbid self-harm tailored to address individual profiles of presentation and therefore improve the outcomes for young people, who are not served well by the existing approaches internationally. This has led to the development of a multi-staged project. Phase 1: Development

The team has developed Multi-Family Therapy for Bulima Nervosa (MFT-BN; Stewart et al., 2015) to address some of the limitations of both CBT-ED and FT-BN. We have worked with B-EAT, the eating disorders charity, to conduct online focus groups to understand for young people why support is not sought and learn from them how to overcome this. We have then worked with the local community, through a Guys and St Thomas Health Innovation Fund grant, to develop an outreach approach to increase young people’s help seeking behaviours. This has resulted in an increase in referrals to our service (both self-referrals and referrals from professionals). See Outreach to adolescents with symptoms of Bulimia Nervosa: Increasing Accessibility of Treatment project summary for further details.

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We are auditing the case files of all young people treated for BN and EDNOS-BN within the service since MFT-BN was instigated in the service in order to ascertain 1) What proportion of young people receive MFT-BN?, 2) Whether there are features evident at assessment that make referral to MFT-BN more likely; mood (MFQ), anxiety (SCARED and CHOCI), self-harm (DAWBA), severity of eating disorder (EDEQ scores and self-report of binge/purge frequency), family involvement (treated initially alone or with family, assessed alone or with family)? And 3) Whether MFT-BN makes a measureable difference to treatment outcome in comparison to CBT-ED and FT-BN; length of treatment, frequency/intensity of other treatment sessions, eating disorder symptoms at discharge (EDEQ scores and self-report of binge/purge frequency), additional treatment in other services needed at discharge from CAEDS? Phase 2: Pathway development

This phase will consist of treatment evaluation alongside detailed neurocognitive assessment in order to test the effectiveness of the treatment pathways. (1) A case series of young people receiving either CBT-ED or MFT-BN will be conducted and the outcomes compared to neurocognitive profiles to provide proof of concept hypothesis that young people presenting with differing bulimic phenotypes will respond differentially to the two treatments. (2) Funding will be sought for a treatment trial in which patients will be allocated to each treatment arm according to bulimic phenotype. This phase will indicate that outcome of treatment is improved through tailoring treatment as hypothesised. Results: MFT-BN data: Preliminary data from young people who have completed the MFT-BN group indicates that it reduces self-reported eating disorder symptoms (EDEQ, F [1, 23] = 17.38, p < .001), emotion regulation difficulties (DERS F [1, 12] = 17.34, p = .001) and symptoms of internalising disorders (RCADS, F [1, 13] = 4.99, p = .04). Focus group data: Online focus groups and surveys with young people with BN facilitated by BEAT (the

eating disorders charity) had two very clear themes. The first was that we need to be more visible and provide more information for young people experiencing symptoms of BN in order for them to seek treatment earlier in the course of the illness. The second was that information about treatment needs to accessible to young people in schools, sports/activity groups, youth advisory and counselling services. Conclusion: This project will provide evidence that will improve treatments for young people with BN, through demonstrating that treatment outcome can be improved by considering the phenotypic presentation of young people rather treating according to a single diagnostic label. Funding: Funding being sought for Phase 2. Publication:

Stewart C, Voulgari S, Eisler I, Hunt K & Simic M. (2015). Multi-family therapy for bulimia nervosa in adolescence. Eating Disorders, 23(4): 345-55.

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Cognitive behavioural therapy for obsessive compulsive disorder with adolescents recovering from anorexia: A case series

Investigators: Dr Jonathan Espie, Dr Catherine Stewart & Dr Anna Konstantellou National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: Many young people with anorexia also experience other mental health problems and ObsessiveCompulsive Disorder (OCD) is relatively common in these young people. There is an evidence-based psychological therapy available for adolescents with OCD (Cognitive Behavioural Therapy â&#x20AC;&#x201C; CBT for OCD), however, it is not known whether young people going through the difficult process of recovering from anorexia can benefit from CBT for OCD. Young people who experience both anorexia and OCD at the same time (or in very close succession) may well be different to the young people without anorexia who took part in the research studies that first evaluated CBT for OCD. Eleven young people recovering from anorexia with OCD were eligible for a single-case design study. Seven of these completed CBT for OCD. Improvement was measured using a validated semistructured interview and six of seven young people made significant improvements in their OCD problems. State of Progress: Completed Abstract: Background: Young people with anorexia nervosa (AN) commonly have co-existing difficulties such as ObsessiveCompulsive Disorder (OCD). There is increasing recognition that co-existing psychological problems including OCD are often best treated within the specialist teams that treat the eating disorder. However, evidence for the effectiveness of OCD treatment in this context is scant. Moreover, there is evidence that young people who are underweight have significantly worse CBT outcomes compared to controls with OCD with a healthy weight. Therefore, we wished to explore whether CBT for OCD is effective or contra-indicated in young people recovering from AN. Methods: In order to begin gathering evidence, a single case series design was used. Young people with a diagnosis of anorexia (or restrictive EDNOS) and OCD were eligible to take part when they had achieved a healthy weight (or were judged by their therapist to be on course for this over coming weeks), also there was an expectation that Family Therapy for Anorexia (FT-AN) would have progressed to a phase involving increased responsibility for eating enough, with some independence. Eleven young (under 18) people were eligible and entered the study and seven of these young people received Cognitive Behavioural Therapy (CBT) for OCD. The primary measure of change was the Childrenâ&#x20AC;&#x2122;s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), a well validated measure administrated in a semi-structured interview. Results: Six of seven cases showed a statistically improvement in CY-BOCS scores using the Reliable Change Index. No-one who completed treatment experienced deterioration in weight or self-reported eating disorder symptoms (assessed by therapist report, weight chart inspection, and inspection of scores on Eating Disorder Examination Questionnaire). 120

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Conclusion: CBT for OCD appears to have been beneficial at a late stage in the treatment for anorexia (FT-AN), for young people experiencing comorbid OCD. One young person with a diagnosis of Eating Disorder Not Otherwise Specified did not report positive changes in OCD symptoms when assessed with the CY-BOCS. This young person did not have a history of low weight and had psychosis-like experiences at the end of CBT, so was unusual. It does not appear that there are contra indicators for CBT for OCD in this particular group of young people, who have had eating disorder treatment and were of a healthy weight (or approaching a healthy weight) when commencing OCD treatment. Funding: N/A Publications: Pending Figure 11. Difference in CY-BOCS before and after CBT for OCD.

Abbreviation. CY-BOCS = Childrenâ&#x20AC;&#x2122;s Yale-Brown Obsessive-Compulsive Scale, CBT = Cognitive behavioural therapy, OCD = Obsessive-compulsive disorder

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Attachment and mentalisation as predictors of outcome in family therapy for adolescent anorexia nervosa

Investigators: Tom Jewell1, Prof Ivan Eisler2 & Prof Peter Fonagy3 1 Section of Family Therapy, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust; 3 Division of Psychology and Language Sciences, University College London

Lay Summary: Family therapy for adolescent anorexia nervosa is an effective evidence-based treatment but 20-30% do not respond well and have a poor outcome. Emerging evidence suggests that attachment (the nature of relationships with close others, particularly parents and children) and mentalisation (the ability to understand behaviour in terms of mental states such as intentions) may be relevant to treatment outcome. This study will evaluate the specific role that attachment and mentalisation plays in family therapy for adolescent anorexia. This study will help services to identify at assessment those families at risk of poor outcome, and inform new adaptations to treatment. State of Progress: Ongoing Abstract: Background: Family therapy is an evidence-based intervention for adolescent anorexia nervosa (AN). Whilst it is successful in the majority of cases, there remains a sub-group for whom outcomes are poor. Currently, the variables associated with treatment outcome are poorly understood. Emerging evidence suggests that attachment and mentalisation may influence treatment outcomes. This study is the first to investigate attachment and mentalisation as predictors of treatment outcome in adolescents receiving family therapy for AN. Methods: The main study is a prospective observational study of adolescents with AN and their parents recruited as they start family therapy. Data is being collected at three sites, including the Child and Adolescent Eating Disorder service at the SLaM. All consecutive cases referred within the data collection period that are eligible are invited to participate. Self-report measures of attachment, mentalisation, emotion regulation and therapeutic alliance are completed by adolescent patients and parents at the following intervals: assessment, 1 month, 3 months, 6 months and 9 months. The primary outcome is categorical treatment outcome, using the Morgan-Russell scales (Morgan & Russell, 1975). Logistic regression and multi-level modelling will be used to test the theoretical model proposed. Preliminary results: Data collection is ongoing, and the main research questions have yet to be analysed. A preliminary analysis (n=80) found that parentsâ&#x20AC;&#x2122; self-reported therapeutic alliance was predicted by parental mentalising at baseline. Young peopleâ&#x20AC;&#x2122;s therapeutic alliance was predicted by emotion regulation difficulties. Funding: NIHR

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Publications: 1.

Jewell T, Collyer H, Gardner T, Tchanturia K, Simic M, Fonagy, P & Eisler I. (2016). Attachment and mentalization and their association with child and adolescent eating pathology: A systematic review. International Journal of Eating Disorders, 49:354â&#x20AC;&#x201C;373. Jewell T, Blessitt E, Stewart C, Simic M & Eisler I. (2016). Family therapy for child and adolescent eating disorders: A critical review. Family Process, 55(3):577-594.

Pathways in mental health care following treatment of eating disorders in childhood and adolescence

Investigators: Dr Jessica McClelland1, Dr Catherine Stewart1, Dr Antonia Koskina1, Prof Ulrike Schmidt2, Danielle Glennon1 & Dr Mima Simic1 1 National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust; 2 Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: Eating disorders are considered to be more treatable in young people than adults. However, little is known about the pathways taken by young people following discharge from child and adolescent services. This project seeks to examine these pathways and factors predicting them in order to inform service development, personalised care and future research. State of Progress: Ongoing Abstract: Background: Evidence suggests that the response to eating disorder (ED) treatment is more favourable in young people compared to adults, when EDs can become chronic and treatment-resistant. Currently, ED services within the NHS are split into child and adolescent (CAEDS), and adult ED services (e.g. defined by the age of 18 years). This service structure has impeded our understanding of the course of EDs following treatment in childhood/adolescence and factors that predict care pathways in adulthood. This project aims to examine pathways following treatment in CAEDS and factors predicting them. The specific aims of this project are (1) to delineate pathways taken following discharge from CAEDS (e.g. brief/extended treatment in adult ED service, ED/other psychiatric inpatient admissions, use of other mental health services), (2) to calculate the proportion of young people following each of these pathways and (3) to identify features of presentation in CAEDS that are predictive of pathways taken in adult services. Methods: We carried out an audit of young people seen in the CAEDS at South London and Maudsley NHS Foundation Trust over a five-year period. The following data were extracted: i) demographic (e.g. age, ethnicity, gender, parents marital status) ii) national use of mental health services pre and post-18 years of age (e.g. type, number and duration of treatment) and iii) clinical information (e.g. weight, height, ED and comorbidity outcome measures). Results: Data analysis is ongoing.

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Conclusion: This project is currently in the stage of data analysis. We anticipate that the findings from this study will increase our understanding of the course of EDs and service provision following treatment in CAEDS, as well as factors that may be predictive of these pathways. This will contribute to service development (e.g. consideration of transitions between child and adult ED services) as well as future research (e.g. regarding features of presentation in CAEDS that may be predictive of ED chronicity). Funding: This project is being completed in partial fulfilment of a Doctorate in Clinical Psychology. Publication: Pending

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The assessment and management of children in need of inpatient input presenting with psychotic symptoms

Investigators: Nefeli Anagnostopoulou1, Dr Anca Alba1, Dr Jorge Gaete1,2, Dr Danai Dima3,4 & Dr Marinos Kyriakopoulos1,5 1 National & Specialist Acorn Lodge Inpatient Children's Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Public Health and Epidemiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile; 3 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 4 Department of Psychology, School of Arts and Social Sciences, City, University of London; 5 Department of Child and Adolescent Psychiatry, IoPPN, KCL.

Lay Summary: Psychotic symptoms including unusual experiences and beliefs are considered very significant in making the diagnosis of psychotic disorders. However, they are also very commonly experienced by children without any mental health difficulties or by children who present with other conditions. There is very limited research on how common psychotic symptoms are in young children receiving treatment for mental health difficulties. In this project, we explored how frequently children admitted in a mental health inpatient unit present with psychotic symptoms. We also investigated the relationship of these symptoms with the children’s diagnoses and are going to look into these symptoms’ clinical significance. We included all children admitted to our unit over an 8-year period. We found that regardless of their diagnoses, more than 60% children admitted to our unit were experiencing psychotic symptoms. All children with psychotic disorders were experiencing psychotic symptoms as expected. We will further explore whether psychotic symptoms are related with the children’s progress, functioning at discharge, and length of their admission. State of Progress: Ongoing Abstract: Background: Psychotic symptoms, marking impaired reality testing, are considered a hallmark of psychotic disorders. However, several lines of research point towards these symptoms also being highly prevalent both in non-clinical populations and in other psychiatric disorders. There is also evidence to suggest that their prevalence is even higher in children and young people, reaching up to 17% in epidemiological samples. There is limited research on the prevalence of psychotic symptoms in young clinical populations. The present study aimed to assess the prevalence of psychotic symptoms in a 6-12-year-old clinical population of an inpatient setting and their possible association with different diagnoses and clinical outcomes. Methods: Clinical records of all patients of a national UK children’s unit from 2009 to 2017 were examined for the presence of psychotic symptoms and their relationship to diagnosis at discharge, functional outcomes, and children’s and parents’/carers’ satisfaction with treatment. Results: One hundred and eighty-five children were included in the study. Psychotic symptoms were highly prevalent in this young clinical population, reaching 63.8%, regardless of diagnosis at discharge. Hallucinations (58.4%) were more prevalent than delusions (35.1%). As expected, all children with

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schizophrenia spectrum disorders experienced psychotic symptoms. Further analysis of functional outcomes and satisfaction measures is ongoing. Conclusion: The present study is the first to examine the prevalence of delusions and hallucinations across diagnoses in children needing inpatient care. Psychotic symptoms were very common in children without a diagnosis of schizophrenia spectrum disorder. Given the high frequency of psychotic symptoms in this severely affected clinical population, it is possible that they represent a marker of clinical severity which is further explored at present. Funding: N/A Publication:

Anagnostopoulou N, Alba A, Gaete J, Dima D & Kyriakopoulos M. (2018). Prevalence of psychotic symptoms in children needing inpatient care: Relationship to diagnosis. European Psychiatry, 48: S699-700.

What was helpful questionnaire (WHQ): Psychometric properties of a novel tool designed to capture parental perceived helpfulness of interventions in children requiring mental health inpatient care

Investigators: Ifigeneia Mourelatou1, Dr Jorge Gaete1,2, Sandra Fewings1, Oona Hickie1 & Marinos Kyriakopoulos1,3 1 National & Specialist Acorn Lodge Inpatient Children's Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Public Health and Epidemiology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile; 3 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: Children in inpatient mental health care require several treatment approaches, including behavioural management, psychological and family interventions and, commonly, medication. The combination and relative contributions of different approaches and parental perception of how helpful they are has not been studied. Given that there is not a well-studied tool to assess perceived helpfulness of this combination of interventions in inpatient care for children, we aimed to validate the What was Helpful Questionnaire (WHQ) we use on Acorn Lodge, the SLAM Children’s Inpatient Unit, as part of a wider evaluation of our service. The WHQ is a short questionnaire on aspects of interventions that parents may have found helpful in their child’s care. We planned to look at this feedback and explore whether overall parental and child satisfaction with the service, some demographic and clinical characteristics and outcome measures were associated with parental reports of the helpfulness of this combination of interventions. We found that the WHQ is a very good measure of perceived helpfulness by the parents of children admitted to our unit and seemed to be related to overall satisfaction with our service. State of Progress: Completed

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Abstract: Background: Children in mental health inpatient care require multidimensional treatment, including behavioural management, psychological and family interventions and, commonly, medication. So far, there is not a comprehensive instrument to assess perceived helpfulness of this combination of interventions in inpatient care for children. The What was Helpful Questionnaire (WHQ) is a tool designed to capture parental perceived helpfulness of the multidimensional management approach used in these settings. Methods: All 73 inpatients discharged from Acorn Lodge from December 2013 to December 2016 were included in this project. The psychometric properties of WHQ were examined with the use of correlations with outcome and satisfaction measures and exploratory factor analysis using polychoric correlations was conducted. Results: A total of 52 parents or carers (71%) had completed all or part of WHQ. The factor analysis identified one latent factor, and the internal consistency was good. A strong relationship between the WHQ total score and parental service satisfaction total score was found. Conclusion: Results added evidence for the validity and reliability of the WHQ to measure parental perceived helpfulness of the multidimensional intervention offered in inpatient children’s units. Administration of WHQ in larger independent samples will confirm the generalisability of these findings and help clarify the relative contribution of specific aspects of care in perceived parental helpfulness. Funding: N/A Publications: Submitted for publication - under review.

Clinical correlates of comorbid chronic tics and Tourette syndrome in a national inpatient children’s unit

Investigators: Dr Shaheen Zinna 1 & Dr Marinos Kyriakopoulos1,2,3 1 National & Specialist Acorn Lodge Children's Inpatient Unit, South London and Maudsley NHS Foundation Trust; 2 Tourette Syndrome Clinic, Great Ormond Street Hospital for Children, London; 3 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: Children in need of admission to an inpatient mental health unit often present with mixed neuropsychiatric disorders. Among the symptoms of these challenging conditions, admitted children occasionally present with tics. Tics can be motor, i.e. repetitive, involuntary, jerky movements, or vocal, i.e. repetitive, involuntary vocalisations. Their severity can range from mild, occurring without much apparent consequence to the child’s overall presentation, to severe, affecting all aspects of their functioning, and requiring specific interventions in their own right. In mixed neurodevelopmental

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presentations, however, tics, especially when mild in intensity, may not always be considered as a significant factor in the decision-making process on the childâ&#x20AC;&#x2122;s treatment and overall management. In this project, we explored the frequency and clinical importance of chronic tics (i.e. tics which were present for more than a year without significant tic-free periods) and Tourette Syndrome (TS, i.e. a combination of chronic motor and vocal tics). We found that chronic tics and TS were present in almost 1 out of 5 children admitted to our unit which is much more common compared to the general population. The most common comorbid conditions were autism spectrum disorders and obsessivecompulsive disorder (OCD). Children with chronic tics and TS were also more likely to have learning disability and neurodevelopmental problems in their siblings, to take medication at discharge from our unit and to have longer admissions compared to children without tics. This may mean that chronic tics and TS are associated with more severe neurodevelopmental presentations. State of Progress: Completed Abstract: Background: Chronic tics and Tourette syndrome (TS) can be comorbid with several neuropsychiatric conditions and may add to the complexity of childrenâ&#x20AC;&#x2122;s clinical presentation and need for inpatient input. Methods: A retrospective naturalistic study of all patients admitted to our unit from 2009 to 2014 was conducted. Children with and without chronic tics/TS were compared in terms of age, gender, family history of mental illness, history of neurodevelopmental problems in siblings, medication on admission and at discharge, length of admission and functional outcomes using Chi square and t-tests for categorical and continuous data respectively. Results: A total of 133 children (mean age = 11.2 years) were included. Twenty-five (18.8%) were diagnosed with chronic tics/TS. Autism spectrum disorder was the most commonly comorbid diagnosis (84%), with the second most common being an anxiety disorder/OCD (52%). Statistically significant higher percentages of learning disability, neurodevelopmental problems in siblings, medication at discharge and longer inpatient admissions were identified in children with tics compared with the rest of the sample. No other differences were found. Conclusion: The prevalence of chronic tics/TS in children needing inpatient treatment is significant. In our sample, chronic tics/TS seem to represent a marker of increased neurodevelopmental deviance and overall symptom severity. Funding: N/A Publication:

Zinna S & Kyriakopoulos M. (2016). Clinical correlates of comorbid chronic tics and Tourette syndrome in a national inpatient children's unit. European Psychiatry, 33, S137

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Emergency mental health admissions for children: A naturalistic study

Investigators: Dr Marinos Kyriakopoulos1,2, Dr Dennis Ougrin2,3, Carmel Fraser1, Gillene Thomas1 & Rachel McMahon1,4 1 National & Specialist Acorn Lodge Inpatient Children’s Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 National & Specialist Supported Discharge Service, South London and Maudsley NHS Foundation Trust; 4 Pediatric BRAIN Center, University of Illinois at Chicago, USA.

Lay Summary: Only very few children’s inpatient mental health units exist in the National Health Service, for children with the most complex mental health difficulties. These units provide intensive assessment and treatment, including specialist schooling, and have been shown to have a major positive impact on young people and their families. There is no general agreement by Child and Adolescent Mental Health Services (CAMHS) funders or service providers on the need for emergency mental health admission in childhood. Acorn Lodge is one of these children’s units which have been able to offer emergency admissions. In order to evaluate the appropriateness, effectiveness and safety of these admissions, we conducted a project comparing the characteristics, progress and outcomes of children admitted as emergencies with those children admitted following a pre-admission assessment. We also compared parents’/carers’ and children’s satisfaction with the input they received. We found that children admitted as emergencies were not different in terms of their clinical characteristics and progress with the exception of having been more affected by their mental health difficulties on admission and not having been out of school for as long. Parents were more satisfied with emergency compared to planned admissions. We concluded that emergency admissions are appropriate and effective. State of Progress: Completed Abstract: Background: Emergency mental health admissions (EA) for children under 13 years are not routinely offered in the UK, which may be related to preconceptions about their safety, appropriateness and acceptability. Our aim was to evaluate routinely offered EA of children in a national unit over a three-year period. Methods: A retrospective, naturalistic study was conducted, comparing EA with planned admissions (PA) in terms of children’s functioning on admission and discharge, clinical characteristics, significant riskrelated incidents and parental and children satisfaction. Results: EA children (N=47) did not differ from PA children (N=35) in age, length of admission, medication treatment, significant risk-related incidents, functioning at discharge, access to education at discharge and satisfaction. EA children had lower functioning and were less likely to have been out of education on admission. Parental satisfaction in EA was higher compared to PA.

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Conclusion: EA for children are an appropriate, clinically indicated and safe alternative to PA, associated with higher parental satisfaction. Funding: No funding was received. Publication:

Kyriakopoulos M, Ougrin D, Fraser C, Thomas G & McMahon R. (2015). Emergency mental health admissions for children: A naturalistic study. Clinical Child Psychology and Psychiatry, 20(1):8-19.

Measuring stigma in children receiving mental health treatment: Validation of the paediatric selfstigmatization scale (PaedS)

Investigators: Dr Anya Kaushik1, Dr Efstathios Papachristou2, Dr Danai Dima3,4,5, Sandra Fewings1, Evgenia Kostaki1, Prof George B. Ploubidis6 & Dr Marinos Kyriakopoulos1,5,7 1 National & Specialist Acorn Lodge Inpatient Children Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Primary Care & Population Health, University College London; 3 Department of Psychology, School of Arts and Social Sciences, City, University of London; 4 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 5 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; 6 Centre for Longitudinal Studies, Department of Social Science, University College London; 7 Department of Child and Adolescent Psychiatry, IoPPN, KCL.

Lay Summary: Whilst significant work is being done to understand the role of stigma amongst adults needing mental health support, the role of stigma in children with mental health needs is not as well explored. Children’s age affects their understanding of their difficulties and the support they may require. As a result, the research findings about stigma related to mental health treatment in children may not be identical to those identified in adult studies. In order to effectively address the impact of stigma in the lives of children with mental health needs, we must first be able to identify the extent and manifestations of stigma in this younger group. The assessment of stigma will require tools that can reliably measure different aspects of it. In this study, we validated the first scale measuring self-stigmatisation in children aged 8 – 12 years. It is made of 4 subscales assessing societal devaluation (i.e. other children’s/people’s negative attitudes towards a child receiving treatment for mental health difficulties), personal rejection (i.e. other children/people rejecting the child receiving treatment for mental health difficulties), self-stigma (i.e. the child’s own negative feelings about themselves related to the fact they are receiving treatment for mental health difficulties), and secrecy (i.e. the child not revealing the fact they are receiving treatment for mental health difficulties). We hope that this scale will contribute towards a better understanding and reduction of stigma in children receiving treatment for mental health difficulties. State of Progress: Completed

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Abstract: Background: Research on the impact of stigma associated with mental illness in children is scarce. Considering the known negative effects of stigma associated with mental illness in adults, it is crucial to explore the stigma experienced by children who access mental health treatment. However, no scale measuring selfstigmatisation in younger children is available to date. This study aimed to develop and validate such a scale, the Paediatric self-Stigmatization scale (PaedS). Methods: A total of 156 children (119 receiving outpatient and 37 receiving inpatient treatment), aged 8 – 12 years, completed the PaedS, the Self-Perception Profile for Children and the Pediatric Quality of Life Inventory (PedsQL - Child Report, ages 8 – 12). In addition, parents completed the PedsQL (Parent Report for Children, ages 8 – 12), the Strengths and Difficulties Questionnaire (SDQ) and a modified subscale of the PaedS measuring the children’s rejection by others due to their mental health difficulties. Results: A confirmatory factor analysis showed that a four-factor structure, comprising Societal Devaluation, Personal Rejection, Self-Stigma and Secrecy scales, had excellent fit to the data (CFI=0.95; TLI=0.95; RMSEA=0.05). Child-reported PaedS scores were positively correlated with parental-reported PaedS scores and negatively with PedsQL, the SDQ, and 5 out of 6 sub-scales of the Self-Perception Profile for Children, suggesting adequate convergent validity (all p-values<0.05). Conclusion: The PaedS is a valid instrument which is hoped to advance the understanding of self-stigmatisation in children with mental health difficulties and contribute to its prevention. Funding: Maudsley Charity Publication:

Kaushik A, Papachristou E, Dima D, Fewings S, Kostaki E, Ploubidis G & Kyriakopoulos M. (2017). Measuring stigma in children receiving mental health treatment: Validation of the Paediatric Self-Stigmatization Scale (PaedS). European Psychiatry, 43:1-8

Hospital admission for severe paediatric dissociative disorder

Investigators: Dr Matthew Rinaldi1, Dr Daniel Ilzarbe2,3 & Dr Marinos Kyriakopoulos1,2,4 1 National & Specialist Acorn Lodge Inpatient Children Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic de Barcelona 4 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

Lay Summary: There are a range of conditions that cause children to display apparently neurological symptoms

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(blindness, paralysis, seizures, fainting) but cannot be explained by any known medical condition. These are referred to as dissociative disorders and are related to significant mental health problems. It is a rare condition, but these patients prove challenging for clinicians to treat, particularly because there is a lack of research in children with this disorder. Often, they will be admitted to hospital because the symptoms can cause difficulties in the child’s personal, family and school life. We looked at all children who were admitted to a national inpatient unit for under-12-year-olds. We found eight children who were admitted and treated for dissociative disorders. When we compared their characteristics, outcomes and satisfaction with their treatment with all the other children who were admitted we found a few important results. Firstly, all the children, although complicated with multiple diagnoses, improved during their inpatient admission. However, dissociative disorders naturally improve with time, so we cannot completely say that this was due to the admission alone. We also found that they spent on average 53 more days on the ward than other children. Finally, parents were less satisfied about professionals’ ability to listen to worries they may have about their child. This is important for children, families and staff to know that children with dissociative disorders tend to improve with inpatient admission but could expect to stay in hospital for slightly longer than average and may be less satisfied with their interactions with professionals. State of Progress: Completed Abstract: Background and Methods: Though children with dissociative disorders (DD) are referred to mental health inpatient units, no research exists to endorse this. We studied the outcomes of patients with DD over a 5-year period on a national inpatient unit for children up to 12 years of age. Demographic, clinical and satisfaction data was collected and compared with other inpatients not having DD. Results: Eight patients were identified, of whom six were female. All had several comorbidities. Mean Children’s Global Assessment Scale (CGAS) scores improved from admission to discharge from 31 to 61. Admissions in DD were longer by 53 days (p=0.059) and parents were statistically less satisfied about professionals’ ability to listen to worries they may have about their child (p=0.049). Conclusion: Referrers should expect children with DD to respond as well to inpatient interventions as those with other diagnoses but potentially with marginally longer admissions and lower parental satisfaction. Funding: N/A Publications: Submitted to Clinical Child Psychology and Psychiatry – awaiting peer review

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Table 1. Demographic characteristics and clinical outcomes of children with dissociative disorder admitted in a mental health inpatient setting

Table 2. Acorn Satisfaction Questionnaire rated by parents and children admitted to a mental health unit over a period of 5 years

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Determination of psychosis-related clinical profiles in children with autism spectrum disorders using latent class analysis

Investigators: Dr Marinos Kyriakopoulos1,2,3, Dr Argyris Stringaris4, Dr Sofia Manolesou5, Dr Maja Drobnič Radobuljac6, Dr Brian Jacobs1, Prof Avi Reichenberg3, Dr Daniel Stahl7, Prof Emily Simonoff1, 2 , & Prof Sophia Frangou3 1 Child and Adolescent Mental Health Clinical Academic Group, South London and the Maudsley NHS Foundation Trust; 2 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 3 Icahn School of Medicine at Mount Sinai, New York, USA; 4 Mood and Brain Development Unit, National Institute of Mental Health, Bethesda, USA; 5 Central and North West London NHS Foundation Trust, London; 6 University Psychiatric Hospital, Ljubljana, Slovenia; 7 Department of Biostatistics and Health Informatics, IoPPN, KCL.

Lay Summary: Autistic and psychotic disorders have historically been considered as related conditions. For several decades, they have been split into separate diagnostic categories but their boundaries continue to be debated. Better understanding of psychosis-related symptom profiles in children with autism spectrum disorders (ASD) is likely to help in our understanding of overlapping and distinct characteristics of these conditions. We examined all children with ASD without a psychosis diagnosis admitted on Acorn Lodge, the SLAM Children’s Inpatient Unit, over a 9-year period. We looked for symptoms of emotional dysregulation and anxiety, social communication difficulties, and thought disorder symptoms which are closer to psychosis. We used a statistical method to explore if on the basis of the symptoms children experienced, they could be classified into different subgroups. We found that children with ASD could be categorised in two groups depending on the presence or absence of psychotic features. The group of children with ASD and psychotic features had longer admissions compared to those without. We concluded that this classification may be a promising way forward in understanding the clinical significance of psychotic symptoms in ASD. State of Progress: Completed Abstract: Background: In children with autism spectrum disorders (ASD), high rates of idiosyncratic fears and anxiety reactions and thought disorder are thought to increase the risk of psychosis. The critical next step is to identify whether combinations of these symptoms can be used to categorise individual patients into ASD subclasses, and to test their relevance to psychosis. Methods: All patients with ASD (n=84) admitted to a specialist national inpatient unit from 2003 to 2012 were rated for the presence or absence of impairment in affective regulation and anxiety (peculiar phobias, panic episodes, explosive reactions to anxiety), social deficits (social disinterest, avoidance or withdrawal and abnormal attachment) and thought disorder (disorganised or illogical thinking, bizarre fantasies, overvalued or delusional ideas). Latent class analysis of individual symptoms was conducted to identify ASD classes. External validation of these classes was performed using as a criterion the presence of hallucinations.

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Results: Latent class analysis identified two distinct classes. Bizarre fears and anxiety reactions and thought disorder symptoms differentiated ASD patients into those with psychotic features (ASD-P; 51%) and those without (ASD-NonP: 49%). Hallucinations were present in 26% of the ASD-P class but only 2.4% of the ASD-NonP. Both the ASD-P and the ASD-NonP class benefited from inpatient treatment although inpatient stay was prolonged in the ASD-P class. Conclusion: This study provides the first empirically-derived classification of ASD in relation to psychosis based on three underlying symptom dimensions, anxiety, social deficits and thought disorder. These results can be further developed by testing the reproducibility and prognostic value of the identified classes. Funding: N/A Publication:

Kyriakopoulos M, Stringaris A, Manolesou S, Radobuljac MD, Jacobs B, Reichenberg A, Stahl D, Simonoff E, Frangou S. (2015). Determination of psychosis-related clinical profiles in children with autism spectrum disorders using latent class analysis. European Child & Adolescent Psychiatry, 24(3):301-7

Predictors of multiple treatment failure of antipsychotics in early onset psychosis

Investigators: Dr Johnny Downs1,2,3, Harry Dean1, Suzannah Lechler1, Nicola Sears1, Dr Rashmi Patel2,4, Hitesh Shetty2, Prof Matthew Hotopf1,2, Prof Emily Simonoff3, Prof Tamsin Ford5, Dr Marinos Kyriakopoulos2,3,6, Dr Covadonga M. Diaz-Caneja7, Dr Celso Arango7, Dr James H. MacCabe2,4, Dr Richard D. Hayes1 & Dr Laura Pina-Camacho3,7 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 NIHR Maudsley Biomedical Research Centre, London, South London and Maudsley NHS Foundation Trust; 3 Department of Child and Adolescent Psychiatry, IoPPN, KCL; 4 Department of Psychosis Studies, IoPPN, KCL & NIHR South London and Maudsley Biomedical Research Centre; 5 University of Exeter Medical School, Exeter; 6 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA; 7 Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM, Madrid, Spain.

Lay Summary: Nearly one in five of people who have severe mental illness like schizophrenia or bipolar disorder will experience the first signs of psychosis before adulthood. Psychosis in young people is similar to adulthood; they will often experience hearing things that are not there (hallucinations) or have trouble from distinguishing reality from their own troubling thoughts (delusions), and often become very confused, and have trouble organising their thoughts. The course of treatment is largely the same too, using a combination of antipsychotic medication and supportive psychological, educational and family therapy for the parents and young person as they recover. The faster the recovery, the greater the chances the young person can get back on track with school or training, and the lower the chances they have of experiencing another episode. However, some young people do not recover so well, and it is not clear which young people may need more support early on in their treatment, rather than wait to find out whether they will recover using the standard treatment. We used a combination of techniques developed by data scientists called natural language processing (NLP) which is a method of rapidly

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searching through clinical documentation. We applied these methods to the electronic health records in SLaM for young people with severe psychotic symptoms who had received CAMHS treatments for several years. These NLP techniques helped us find which symptoms and co-existing problems predicting those who may not respond well to conventional anti-psychotic medications – showing us who may benefit from more intensive supportive therapies early-on in treatment. State of Progress: Completed Abstract: Background: Which background factors and presenting features impact on prognosis is unclear in young people with a first episode of early-onset psychosis (EOP)? Studies in adults suggest the presence of negative symptoms (NS) which include lack of motivation, problems with social interaction or diminished emotional range may be associated with reduced treatment effectiveness. In addition, co-occurring neurodevelopmental problems or family history of psychosis have also been found to be greater in adults with more severe psychotic disorders. In a sample of 638 children with EOP (aged 10–17 y, 51% male), we assessed whether NS, neurodevelopmental problems, and family history of psychosis at first presentation to mental health services predicted eventual development of multiple treatment failure (MTF) prior to the age of 18 (defined by initiation of a third trial of novel antipsychotic due to prior insufficient response, intolerable adverse-effects or non-adherence). Methods: Data were extracted from the electronic health records held by child inpatient and community-based services in South London, United Kingdom. Natural Language Processing tools were used to measure the presence of Marder Factor NS, Family history of psychosis, co-morbid neurodevelopmental disorders and patterns of antipsychotic use. Results: The association between presenting with ≥2 NS and the development of MTF over a 5-year period was modeled using Cox regression. Out of the 638 children, 37.5% showed ≥2 NS at first presentation, and 124 (19.3%) developed MTF prior to the age of 18. The presence of NS at first episode was significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07–2.46; P = .02) after controlling for a number of potential confounders including psychosis diagnostic classification, positive symptoms, comorbid depression, and family history of psychosis. Black ethnicity (aHR 1.78, 95% CI: 1.11–2.87; P = .02), older age at first presentation (aHR 1.27, 95% CI: 1.109–1.49; P = .002), comorbid diagnosis of Autism Spectrum Disorders (aHR 1.70, 95% CI: 1.03–2.79; P = .04), and first degree relative with psychotic disorder (aHR 2.11, 95% CI: 1.35–3.30; P = .001) were also significantly associated with MTF. Conclusion: There is a high prevalence of NS in EOP around patients’ first presentation to services and across psychosis diagnosis classifications. Black ethnicity and the presence of NS, ASD, and family history of psychosis, around the first stages of the illness identify a subset of children and adolescents who may be at higher risk of responding poorly to antipsychotics, both through refractory symptoms and high sensitivity to side-effects. Optimisation of current pharmacological and non-pharmacological strategies for these patients, and further research involving agents that better target NS are warranted. Funding: Medical Research Council, Psychiatry Research Trust Peggy Pollak Fellowship, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. 137

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Publications: 1.

Downs J, Dean H, Lechler S, Sears N, Patel R, Shetty H, Hotopf M, Ford T, DiazCaneja MD, Arango C, McCabe JH, Hayes RD & Pina-Camacho L. (2018). Negative symptoms in early-onset psychosis and their association with antipsychotic treatment failure, Schizophrenia Bulletin, doi: 10.1093/schbul/sbx197 Downs J, Lechler S, Dean H, Sears N, Patel R, Shetty H, Simonoff E, Hotopf M, Ford T, Diaz-Caneja MD, Arango C, McCabe JH, Hayes RD & Pina-Camacho L. (2017). The association between co-morbid autism spectrum disorders and antipsychotic treatment failure in early- onset psychosis: A historical cohort study using electronic health records. Journal of Clinical Psychiatry, 78(9):e1233-41, doi: 10.4088/JCP.16m11422

Disparities in detention: An investigation into relationships between sociodemographic status and compulsory psychiatric care among children and adolescents

Investigators: Dr Susan Walker1, Dr Johnny Downs2,3, Dr Richard Hayes4, Prof David Skuse1 & Prof Sonia Johnson1 1 Division of Psychiatry, University College London; 2 South London and Maudsley NHS Foundation Trust; 3 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 4 Department of Psychological Medicine, IoPPN, KCL.

Lay Summary: The aim of this research is to understand more about the children and young people admitted to psychiatric hospitals against their will. This is important as we need to know which young people are most at risk of having this happen and why, in order to start to work out what we can do to reduce these admissions. This study is the first large scale investigation into the compulsory admission of children and adolescents. It will be carried out in two phases. In the first phase will use the largest database of its kind which links SLaM NHS Child and Adolescent Mental Health Service (CAMHS) records to the national schools database held by the Department for Education. This will enable an examination of the links between the characteristics of children and young people and the likelihood of them being compulsorily detained. We will talk to adolescents who have been detained, their parents/ guardians and people who work in the NHS. We will find out what they think about compulsory care, their experiences, and their understanding of why they were detained. State of Progress: Future Abstract: Background: The number of people, including children and adolescents, being detained in psychiatric units under the Mental Health Act 1983 (MHA) is growing. This has become a high-profile issue as compulsory care contradicts the ethos of modern medical ethics, can be associated with poor long-term mental health outcomes, and diverts significant funds from community services. It has been identified as a priority for urgent change by the Care Quality Commission (CQC), and there is an imperative to reduce the rate of detentions through early community intervention, targeted at those groups most at risk of detention. While inequalities in use of the MHA are well documented in adults, we know very little about the factors that may increase the risk of detention among children and adolescents.

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Understanding the disparities in risk and experiences of compulsory admission among children and adolescents is needed in order to identify modifiable causes and highlight where preventative interventions should be targeted. Aim: To undertake a linked quantitative and qualitative investigation of disparities in risk and experiences of compulsory psychiatric care among children and adolescents, in order to identify modifiable causes and expose potential targets for preventative intervention. Methods: This study is a two-phase mixed-methods sequential explanatory design. Phase 1: Quantitative

The world’s largest database of child and adolescent mental health service (CAMHS) records that can be used for research purposes, the Clinical Record Interactive Search system (CRIS) established by Kings College London and South London and the Maudsley NHS Trust (SLaM) has recently been linked to the National Pupil database (NPD). This highly novel UK linked dataset will be exploited to identify young people aged 10-17 detained under the MHA over an 8-year period from the population of four boroughs in South London (over 155,000 young people). The in-depth clinical information within CRIS linked with the census data within the NPD will enable modelling of the associations between individual-level sociodemographic factors (e.g. ethnicity and looked-after-child status), clinical factors (e.g. diagnosis, previous treatment) and risk of a compulsory admission. Phase 2: Qualitative

Building on the findings from phase 1, the views and experiences of key stakeholders will be sought to explore factors underlying the reasons for their detention. Semi-structured interviews will be carried out with 20 adolescents who have been detained and ten of their parents/guardians. Purposive sampling will be used to ensure to offer demographic and phenomenal variation, led by the findings of Phase 1, and interviews will be flexible but cover perceptions of the detention, circumstances leading to it, experience of the MHA assessment and inpatient care. The interviews will be analysed using thematic analysis. The views of healthcare professionals involved in decisions to detain children and adolescents will be sought through two focus groups. Summary of potential benefits to patients and the NHS: This research will identify any disparities in the use of the MHA in young people, which could be contributing to life-long inequalities of access to mental health services, and repeated compulsory admissions among certain groups. It will be the UK’s first large scale investigation into the compulsory care of minors, and the first time that the combined narratives of young people who have been detained, their parents/guardians and healthcare professionals will have been heard and used to explore experiences of detention and pathways to care. Improving our understanding of young people’s risks and experiences of detention will provide an evidence-base to inform service improvement, address staff training and support needs, and guide the implementation of targeted community support to reduce the need for coercive inpatient care. This will offer obvious benefits to the NHS, including significant economic savings. Funding: NIHR Clinical Doctoral Fellowship (SW); the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (J.D, R.H). Psychiatry Research Trust Peggy Pollak Fellowship (J.D); NIHR Mental Health Policy Research Unit (J.D, S.J)

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The role of ethnicity and diagnosis in rates of adolescent psychiatric admission and compulsory detention: A longitudinal case-note study

Investigators: Dr Richard Corrigall1 & Prof Dinesh Bhugra2 1Snowsfields Adolescent Unit, South London and Maudsley NHS Foundation Trust; 2 Department of Health Service and Population Research, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

State of Progress: Completed Abstract: Background: There is substantial evidence of ethnic variation in psychiatric admission and use of the Mental Health Act among adults in the UK. The findings have been reflected in a census of the ethnicity of psychiatric inpatients in England and Wales, showing higher than average rates of admission among some minority ethnic groups, especially Black and White/Black mixed groups and higher than average rates of detention among Black, White/Black Caribbean Mixed and Other White Groups. The census data did not, however, show an increased rate of detention for Asian groups. Only one previous study has addressed ethnic variation in psychiatric admission among adolescents. Prevalence according to ethnicity was reported for all diagnostic groups, but an analysis of the risk of admission according to ethnic population and comparisons between ethnic groups in the use of detention was limited to cases of psychosis. In this study, a longitudinal sample has been taken from the clinical database of an adolescent unit in South London. To investigate variations in admission and in the use of The Mental Health Act, both by diagnosis and by ethnicity and to explore whether ethnic variations in psychiatric admission and reported for adults also apply to adolescents. Methods: This study was a longitudinal, case-note study over a 10-year period set in an adolescent inpatient psychiatric unit in London. The participants were all adolescents admitted to the unit. To obtain sufficient numbers in each group for statistical comparison, ethnic categories were collapsed into the following groups: (1) White, including White British, White Irish, White Other; (2) Black, including Black British, Black Caribbean, Black African, Black Other; (3) Asian, including Indian, Pakistani, Bangladeshi, Asian Other (4) Other, including other ethnic groups and mixed ethnic origins. The main outcome measures were rates of admission and detention under the Mental Health Act, according to catchment area population. ICD-10 diagnoses were simplified into two groups: psychosis and nonpsychosis (predominantly affective and stress-related disorders). Results: Young Black people were nearly six times more likely than the White group to be admitted with psychosis but showed no increase in admission for non-psychotic conditions. Young people in the Other group were over three times more likely to be admitted with psychosis but showed only a modest increase in admission with non-psychotic conditions. Young Asians were over twice as likely to be admitted with psychosis but were only one-third as likely to be admitted with non-psychotic conditions. Young people with psychosis in the Black and Other groups were around three times more likely to have been detained, but there were no significant differences for non-psychotic conditions. Conclusion: Significant ethnic variation was found in the rates of admission and detention for adolescents. However, 140

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diagnosis was also an important consideration and must be taken into account when examining for evidence of ethnic bias in the use of mental health services by young people. Further investigation is required to establish whether adolescent care pathways are providing a safe and appropriate level of inpatient care for all ethnic groups. Funding: N/A Publication:

Corrigall R & Bhugra D. (2013). The role of ethnicity and diagnosis in rates of adolescent psychiatric admission and compulsory detention: A longitudinal case-note study. Journal of the Royal Society of Medicine, 106(5):190-5.

Coping with unusual experiences for 12 to 18 year olds (CUES+). A transdiagnostic randomised controlled trial of the effectiveness of cognitive behaviour therapy in reducing distress associated with unusual experiences in adolescent mental health services

Investigators: Dr Sophie Browning1, Karen Bracegirdle2, Dr Richard Corrigall3 & Dr Suzanne Jolley4 1 Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust; 2 CUES, South London and Maudsley NHS Foundation Trust; 3 Snowsfields Adolescent Unit, South London and Maudsley NHS Foundation Trust; 4 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: Individual and family-based psychological therapies are recommended for young people under 18 years with unusual or psychotic-like experiences that are upsetting or interfere with daily life (UEDs). Therapies aim to reduce current problems, and improve future mental health, but more research is needed to test them in under eighteens. Our study tested whether individual and familybased psychological therapy for UEDs (CBT-UED), added to usual care in Child and Adolescent Community Mental Health Services (CAMHS) improved outcomes for young people with UEDs compared to usual care alone. State of Progress: Awaiting final outcome analyses Abstract: For adults with psychosis, individual and family-based cognitive behavioural therapy (CBTp) is recommended . The same recommendation is made for under eighteens, and childhood presentations of psychotic-like, or unusual experiences accompanied by distress or adverse life impact, but there have thus far not been any child-specific trials. Our study tested whether CBT-UED added to usual care in CAMHS improved outcomes for young people with UEDs compared to usual care alone. We recruited 122 young people with UEDs and trained 30 CAMHS therapists over two years. Feedback from young people, parents and therapists was very positive. Analyses are ongoing but comparing the means between the groups suggests improvements in the CBT-UED group on our main and secondary outcomes, but only a small difference, and no reduction in costs, compared to the control group. 141

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We have shown that screening for UEDs in routine CAMHS is feasible. CBT-UED can be successfully delivered with training and supervision, and may make small improvements to outcomes for young people with UEDs, but at relatively high cost. Further development is therefore needed. Background: Psychosis is a disabling and costly mental health condition with adverse social and functional outcomes, even following an at-risk presentation. For adults with psychosis, individual and familybased cognitive behavioural therapy (CBTp) is recommended . The same recommendation is made for under eighteens, and childhood presentations of psychotic-like, or unusual experiences accompanied by distress or adverse life impact, but based on adult, rather than child-specific trials. Childhood UED prevalence is around 15% in the general population and 50% in CAMHS; UEDs are associated with a range of poor mental health outcomes, indicating intervention to reduce current distress and disability, which may additionally increase resilience and reduce future mental health risk. Trials in children are needed, to build a youth-specific evidence base for early intervention with UEDs: emerging evidence suggests some common psychological targets of therapy but also indicates the need for developmental adaptations to standard protocols. We have previously shown that adapted, child-specific cognitive behavioural interventions targeting adolescent psychosis or childhood UEDs are feasible, acceptable, safe and potentially helpful. We planned a parallel group randomised controlled trial, to test the clinical and cost-effectiveness of our adapted CBT for childhood UEDs (CBT-UED), as an adjunct to routine care in reducing distress in adolescents with UEDs in the context of psychosis or any other presentation, in community CAMHS, compared to TAU alone. Methods: Participants: We recruited young people with UEDs aged 12-18 years from CAMHS in four London boroughs, routinely screened by the borough team in their intake assessment. Design & procedure: Trained research workers completed baseline assessments with consenting parents and

young people prior to randomisation. Treatment as usual (TAU) was delivered without interference in both conditions and included care co-ordination, practical and emotional support for the young person and their family, and medication. Follow-up assessments at 16-weeks (post-therapy) and 24-weeks (2-months post-therapy) were carried out blind to treatment allocation. Service and economic measures were completed for the 6-month periods before and after baseline. After 24-weeks, TAU participants were offered the intervention. Our main outcome was emotional problems at 16 weeks, assessed using the Emotional Problems subscale of the Strengths and Difficulties Questionnaire. Key secondary outcomes were UEDs, risk/adverse events and costs. Therapy: Therapy comprised â&#x2030;¤12 individual sessions and â&#x2030;¤4 family sessions, lasting up to an hour,

usually delivered weekly. Therapy adaptations included: shorter duration of sessions and of therapy as needed; greater emphasis on behavioural change; explicit connection with educational, social, familial, and particularly peer context, and a focus on the developing sense of self and identity. We trained 30 CAMHS therapists over two years, who each saw between one and four therapy cases. The specific research questions to be addressed were: 1) Are clinical outcomes for young people with UEDs improved by the addition of CBT-UED to routine care?; 2) Are the effect sizes comparable to those found in the adult literature?; and 3) Is the intervention cost-effective? Results: Recruitment through routine screening was feasible. We recruited 122 young people. UED prevalence was around 60%. Participants were 76% female; 50% from black or minority ethnic groups; 44% had previous CAMHS contact; mean age 14.25 years. 61 were allocated at random to CBT-UED and 61 to TAU. All but two young people attended at least one session of CBT-UED (range: 1 to 16, mean 9.5 sessions, SD=4.5). No serious adverse events were attributed to participation. Feedback from young

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people, parents and staff/therapists was very positive. Analysis is ongoing but preliminary outcome analyses suggest some improvement for the CUES+ group, but not significantly greater than in the control group, with no cost advantage for the CBT-UED group. Conclusion: This was the first trial of CBT-UED exclusively in under eighteens. Routine screening by teams successfully identified childhood UEDs and delivery by CAMHS therapists was feasible. Therapy was well received, and potentially helpful, but any overall positive effects were small. Further development is therefore needed to improve both clinical and cost- effectiveness. Nevertheless, the services hosting the study are keen to continue to offer the therapy locally, and we are supporting this with ongoing supervision and training to CAMHS and Early Intervention Psychosis services staff. Funding: NIHR Publications: 1.

Gin K, Banerjea P, Abbott C, Browning S, Bracegirdle K, Corrigall R & Jolley S. (2018). Childhood unusual experiences in community child and adolescent mental health services in south east London: Prevalence and impact. Schizophrenia Research, 195:93-96 Jolley S, Browning S, Corrigall R, Laurens KR, Hirsch C, Bracegirdle K, Gin K, Muccio F, Stewart C, Banerjea P, Kuipers E, Garety P, Byrne M, Onwumere J, Achilla E, McCrone P & Emsley R. Coping with Unusual ExperienceS for 12-18 year olds (CUES+): Study protocol for a transdiagnostic randomised controlled trial of the effectiveness of cognitive therapy in reducing distress associated with unusual experiences in adolescent mental health services. Trials, 18:586. doi: 10.1186/s13063-017-2326-4

Comparison of effectiveness and cost-effectiveness of an intensive community supported discharge service versus treatment as usual for adolescents with psychiatric emergencies: a randomised controlled trial

Investigators: Dr Dennis Ougrin1, Dr Richard Corrigall2, Jason Poole2,3, Dr Toby Zundel2, Mandy Sarhane2, Victoria Slater2, Daniel Stahl4, Paula Reavey3, Prof Sarah Byford5, Margaret Heslin5, John Ivens3, Maarten Crommelin3, Zahra Abdulla4, Dr Daniel Hayes3, Kerry Middleton3, Benita Nnadi5 & Prof Eric Taylor1 1 Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Snowsfields Adolescent Unit, South London and Maudsley NHS Foundation Trust; 3 Department of Psychology, London South Bank University; 4 Department of Biostatistics and Health Informatics, IoPPN, KCL; 5 Department of Health Service and Population Research, IoPPN, KCL.

Lay Summary: Intensive community treatment to reduce dependency on adolescent psychiatric inpatient care is recommended in guidelines but has not been assessed in a randomised controlled trial in the UK. We designed a supported discharge service (SDS) provided by an intensive community treatment team and compared outcomes with usual care. The study, a single-blind, patient level, parallel-group randomised controlled study included 106 patients aged between 12 and 18, from the boroughs of Southwark, Lambeth, Croydon, Lewisham and Kent, who were admitted to inpatient units at the Trust, or private inpatient units when units at the Trust were full. Patients were randomly allocated to receive either

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usual in-patient care followed by a return to standard outpatient care, or to be discharged early with intensive community support provided by the SDS, a team offering intensive therapeutic support and access to home treatment, day care and intensive case management. Home treatment is an integral part of community support from the SDS teams, which includes mental state monitoring, administering medication, monitoring of side effects and individualised psychotherapies. SDS aims to engage family members in all aspects of care and also supports young people in their school or vocation and positive recreational activities. Patients in the SDS group were also found to have spent significantly fewer days out of school than the control group and were more likely to reintegrate into an educational setting. The findings from the study also suggest a trend towards reduced bed usage at the 6-month follow up. The trial revealed using intensive community services was associated with clinical improvements similar to inpatient care, in line with studies in other countries. Abstract Background: Approximately 4420 adolescents were admitted to specialist child and adolescent mental health units in England and Wales in 2014. This number is double that of 10 years earlier. The number of children and young people who have presented to accident and emergency departments with a psychiatric disorder has also more than doubled from 8,358 in 2010–11 to 17,278 in 2013–14.3 Although the proportion of young people being admitted is small, the associated disruption can be substantial and long term, and the accompanying demand on health service resources is very high. Most young people admitted to hospital are likely to have a history of self-harm. Urgent psychiatric admissions for adolescents can lead to serious distress, and the highest risks of suicide and self-harm are encountered in the period soon after discharge. Despite these concerns, little is known about the optimum models of care. We designed the supported discharge service versus inpatient care evaluation (SITE) RCT to assess the benefits of an intensive community treatment, termed supported discharge service (SDS), compared with usual care, assessed in terms of hospital inpatient care and changes in symptoms and social functioning, and explored cost-effectiveness. Methods: Eligible patients for this randomised controlled trial were younger than 18 years and had been admitted for psychiatric inpatient care in the South London and Maudsley NHS Foundation Trust. Patients were assigned 1:1 to either the SDS or to usual care by use of a computer-generated pseudorandom code with random permuted blocks of varying sizes. The primary outcome was the number of inpatient bed-days, changes in Strengths and Difficulties Questionnaire (SDQ) scores, and changes in the Children’s Global Assessment Scale (CGAS) scores at 6 months, assessed by intention to treat. Costeffectiveness was explored with acceptability curves based on CGAS scores and quality-adjusted life-years (QALYs) calculated from the three-level EuroQol-5D measure of health-related quality of life (EQ-5D-3L), taking a health and social care perspective. This study is registered with the ISRCTN Registry, number ISRCTN82129964. Results: Hospital use at 6 months was significantly lower in the SDS group than in the usual care group (unadjusted median 34 IQR 17–63 vs 50 days, 19–125, p=0·04). The ratio of mean total inpatient days for usual care to SDS was 1·67 (95% CI 1·02–2·81, p=0·04), which decreased to 1·65 (0·99–2·77, p=0·057) when adjusted for differences in hospital use before randomisation. Scores for SDQ and CGAS did not differ between groups. The cost-effectiveness acceptability curve based on QALYs showed that the probability of SDS being cost effective compared with usual care was around 60% with a willingness-to-pay threshold of £20 000–30 000 per QALY, and that based on CGAS showed at least 58% probability of SDS being cost-effective compared with usual care irrespective of willingness to pay. We recorded no adverse events attributable to SDS or usual care.

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Conclusion: SDS provided by an intensive community treatment team reduced bed usage at 6 monthsâ&#x20AC;&#x2122; follow-up but had no effect on functional status and symptoms of mental health disorders compared with usual care. The possibility of preventing admissions, particularly through features such as reduced self-harm and improved reintegration into school, with intensive community treatment should be investigated in future studies. Funding: South London and Maudsley NHS Trust. Publication:

Ougrin D, Corrigall R, Poole J, Zundel T, Sarhane M, Slater V, Stahl D, Reavey P, Byford S, Heslin M, Ivens J, Crommelin M, Abdulla Z, Hayes D, Middleton K, Nnadi B, Taylor E. (2018). Comparison of effectiveness and cost-effectiveness of an intensive community supported discharge service versus treatment as usual for adolescents with psychiatric emergencies: A randomised controlled trial. Lancet Psychiatry, doi: 10.1016/ S2215-0366(18)30129-9.

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Can a parent-focused intervention reduce emotional and behavioural problems in young children with ASD? The autism spectrum treatment and resilience (ASTAR) feasibility and pilot trial

Investigators: Prof Tony Charman1, Prof Stephen Scott2, Dr Vicky Slonims3, Prof Andrew Pickles4, Prof Bryony Beresford5, Prof Martin Knapp6, Prof Dale Hay7, Dr Melanie Palmer2, Dr Joanne Tarver2, Dr Juan Paris Perez2, Thomas Cawthorne2, Dr Victoria Hallett8, Dr Joanne Mueller8, Dr Lauren Breese8, Dr Megan Hollett8 & Prof Emily Simonoff1. 1 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Child and Adolescent Psychiatry, IoPPN, KCL; 3 Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas NHS Foundation Trust, London; 4 Department of Biostatistics and and Health Informatics, IoPPN, KCL;5 Social Policy Research Unit, University of York; 6 Department of Social Policy, London School of Economics and Political Science; 7 School of Psychology, Cardiff University; 8 Children and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust.

Lay Summary: Our previous research showed that most 4-8 year olds diagnosed with an Autism Spectrum Disorder (ASD) display concerning emotions and behaviours. These included hyperactivity and inattention, oppositional behaviour and fears and worries. Parents told us these difficulties were leading to further impairment and additional family stress, therefore effective intervention is needed. There is emerging evidence that parenting interventions could be effective in reducing concerning emotions and behaviours displayed by young children with ASD. The aim of the ASTAR study is to develop and evaluate two group-based parent-focused interventions. The two interventions aim to help parents of young children with ASD, but each has a different focus. We are trying to find out the effects of these interventions for children and parents and if one approach is more helpful than the other. The study consists of two phases; a feasibility study and a pilot randomised controlled trial (RCT). In 2017 we completed the feasibility study, where we tested the interventions and the research assessments and got feedback from families to help us improve how to run the next phase of the study. During the pilot RCT phase, we will directly compare the two interventions. Before and after the interventions we will measure child behavioural and emotional wellbeing, parentsâ&#x20AC;&#x2122; perceptions of family life and their wellbeing, and parent-child interactions. This will help us understand if one intervention is more helpful than the other. The cost-effectiveness of the interventions will also be examined. State of Progress: Ongoing Abstract: Background: Most young children diagnosed with Autism Spectrum Disorders (ASD) display concerning and potentially problematic behaviours and emotions (Salazar et al., 2015). Emerging evidence suggests that parent training interventions may reduce these difficulties in young children with ASD (Postorino et al., 2017). However, previous evaluations of such interventions have varied in their use of blinded outcome measures, the mode of implementation, and the degree to which the curriculum focuses on reducing disruptive behaviour, managing anxiety, and improving social communication abilities, thus limiting the conclusions that can be drawn about their effectiveness. There is a need to systematically develop and evaluate a parent-focused intervention for reducing concerning behaviours and emotions

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in young children with ASD that is cost-effective and could be delivered within the NHS and the private and voluntary sectors. The Autism Spectrum Treatment and Resilience (ASTAR) study aims to develop and evaluate a group-based intervention designed to help parents manage these problems among young children with ASD. Methods: The study consists of two phases; a feasibility study and a pilot randomised controlled trial (RCT). It will compare the group-based parent training intervention to a second group-based parent-focused intervention to test the specific effect on reducing concerning behaviours and emotions among families with 4-8-year olds with ASD. During the first phase, the study procedures and the interventions were tested to check the acceptability to families and professionals. Following this, a pilot RCT is being conducted to directly compare the effects of the two interventions. Measures of parent-child interactions, parent- and teacher-rated child emotions and behaviours, parental experiences and stress, and use of services and costs are obtained at baseline and immediately after the intervention. Results: In 2017, we completed the feasibility study. Twenty-two parents (91% mothers and 9% fathers) and their 4-8-year old child with ASD were recruited through local clinical services and SEN schools and participated in the study. All but one of the children were male. Ten were at a mainstream school and 12 were at a special school. Feedback from families who were involved was used to amend the interventions and research procedures prior to commencing the pilot RCT in late 2017. Generally, feedback on the two interventions was positive and the research assessments were acceptable to families. Conclusion: Further results from the pilot RCT are needed to establish whether the group-based parent training intervention appears to have promising findings for reducing concerning behaviours and emotions. If so, further funding will be sought to conduct a definitive randomised control trial. Updates will be posted on our website: http://iamhealthkcl.net/research-studies/treatment/. Funding: National Institute of Health Research (UK). Publications: Pending

Predictive parenting: Developing a new group parent intervention for behavioural and emotional problems in children with ASD

Investigators: Dr Victoria Hallett1, Dr Lauren Breese1, Dr Jo Mueller1, Dr Megan Hollett1, Prof Andrew Pickles2, Dr Vicky Slonims3, Prof Emily Simonoff4, Prof Stephen Scott1,4 & Prof Tony Charman5 1 South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Biostatistics and Health Informatics, IoPPN, KCL; 3 Evelina London Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust; 4 Department of Child and Adolescent Psychiatry, IoPPN, KCL; 5 Department of Psychology, IoPPN, KCL.

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Lay Summary: Children with autism spectrum disorder (ASD) are at risk of developing long lasting problems with behaviours and emotions, including “meltdowns”, self-injury and anxiety. Research has suggested that working with parents of children with ASD, in a group setting, can reduce the frequency and impact of these difficulties. We have developed a new 12-week parenting group for parents of young children with ASD. Importantly, it is the first group treatment to support parents to manage their child’s behavioural and emotional difficulties within the same programme. It is also the first to be developed specifically for children with ASD; with adaptions for children with both high and low levels of language. The “Predictive Parenting” group makes use of the important observation that children with autism have difficulties making predictions. This observation helps to explain why children with ASD struggle with unpredictable changes, sensations and social interactions. The group supports parents (1) to better predict their children’s behaviours and emotions; (2) to make their child’s life more predictable; and (3) to support their child to cope when things are unpredictable. It incorporates well-researched strategies, providing opportunities for practice both in the group and for homework. Within the ASTAR Study, we are testing whether Predictive Parenting helps to reduce children’s problematic behaviour and anxiety and to boost parenting confidence and ability. In the first stage of the trial, parents were very enthusiastic about the idea, content and structure of the group. We are now running a pilot trial, to explore whether it is more effective than another group treatment for ASD. State of Progress: Ongoing Abstract: Background: The majority of children with autism spectrum disorders (ASD) have been shown to experience impairing co-morbid difficulties with behaviours and emotions (Simonoff et al, 2008). These difficulties often persist into adolescence and adulthood, causing impairment and distress. Research has shown that parent-training (PT) interventions can help to reduce disruptive behaviours (Postorino et al, 2017) and anxiety (Ung et al, 2014) in children with ASD. However, to date, interventions have not been designed specifically for children with ASD and have not been suitable for the full range cognitive functioning and language ability in ASD. Programmes have also tended to target either behavioural or emotional difficulties. There is a pressing need for the development and evaluation of new interventions for both disruptive behaviour and anxiety that are suitable across a broad range of ASD functioning, cost-effective for use within NHS settings and systematically evaluated within large-scale trials. Methods: The current study explored the evidence-base for parenting interventions in children with ASD, including group and individual interventions for disruptive behaviour and anxiety. It extracted key strategies from previous programmes and explored why they are useful in an ASD population. In particular, the review considered how key PT approaches can be understood in terms of current ASD knowledge. A conceptual, hypothesis-driven framework is explored for a new group for parents of young children with ASD (both verbal and minimally verbal). Here, we outline the rationale and structure of the group, and discuss parent reactions from an initial feasibility trial. Results: Previous PT interventions have incorporated a range of strategies including: functional analysis; increasing structure and routine; visual approaches; positive and negative consequences; mindfulness approaches; social stories and CBT for anxiety. The current study discusses how each of these

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strategies can be understood in terms of the “Disorder of Prediction” (DoP) hypothesis of ASD. This theory suggests that core deficits in ASD can be understood in terms of a child’s difficulty making effective predictions. For example, DoP can help explain why unpredictable sensory inputs, social situations and schedules can trigger disruptive behaviour and anxiety. We used the DoP hypothesis to develop a novel intervention, incorporating previous evidence-based strategies. The Predictive Parenting group incorporates three themes (1) predicting behaviour more effectively; (2) making life more predictable where possible; (3) helping children cope with unpredictability. An initial feasibility study has shown that parents found the group to be accessible, engaging and clinically-relevant for their children’s needs. Conclusion: Predictive Parenting shows promise as a new, theory-driven parent intervention for disruptive behaviour and anxiety in children with ASD. Further work is underway to test its efficacy and costeffectiveness in a pilot randomised controlled trial, compared to an psycho-educational control group. Funding: National Institute of Health Research Programme Grant for Applied Research (UK). Publications: Pending

Managing anxiety in children and young people with autism spectrum disorder

Investigators: Prof Emily Simonoff1, Dr Ann Ozsivadjian2, Dr Rachel Kent1, Sophie Carruthers3 & Livvy Bridge3 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Evelina London Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust; 3 Department of Psychology, IoPPN, KCL.

Lay Summary: Between 70 and 90% of people with autism spectrum disorders (ASD) experience co-existing mental health disorders that cause them additional disorders and inhibit their participation in school, family life and other community activities. Anxiety disorders are amongst the most common, with 40% meeting diagnostic criteria for at least one disorder and more experiencing significant symptoms. While there is emerging evidence that cognitive behaviour therapy (CBT) can be effective, there is a gap in NHS provision, in relation to both identification of these conditions and the specialist adaptions required for people with autism. Furthermore, not all people with ASD and anxiety will require individual intervention and some may benefit self/parent/carer-administered psychoeducation and management strategies. No such programmes were available, however, and to address this gap, we developed and evaluated a set of manuals directed at adolescents and young adults with ASD and anxiety, as well as their parents/carers. In this feasibility study we randomised participants with a clinical diagnosis of ASD and high levels of anxiety to immediate versus delayed receipt of the toolkit. We evaluated their knowledge and confidence (primary outcome) as well as reduction in anxiety and improvement in quality of life. A total of 34 parent/patient dyads were randomised and 28 (14 in each group) completed the eight-week study. In terms of acceptability and usefulness, 96% (26/27) of parent/caregivers reporting that it was at least “somewhat likely” that they would recommend the guides to friend in need of similar help and 67% reporting that it was “very likely”. Effect size estimation for reduction in

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anxiety was promising. Further work is now focusing on developing an app-based platform to increase usability and flexibility of the toolkit. State of Progress: Toolkit development and evaluation are completed. App development and evaluation are ongoing. Abstract: Background: Between 70 and 90% of people with autism spectrum disorders (ASD) experience co-existing mental health disorders that cause them additional disorders and inhibit their participation in school, family life and other community activities. Anxiety disorders are amongst the most common, with 40% meeting diagnostic criteria for at least one disorder and more experiencing significant symptoms. A meta-analysis of randomised clinical trials (RCTs) of cognitive behaviour therapy (CBT) to reduce anxiety demonstrated significant effect sizes can be effective, although there were limitations to the trial designs (Sukhodolsky et al., 2013). The CBT interventions evaluated in this meta-analysis were all modified to take account of differences in cognitive and emotional style of people with autism and require specialist knowledge of autism to administer. There is a gap in NHS provision, with too few services having the specialist skills to identify and treat mental health problems such as anxiety in people with ASD (National Autistic Society, 2010). To help fill this gap, we developed and evaluated the acceptability and usability of a toolkit aimed at parents/carers and older children/adolescent/adults with ASD and anxiety. The toolkit builds on the evidence that psychoeducation is an important first step for psychological interventions and that, for milder conditions, self-help interventions may be as effective as interventions delivered by mental health professionals. The aim was to provide materials that could be universally and easily accessible as the first element of a stepped care approach. Methods: The aim of the psychoeducation toolkit is to provide generic information about how to recognise anxiety in young people with ASD and present some strategies that have previously been suggested to help manage and reduce anxiety symptoms. The content is based on research on existing self-help books for anxiety not specific to ASD and cognitive behavioural exercises used in clinical practice with individuals ASD. Participants identified from local mental health services. Eligibility criteria were: young people aged 8-25 years old with a clinical diagnosis of ASD and high levels of anxiety (exceeding the clinical cut-offs on the parent-reported Screen for Child Anxiety and Related Disorders. We required a mental age of ≥8 years in participants and parents/carers and participants needed to have a confident use of English. Participants were randomised (1:1) to immediate or delayed (4 weeks later) receipt of the toolkit. Its contents were explained to them and weekly phone calls checked their use and addressed any questions or concerns. Evaluations were undertaken at 4 and 8 weeks following randomisation. The primary outcome measure was participant/parent/carer knowledge and confidence but we also obtained measures or anxiety symptoms and quality of life to calculate pilot effect sizes. Results: We randomised 34 participants; 28 fully completed the trial. In terms of acceptability and usefulness, 96% (26/27) of parent/caregivers reporting that it was at least “somewhat likely” that they would recommend the guides to friend in need of similar help and 67% reporting that it was “very likely”. Pilot effect sizes are promising for reduction in anxiety, but smaller for improvement in quality of life. Qualitative interviews with participants and parent/carers suggested that the medium (paper and pencil manual) was cumbersome, not portable, and somewhat inflexible. Many asked for more time than the 4 weeks to complete all the elements of the toolkit. In some cases, opportunities to try out some of the suggestions had not occurred or been taken up. Younger participants needed considerable scaffolding from parents/carers to use the toolkit. 152

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Conclusion: The toolkit is a promising new intervention to include in a stepped care approach to the management of anxiety in ASD, with the potential to be universally accessible at an early stage in the development of symptoms. In order to meet some of the comments from users, an app format has the potential to be less cumbersome and more flexible, as well as to provide ready ways of capturing dynamic information about symptoms and their response to interventions. A hackathon hosted by Deutsch Bank outlined app prototypes which are being used to develop an app, with people with ASD, that we will then evaluate. Funding: Autistica, hackathon organised by Deutsche Bank, additional funding to evaluate the app from the Maudsley Charity. Publications: In preparation.

Early caregiving predicts attachment representations in adolescence: Findings from two longitudinal studies

Investigators: Prof Stephen Scott1 & Prof Thomas Oâ&#x20AC;&#x2122;Connor2 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Department of Psychiatry, University of Rochester Medical Center, NewYork, USA.

Lay Summary: Being able to trust that your parents are there for you when you are in danger, frightened, upset or worried is an important characteristic, not only for infants, but also in middle childhood. We are interested in seeing what might determine this in teenagers, whether early experience still matters, or whether actually all the other things that come along like peer pressure and school etc. make what happened in the early years no longer important. State of Progress: Completed January 2080 Abstract: Background: A growing research base demonstrates that adolescentsâ&#x20AC;&#x2122; construction of secure attachment relationships may underlie successful social and personal relationships and healthy behavioural adjustment. Little is known about the early caregiving origins of adolescent attachment security; this study provides some of the first data on this topic. Methods: The relative contribution of early and current caregiving quality to attachment security in adolescence was assessed in two longitudinal follow-up studies of a clinic and community sample using identical measures (n=209). Quality of early parent-child relationships at age 4-7 years of age and parentadolescent relationship quality at approximately 12 years were assessed using observational methods; psychosocial risk was derived from extensive interview and questionnaire assessments; adolescent attachment quality was assessed using a standard attachment interview.

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Results: Analyses indicated moderate stability in observed parent-child interaction quality from early childhood to adolescence. Observational ratings of both early childhood and current caregiving quality were significantly associated with adolescent attachment security, but early caregiver sensitivity was more strongly associated with adolescent attachment security and predicted later attachment security independently from current caregiving quality. Follow-up analyses indicated that this longitudinal prediction was significantly weaker in the clinic than community sample. Conclusion: Parental sensitive responding in childhood has enduring effects on attachment representation in adolescence, independent of current parenting relationship quality. These findings provide important new evidence supporting early parenting interventions for promoting youth well-being and adjustment. Funding: Department for education to national Academy for parenting research Publication:

Early caregiving predicts attachment representations in adolescence: Findings from two longitudinal studies. Under review, Journal of Child Psychology and Psychiatry

Personalised assessment and intervention packages for children with conduct problems

Investigators: Prof Stephen Scott1 & Dr Rob Senior2 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 2 Tavistock and Portman NHS Foundation Trust

Lay Summary: Fully 5% of children are persistently rude, aggressive, disobedient, angry and break the rules. Unfortunately, as well as being difficult to manage at home and at school in childhood, at least half go on to poor outcomes as adults, including crime, domestic violence, drug misuse, leaving school with no qualifications, becoming unemployed and depending on state benefits. The standard treatment, recommended by NICE, is group parent training, which is effective for about two thirds of cases. However, for the remaining one third, the problem still persists, either because the parents were unable to use the techniques taught, or because there are particular characteristics about the child, making them and responsive. In this programme we are working with parents to develop a way of giving them new skills that are tailored to their needs (personalised), and find out whether this works better than current parent training. We have just finished profiling 150 parents (e.g. whether they suffer from depression, are they in an unsupportive or abusive relationship) and children (e.g. are they autistic, do they have severe ADHD), and we have followed through standard group parent training using a high quality programme, the Incredible Years. We have carried out in depth interviews with parents who successfully completed the training and those who did not. These are giving is valuable insights about parents views about what works and what does not.

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We are now developing a new manual based on these findings to give completely individual treatment, often in the parents home where they cannot get to clinic appointments. This will be tested in a randomised controlled trial to check its superiority against and parent training. State of Progress: Ongoing Abstract: Aim: The overarching aim of the work is to develop an improved treatment for conduct problems that can be readily implemented in the NHS. Objectives

(1) Identify groups with good and poor outcomes from standard parent training for qualitative study, and identify quantitative predictors of outcome to identify factors that should be incorporated in the new intervention (2) Work with parents to develop a new personalised treatment approach for conduct problems. (3) Conduct an RCT to compare the personalised approach with standard parent training. Work plan Work stream 1: systematic review of personalised treatment for mental health problems in children and

adults. Work stream 2: prospective study of parent training for the parents of 160 children referred with conduct

problems followed up at 3 and 6 months. This will establish 3 groups for qualitative study, (1) 25 parents of children with a good outcome (2) 25 parents who either did not attend any training sessions or who dropped out and (3) 25 parents who attended but whose children did not improve. Economic hardship, parental depression, high callous unemotional traits, marital discord or single parent status, and parental hostility will be examined in logistic regression as predictors of outcome as a basis for creating a screening tool for the RCT. Work stream 3: qualitative study with parents in the 3 groups identified in WS2. Interviews will invite

parentsâ&#x20AC;&#x2122; accounts of their experience of parent training and explore the reasons for the various outcomes and parentsâ&#x20AC;&#x2122; perception of the possible role of factors identified quantitatively in WS2. Work stream 4: work with parents identified from WS2 and WS3, to develop a personalised approach

to treatment. The outcome will be a treatment manual for the personalised approach, a training programme, and a set of criteria for judging fidelity. Work stream 5: feasibility study of the personalised approach with nine CYP-IAPT staff each working

with 5 children. Work streams 6 and 7 (WS6, WS7): internal pilot and, if successful, full scale RCT to compare the

personalised approach with standard parent training. From an initial sample of the parents of 150 children the screening procedure devised in WS2 will be used to generate a sample of 90 for randomisation and follow up at 3, 6, and 9 months using the same baseline predictors and follow up measures as in WS2. If the pilot supports the feasibility we will proceed to the full scale RCT to generate a total sample of 450 yielding, after screening, 270 for randomisation. The primary outcome measure will be the conduct problems score of the PACS. The screen increases the statistical power of the sample by omitting parents of children likely to do well with standard treatment, and we predict the sample will provide 80% power to detect an effect size of 0.35, at p = .05. Economic evaluation: the costs of the two treatments will be compared using a standard net benefit

approach. Projected outputs and dissemination: Publication in high quality peer reviewed journals will be the priority to ensure rigorous scrutiny of the 155

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findings. If the personalised approach is superior we will seek to make it widely available in the NHS through CYP-IAPT, and will present findings to a wide range of health professionals. Benefits to patients and the NHS: The long-term outlook for children with conduct problems will be improved, with less suffering, better functioning, and greater mental health. The personalised approach will greatly increase the ability of the NHS to reach children not helped by current approaches, with the potential that this will be at no added cost leading to substantial economic gains. Funding: NIHR £2.4m.

Harnessing the power of individual participant data in a meta-analysis of the benefits and harms of the incredible years parenting program

Investigators: Prof Stephen Scott1 & Prof Frances Gardner2 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Social Policy and Intervention, University of Oxford.

Lay Summary: Conduct problems are a major child mental health problem. Whilst parent training is an established effective treatment to improve them, it is uncertain how much they improve family functioning more generally, or whether they improve emotional symptoms and symptoms of ADHD. Most analyses just compare different studies as a whole, whereas here we merged all the individual level data to make direct evaluation of effectiveness on 1800 children. State of Progress: Completed March 2018 Abstract: Background: Parenting programs aim to reduce children’s conduct problems through improvement of family dynamics. To date, research on the precise benefits and possible harms of parenting programs on family well-being has been unsystematic and likely to be subject to selective outcome reporting and publication bias. Better understanding of program benefits and harms requires full disclosure by researchers of all included measures, and large enough numbers of participants to be able to detect small effects and estimate them precisely. Methods: Accordingly, we obtained individual participant data for 14 out of 15 randomised controlled trials on the Incredible Years parenting program in Europe (total N = 1799). We used multilevel modeling to estimate program effects on thirteen parent-reported outcomes, including parenting practices, children’s mental health, and parental mental health. Results: Parental use of praise, corporal punishment, threats and shouting improved, whilst parental use of

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tangible rewards, monitoring, or laxness did not. Children’s conduct problems and ADHD symptoms improved, whilst emotional problems did not. Parental mental health (depressive symptoms, selfefficacy, stress) did not improve. There was no evidence of harmful effects. Conclusions: The Incredible Years parenting program improves the aspects of family well-being that it is primarily designed to improve: parenting and children’s conduct problems. It also improves parent-reported ADHD symptoms in children. Wider benefits are limited: the program does not improve children’s emotional problems or parental mental health. There are no signs of harm on any of the target outcomes. Funding: NIHR Publications: 1.

Leijten P, Gardner F, Landau S, Harris V, Mann J, Hutchings J, Beecham J Bonin E-M & Scott S. (2018). Harnessing the power of individual participant data in a meta-analysis of the benefits and harms of the incredible years parenting program. Journal of Child Psychology and Psychiatry, 59: 99-109. Gardner F, Leijten P, Melendez-Torres G, Landau S, Harris V, Mann J, Beecham J, Hutchings J & Scott S. (2018). The earlier the better? Individual participant data and traditional meta-analysis of age effects of parenting interventions for pre-adolescent children. Child Development in press.

Multi-systemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): A randomised controlled trial

Investigators: Prof Stephen Scott1, Prof Peter Fonagy2 & Prof Ian Goodyer3 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Clinical, Educational and Health Psychology, University College London; 3 Section of Developmental Psychopathology, Department of Psychiatry, University of Cambridge.

Lay Summary: Adolescent delinquents and criminal behaviour is a major social problem. While some interventions appear to work in the USA, they have not been tested in the UK, where management as usual, may be better, so he may not be worth investing in them. State of Progress: Completed February 2018 Abstract: Background: Adolescent antisocial behaviour is a major mental and physical health and social problem. Multisystemic Therapy (MST), a National Institute for Health and Care Excellence-recommended structured intensive intervention addressing multiple risk factors associated with adolescent antisocial behaviour, has been shown in US trials to reduce symptoms and offending rate, but non-US findings are equivocal. 157

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Methods: We report an 18-month pragmatic, individually randomised, single-blind, controlled superiority trial conducted in nine community-based MST services in England. Adolescents (aged 11–17 years) with moderate to severe antisocial behaviour received either management as usual (MAU; n=342) from statutory and voluntary services or standard MST lasting 3–5 months followed by MAU (n=342). Primary outcome was proportion of out-of-home placements. Secondary outcomes included time to first offence, number of offences registered on the Police National Database reconviction rates, total service and criminal justice sector costs, participant wellbeing, and substance misuse, measured at baseline and 6, 12 and 18 months (primary endpoint). We used logistic regression for the primary outcome and suitable mixed-effects regression models for secondary outcomes depending on the outcome type. Outcomes: At 18 months the treatment effect for out-of-home placement was not significant (OR 1·25, 95% CI 0·77–2·05; p=0·37). Time to first offence was also comparable (HR 1·06, 95% CI 0·84 to 1·33; p=0·64) but the number of offences was higher for the MST group at 18 months (0·65, 95% CI 0·28–1·02; p=0·00067). In longitudinal models there were consistent short-term symptom reductions from MST in some secondary outcomes (self-reports of depression and parental reports of delinquency), but no evidence of sustained superiority on most secondary outcome measures with the exception of parental wellbeing and self-reported callous and unemotional behaviour. Improvements were notable in both arms of the trial, with >40% reduction in conduct disorder diagnoses. Mean total service costs were not significantly different (MST: £28,687 vs MAU: £30,928; adjusted difference –£1623, 95% CI –£7684 to £4438; p=0·60). Interpretation: We found no evidence that MST followed by MAU contributed to behavioural or cost outcomes by 18 months for adolescents with moderate to severe antisocial behaviour problems. MST achieves some early symptomatic gains on parent-rated outcomes, but not those based on independent records, which after 12 months favour MAU. The findings do not support MST over MAU as the intervention of choice for children and adolescents with moderate to severe antisocial behaviour. Funding: £2.1m (Department for Children, Schools and Families in conjunction with the Department of Health). Publication:

Fonagy P, Butler S, Cottrell D, Scott S, Pilling S, Eisler I, Fuggle P, Kraam A, Byford S, Wason J, Ellison R, Simes E, Ganguli P, Allison E & Goodyer I. (2018). Multisystemic Therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): A randomised controlled trial. Lancet Psychiatry, 5: 119-133.

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Randomised controlled trial of functional family therapy (FFT) for offending and antisocial behaviour in UK

Investigators: Prof Stephen Scott & Dr Sajid Humayun Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL).

Lay Summary: For younger teenage antisocial youth, regular contact with agencies may not be effective as they tend to use just an individual model. We therefore need to know whether a more intensive home visiting programme that aims to change family dynamics may be effective. State of Progress: Completed 2017 Abstract: Background: Youth offending and antisocial behaviour (ASB) are associated with low quality mental health and relationships and usually lead to poor adult functioning; they are very costly for society. Family interventions are effective in children but there are few reliably effective and inexpensive interventions for adolescents. Functional Family Therapy (FFT) is an evidence-based intervention but seldom tested outside the United States. Methods: One hundred and eleven adolescents (10–17 years of age, M = 15.0, SD = 1.63) and their families were randomised to FFT + Management As Usual (MAU) (n = 65) or to MAU (n = 46). Assessments were made at baseline 6, and 18 months after randomisation and included interviews and questionnaires of parenting behaviours, conduct disorders (CDs) and offending. Parent–child interaction was directly observed and police records obtained. Trial registration: ISRCTN27650478. Results: Eighty-nine (80%) were followed-up. In both groups, there were large reductions over time in all measures of offending and antisocial behaviour (e.g. primary outcome p < 0.001), but no significant changes over time in parenting behaviour or the parent–child relationship. However, there were no differences between intervention and control groups at 6 or 18 months on self-reported delinquency, police records of offending, symptoms or diagnoses of CDs, parental monitoring or supervision, directly observed child negative behaviour, or parental positive or negative behaviour. Against predictions, the intervention group showed lower levels of directly observed child positive behaviour at 18 months compared to controls. Conclusions: In contrast to most previous trials of FFT, FFT+MAU did not lead to greater reductions in youth ASB and offending compared to MAU alone, and did not lead to improvements in parenting or the parent–child relationship. This may be because the trial was more rigorously conducted than prior studies; equally, the possibility that MAU was effective requires further research. Funding: Department for Education to National Academy for Parenting Research Publication:

Humayun S, Herlitz L, Chesnokov M, Doolan M, Landau S & Scott S. (2017). Randomized controlled trial of functional family therapy for offending and antisocial behaviour in UK youth. Journal of Child Psychology and Psychiatry, 58: 1023-1032. 159

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Figure 12. Directly observed parental positivity and self-reported delinquency and by treatment group and time (months)

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Helping families programme: An innovative parenting intervention for families with complex and multiple morbidities

Investigators: Dr Crispin Day1, Dr Lucy Harris1, Dr Joshua Harwood1 & Jackie Briskman2 1 Centre for Parent and Child Support, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: Children in families affected by multiple, coexisting psychosocial problems, such as parental mental health difficulties, family conflict and social adversity, are at much greater risk of developing mental health problems, educational and social difficulties. There is a significant gap in effective, evidencebased parenting interventions for this population. The Helping Families Programme has been developed to address this gap. Our research and dissemination programme demonstrates that the Helping Families Programme is a promising and effective intervention in trial and real-world settings. State of Progress: Ongoing Abstract: Background: Children from families that experience complex and multiple morbidities, such as parental mental health problems, child neglect, family conflict and social adversity, are at much greater risk of poorer immediate and long-term developmental outcomes. These adverse outcomes include mental and physical health difficulties, lower educational attainment, substance misuse and criminality. These negative individual and family impacts together with associated social and economic burden maintain the intergenerational transmission of adversity. Because of the complex nature of their difficulties, families often struggle to receive effective intervention. The Helping Families Programme (HFP) has been developed to provide effective parenting intervention for families with complex and multiple morbidities. HFP is a manualised, one-to-one intervention that enables parents to develop the emotional regulation, interpersonal and parenting skills to nurture and care for their children safely. Methods: HFP has been evaluated in a series of mixed methods pilot and feasibility studies to examine its clinical and economic impact (Day et al., 2012, Stephens et al., 2014). We are currently completing a pilot randomised control trial with the intention of conducting a full-scale pragmatic RCT. Results: Our pilot studies conducted in childrenâ&#x20AC;&#x2122;s social care services show reductions in child metal health, safeguarding and school difficulties (Day et al., 2011, Stephens et al., 2014). Evidence from our qualitative studies highlight the significant parenting difficulties experienced by families with complex and multiple morbidities as well as their frequent negative experiences with mental health and social care services (Wilson et al.). Our most recent feasibility, pilot RCT for parents with significant interpersonal and personality difficulties is in the final stage of data analysis. Qualitative findings from the trial suggest that HFP has effective methods for engaging parents in an effective parenting intervention. Trial feasibility findings will be published in autumn 2018. Our research programme is supported by dissemination and implementation in routine mental health and childrenâ&#x20AC;&#x2122;s social care services. 161

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Conclusion: Our Helping Families Programme research highlights the significant gap in effective, evidence-based intervention for children and families affected by complex and multiple morbidities. This under-served group are at high risk of poor developmental outcomes and intergenerational adversity. Our findings suggest that the Helping Families Programme is a promising evidence-based intervention that is feasible to deliver in routine service settings and research trials. Funding: National Institute for Health Research, Department for Education Publications: 1.

Day C, Briskman J, Crawford M, et al. (2017). Feasibility trial of a psychoeducational intervention for parents with personality difficulties: The Helping Families Programme. Contemporary Clinical Trials Communications, 1-8. 2. Wilson R, Michelson D, Weaver T & Day C. Experiences of parenting an clinical intervention for mothers affected by personality disorder: A pilot qualitative study combining parent and clinician perspectives. BMC Psychiatry (Accepted for publication) 3. Stevens M, Harris L, Ellis M, Day C & Beecham J. (2014). Investigating changes in use of services by high-need families following the Helping Families Programme, an innovative parenting intervention for children with severe and persistent conduct problems. Child and Adolescent Mental Health, 19(3):185-193. doi: 10.1111/camh.12035 4. Day C, Ellis M & Harris L. (2012) Helping Families Programme Manual. South London & Maudsley NHS Foundation Trust/Kingâ&#x20AC;&#x2122;s College, London. 5. Day C, Kowalenko S, Ellis M, et al. (2011). The Helping Families Programme: A new parenting intervention for children with severe and persistent conduct problems. Child and Adolescent Mental Health. 16 (3):167-1721. doi: 10.1111/j.1475-3588.2010.00588.x

Empowering parents, empowering communities (EPEC): A popular, cost effective parenting programme for socially disadvantaged and excluded families

Investigators: Dr Crispin Day, Dr Joshua Harwood, Nadine Kendall & Jo Nicoll Centre for Parent and Child Support, South London and Maudsley NHS Foundation Trust.

Lay Summary: Empowering Parents, Empowering Communities (EPEC) is an innovative popular, cost effective parenting programmes for socially disadvantage and excluded families. It has been successfully tested in an ongoing research programme using a range of randomised, quasi-experimental and qualitative methods. One of the UKâ&#x20AC;&#x2122;s best evidenced parenting programmes, EPEC is a core part of early intervention and community parenting services across London. The EPEC Scaling Programme is currently setting up 16 new sites in England and Australia. Abstract: Background: Parenting interventions, particularly those delivered in a group format, are an effective approach for many childhood social, emotional and behavioural difficulties. However, families experiencing social disadvantage, exclusion and higher levels of need are less likely to use and benefit from these approaches. The scale of need in socially disadvantaged areas far outweighs the service capacity available, and profession-led parenting services can be complex to access and stigmatising for families to use. 162

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EPEC combines parent-led parenting groups with training, organisational support and supervision provided by specialists in child mental health and parenting. There are three core parenting programmes: (1) My Baby and Us for parents of babies aged up to one year, (2) Being A Parent for parents with children, aged 2-11, and (3) Living with Teenagers for parents of children aged 11-16 years. Methods: EPEC has an active research and development programme using randomised and quasi-experimental trials as well as qualitative methods to demonstrate its impact on parenting behaviour and reflective function, child behaviour, parents’ wellbeing, family functioning, and social and community connectedness Results: Our randomised control trial (Day et al., 2012) demonstrated significant improvements in child behaviour, parenting behaviour and parent goal attainment, ranging from medium to large effect sizes. Subsequent research has demonstrated the effectiveness of EPEC for parents living in homeless accommodation. Recent research studies have demonstrated the impact of EPEC on parental reflective function, mother-infant interaction, parental knowledge and confidence (Harwood, 2017, Fenandez, 2018). Qualitative and quantitative studies have explored the unique role of EPEC’s peer-led approach (Day, Kearney & Squires, 2017; Thomson, Michelson & Day, 2014) Conclusion: EPEC is one of the best evidenced and innovative parenting programmes developed in the UK. It’s unique approach is popular in reaching excluded and socially disadvantaged families and effective in transforming outcomes. It is widely available through routine services across London. A funded scaling programme is supporting 16 new EPEC sites across England. EPEC is also established in Australia. EPEC has been translated into Spanish, Japanese, Hindi, Burmese, Vietnamese and Arabic. Funding: Guy’s and St Thomas’ Charitable Foundation, South London & Maudsley NHS Foundation Trust, NESTA/Dept of Digital, Culture, Media & Sport State of Progress: Ongoing Publications: 1.

Day C, Michelson D, Thomson S, Penney C & Draper L. (2012). An 8-week peerled parenting intervention reduces parent-reported behavioural problems in socially disadvantaged children. Evidence-Based Mental Health. doi:10.1136/ebmental-2012-100737 2. Day C, Michelson M, Thomson S, Penney C & Draper L. (2012) Evaluation of a peerled parenting intervention for child behaviour problems: A community-based randomised controlled trial. British Medical Journal, 344:e1107 doi:10.1136/bmj.e1107 3. Day C, Michelson D, Thomson S, Penney C & Draper L. (2012). The Empowering Parents, Empowering Communities: A peer-led parenting programme. Child and Adolescent Mental Health. 17(1):52–57. doi:10.1111/j.1475-3588.2011.00619.x 4. Winter R. (2013). Empowering Parents Empowering Communities. Melbourne: Murdoch Children’s Research Institute/Tasmanian Early Years Foundation. 5. Charalambides M. (2013). An evaluation of peer-led parenting groups in routine practice. MSc Thesis. King’s College, London. 6. Michelson D, Ben-Zion I, James A, Draper L, Penney C & Day C. (2014). “Living with teenagers”: Evaluation of a peer-led parenting intervention for socially disadvantaged families with adolescent children. Archives of Disease in Childhood. 99:731–737. doi:10.1136/ archdischild-2013-304936.

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Thomson S, Michelson D & Day C. (2014). From parent to “peer facilitator”: A qualitative study of a peer-led parenting programme. Child: Care, Health & Development, 41(1): 76-83. doi:10.1111/cch.12132. 8. Bradley C. (2016) Empowering Parents, Empowering Communities: Temporary Accommodation: A feasibility study of a peer-led parenting intervention for parents living in temporary accommodation. Clinical Psychology Doctoral Thesis, Canterbury Christ Church University. 9. Day C, Kearney C & Squires F. (2017). Art, science and experience of peer support: Learning from the Empowering Parents, Empowering Communities Programme. International Journal of Birth and Parent Education, 4(2). 10. Harwood J. (2017). The impact of a behavioural parenting intervention on parental reflective function. Clinical Psychology Doctoral Thesis, Royal Holloway, University of London. 11. Fernandez L. (2017). Baby and Us: Assessing the effectiveness of a psychosocial intervention for new parents and their babies. MSc Thesis. King’s College, London.

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Paediatric autism communication trial-generalised (PACT-G)

Investigators: Prof Tony Charman1, Prof Andrew Pickles2, Prof Patricia Howlin3, Prof Richard Emsley2 & the PACT-G Consortium. 1 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Department of Biostatistics and Health Informatics, IoPPN, KCL; 3 Department of Child & Adolescent Psychiatry, IoPPN, KCL. This study is a collaboration between Central Manchester University NHS Trust, University of Manchester, Newcastle University, King’s College London, Guy’s and St. Thomas NHS Foundation Trust, Evelina Children’s Hospital, led by Prof. Jonathan Green (University of Manchester).

Lay Summary: Previous research found that a therapy to enhance parent-child communication in children with autism can help to improve their social communication. However, the children’s gains did not spread more widely to the school environment. The ‘Paediatric Autism Communication Trial-Generalised’ (PACT-G) study will test whether working with parents and education staff, across home and school settings, will help children with autism transfer their improving communication skills into new settings. The study includes children with autism aged between 2 and 11 years, half of whom receive PACT-G therapy in addition to usual clinical services, and half of whom continue to receive the usual services only. At the end of the study, we will compare the two groups of children on a range of assessments to see whether the children who received PACT-G therapy showed improved skills and if they are able to transfer their new communication skills across settings. The results of the study will help us to understand whether PACT-G therapy benefits children with autism. More generally, the findings should help in the development of therapy and education for children with autism throughout the UK. State of Progress: Ongoing Abstract: Background: The evidence base for early intervention in autism shows that behaviours proximal to the intervention delivered (e.g. dyadic interaction measures) are amenable to change. However, it has been difficult to generalise treatment gains successfully acquired from one context into another, and no studies to date have demonstrated improvement in general autism symptom severity. In this study, the Paediatric Autism Communication Trial-Generalised (PACT-G), we want to extend the parent-child therapy model to see if we can help children to transfer newly acquired social communication skills from home to school. We hope to achieve this by delivering the therapy to (1) a parent, who can work with the child at home, and (2) a key support person, such as a learning support assistant, who can work with the child at school. We hope to generate similar changes in these two contexts by working with school staff using the same techniques as we do with parents. Methods: PACT-G is a multisite randomised controlled trial of the PACT-G therapy plus treatment as usual (TAU) compared to TAU alone. Children are included in the study if (1) they meet criteria for ‘core’ autism on the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2); (2) they have a nonverbal ability age equivalent of more than 12 months; and (3) the school or education setting agrees to take part in the study. Assessments of the children’s language, social communication and interaction skills are administered at baseline (prior to treatment allocation), and at 7- (midpoint) and 12-month (endpoint) intervals, so that we can assess the impact of the PACT-G intervention across preschool and middle childhood. 166

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Results: The primary trial outcome is the change in autism symptoms at endpoint, measured using the ADOS2. Further analysis will also help us to understand the mechanism behind the generalisation of skills across settings. Conclusion: This trial provides a unique opportunity for us to investigate how children with autism generalise skills across settings – an important question in the developmental science of autism. We also hope that delivering the intervention across two contexts will have a greater impact on the child’s development. If this kind of integrated approach has benefits for the child and the family, this will have important implications for future service delivery models. Funding: National Institute of Health Research and the Medical Research Council (Efficacy and Mechanism Evaluation Programme) Publications: 1.

Green J, Charman T, McConachie H, Aldred C, Slonims V, Howlin P, ... & The PACT Consortium. (2010). Parent-mediated communication-focused treatment in children with autism (PACT): A randomised controlled trial. The Lancet, 375(9732):2152-160. doi: 10.1016/S0140-6736(10)60587-9 2. Pickles A, Harris V, Green J, Aldred C, McConachie H, Slonims V, ... Charman T. (2014). Treatment mechanism in the MRC preschool autism communication trial: implications for study design and parent-focussed therapy for children. Journal of Child Psychology and Psychiatry, 56(2):162-170. doi: 10.1111/jcpp.12291 3. Byford S, Cary M, Barrett B, Aldred CR, Charman T, Howlin P, … & The PACT Consortium. (2015). Cost-effectiveness analysis of a communication-focused therapy for pre-school children with autism: results from a randomized controlled trial. BMC Psychiatry, 15(316). doi: 10.1186/s12888-015-0700-x 4. Pickles A, Le Couteur A, Leadbitter K, Salomone E, Cole-Fletcher R, Tobin, H, ... & Aldred C. (2016). Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. The Lancet, 388(10059): 2501-2509. doi: 10.1016/S0140-6736(16)31229-6

Social contagion?: Using administrative data to examine risk factors in schools for indicators of adolescent adversity and distress

Investigators: Dr Ruth Blackburn1, Prof Ruth Gilbert1, Prof Chris Bonell2, Dr Johnny Downs3, Prof Simon Gilbody4, Prof Anders Hjern5 , Prof Alastair Leyland6 & Dr Alexandra Pitman7 1 Department of Paediatric Clinical Epidemiology, University College London; 2 Department of Public Health Sociology, London School of Hygiene and Tropical Medicine; 3 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 4 Department of Health Services Research, University of York; 5 Department of Paediatric Epidemiology, Karolinska Institute; 6 Department of Applied Statistics, University of Glasgow; 7 Department of Psychiatry, University College London.

Lay Summary: It has been difficult for researchers to understand why young people self-harm. Research has provided answers to some questions to understand which young people may be more vulnerable to self-harm, 167

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but we do not have good levels of evidence that reveal what the specific triggers are or causes selfharm. This has made it difficult to draw up plans on how best to prevent it. One area that seems to be important is school life and class friendships. Some studies show that if young people have a friend or classmate who has started self-harming, then that will increase the chance of them self-harming; a term used by self-harm researchers for this is “social contagion”. At the moment we do not have a clear sense of how much social contagion contributes to the amount of self-harm that we see in young people. Dr Blackburn and colleagues will soon start a 3-year study, which aims to investigate this by using very large databases of routinely collected information from Child and Adolescent Mental Health Services (CAMHS), General Practitioners and Schools. This study will support decision makers to understand how best to tackle social-contagion and reduce self-harm within schools. State of Progress: Future Abstract: Background The causes of self-injury in young people are varied and highly complex, reflecting biological, social and personality factors in tandem with environmental triggers, which could be appropriate targets for intervention (e.g. exposure to others’ self-injurious behaviour). We currently lack objective measures of the scale and clustering of self-harm behaviours in schools, because studies in this field have often used cross-sectional or panel (repeated survey) designs that do not capture the precise timing of events or are not mapped to schools. Linkage of administrative data on schools to EHR offers a powerful opportunity to describe the spread of health behaviours through peer groups as a time-stamped chain of events. Profiling features of the exposome that predict self-harm is of practical value for public health planning (e.g. predicting future burden) and for trials (e.g. guiding identification and selective recruitment of higher risk schools or hospitals into trials of interventions, and extrapolating the findings beyond the trial population). Objective 1.

Phenotyping the clinical iceberg of adolescent self-harm: (1) decipher the complexity of EHR for a spectrum of care settings (primary care, Child and Adolescent Mental Health Services, A&E, inpatient admissions) by applying NLP and machine learning approaches to refine existing clinical phenotypes for self-harm with existing HDR-London data and linkages (2) implement the refined clinical phenotypes in three national cohorts of school leavers created by secondary care and education data linkage for England (n≈550,000 – anticipated mid 2018), Scotland (n=284,629) and Sweden (n=871,402) Objective 2.

Profiling social contagion of self-harm in schools Develop algorithms for identifying clinically important presentations of social contagion of self-harm in schools, combining findings from studies to: (1) analyse the timing and sequence of self-harm cases in schools (e.g. unsupervised clustering, self-controlled case series) to classify clusters of self-harm that are indicative of social contagion; (2) identify individual and exposome characteristics that are associated with social contagion of self-harm by comparing clustered versus isolated self-harm cases, and pupils without self-harm (multinomial modelling); and (3) evaluate social contagion as a risk factor for clinically important long-term outcomes (e.g. premature mortality, pregnancy in adolescence) by comparing isolated and clustered self-harm cases (survival analysis)

Funding: Ruth Rutherford Fellowship, Health Data Research UK (R.B), Psychiatry Research Trust Peggy Pollak Fellowship (J.D); MQ Data Science award (J.D) the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. 168

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Linking education, social care and electronic health records for children attending mental health services

Investigators: Dr Johnny M. Downs1,2, Prof Tamsin Ford3, Prof Robert Stewart1,2, Hitesh Shetty2, Ryan Little3, Amelia Jewell2, Matthew Broadbent2, Dr Jessica Deighton4, Dr Tarek Mostafa5, Prof Ruth Gilbert6, Prof Matthew Hotopf2,7 & Prof Richard Hayes1,2 1 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 NIHR South London and Maudsley NHS Foundation Trust Biomedical Research Centre; 3 University of Exeter Medical School, UK; 4 Evidence Based Practice Unit, University College London and Anna Freud Centre, London; 5 UCL Institute of Education, University College London; 6 Administrative Data Research Centre for England, UCL Great Ormond Street Institute of Child Health, UK; 7 Department of Psychological Medicine, IoPPN, KCL.

Lay Summary: One of the most important outcomes for clinicians, parents and children in CAMHS is making sure their mental illness does not irreversibly impact on their life chances, especially by making sure they achieve the best they can in education. At present CAMHS services are unable to see what impact they make in medium to long-term on a young person’s school career. This is largely due to the way NHS health data is held separately from educational data in government systems. Up until now, there had been no successful link made between these systems – the technical, legal and data governance challenges had made it difficult to achieve. In 2015, researchers at the Child and Adolescent Department and NIHR Biomedical Research Centre achieved this, and were able to link over 270,000 children from South London to their CAMHS records. They have begun a number of studies to look how certain educational problems may lead to mental health problems, and also how CAMHS treatment may reduce the impact of mental health problems on school and educational achievement. This study explains the overall purpose of the linkages and the legal, governance and technical processes used to get this unique linkage to happen. It gives examples of how it is being used to improve public services for children, and discuss what is needed to implement this approach more widely across the UK State of Progress: Ongoing Abstract: Background: There are strong interconnections between public services which deliver health, education and social care for children. Improvement or withdrawal of any one of these services can help or harm delivery of the others. Because of their complementary nature, policy makers and service providers advocate that evaluations should involve linked routinely collected health and education data. Research using linked health, social and education data have been in place in Scotland and Wales for several years, but as of yet, no comparable linkage has been achieved in England. This work presents the governance, legal and technical challenges encountered in achieving this link for four local authorities in South London, and reviews implications for future analyses by researchers and policy makers. Methods: Approvals were sought from multiple government and ethical committees to link SLAM child and adolescent mental health service data to Department for Education (DfE) educational data held within the National Pupil Database. Under robust governance protocols delivered by the Maudsley BRC Clinical Records Interactive Search, and via an NHS trusted third party, I extracted the personal identifiers from the electronic health records of young people of a clinical cohort of all individuals

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aged between 4 and 18 years referred to NHS mental health care in England between 1st September 2007 and 31st August 2013. The DfE used combined fuzzy and deterministic approaches to match personal identifiers (names, date of birth, and post code) with NHS personal identifiers, and returned individually-matched educational performance records. The potential linkage biases using this process were evaluated by comparing socio-demographic and clinical characteristics between linked and unlinked SLaM cases. Methods to mitigate these biases and their impact on an important clinical factor-educational association (ICD-10 Axis One mental disorder and school attendance) were explored using linkage probability weighting and adjustment. Results: Governance challenges included developing a research protocol for data linkage which met the legislative requirements for both section 251 of the NHS Act 2006 and The Education (Individual Pupil Information) (Prescribed Persons) (England) Regulations 2009(2). From a total 35,509 individuals referred to SLaM, 29,278 were matched to NPD school attendance records representing a linkage rate of 82.5%. There were significant differences in sociodemographic, clinical and administrative characteristics between groups linked and not linked to school data. For example, children with a recorded ICD-10 mental disorder were more likely to have linked records compared to those without ICD-10 disorder [adjusted Odds Ratio (aO.R) 1.11, 95% C.I 1.04-1.18]. Groups with a reduced likelihood of linkage included those first presenting to services in late adolescence (aO.R 0.67, 95% C.I 0.59- 0.75) or having NHS address data recorded outside school census timeframes (aO.R 0.15, 95% C.I 0.14-0.17). No significant differences were found in linkage rates between children in the lowest and highest quartiles of deprivation (aO.R 1.03(0.92-1.15). ICD-10 mental disorder remained significantly associated with persistent school absence (aO.R 1.13, 95% C.I 1.07- \1.22) after adjustments for linkage error. Conclusions: It is feasible to link routinely collected education and health for most school aged children and adolescences at an individual level. However current linkage methods can introduce biases, with older groups who present to clinical services being less likely to be captured. Possible biases due to linkage error can affect risk-factor outcome associations and need to be addressed when analysing and interpreting results. Funding: Medical Research Council Fellowship (JD); the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (J.D, R.H, M.H, R.S, A.J, R.L, H.S, M.B). Psychiatry Research Trust Peggy Pollak Fellowship (J.D); ESRC Administrative Data Research Network (R.G, TM), NIHR Child Policy Research Unit (R.G, Jess D) Publications: 1.

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Downs J, Ford T, Stewart R, Shetty H, Little R, Jewell A, Broadbent M, Deighton J, Mostafa T, Gilbert R, , Hotopf M, Hayes RD. (2018). Methods to linking education, social care and electronic health records for children attending mental health services BMJ Open (under review) Downs J, Gilbert R, Hayes RD, Hotopf M, Ford T. (2017). Linking up data to plan and improve mental health services for children in England. Archives of Diseases in Childhood, 102: 599-602

Community and School-based Intervention

Evaluation of a body satisfaction programme “Happy Being Me”: Delivery in schools by clinicians and teachers

Investigators: Dr Catherine Stewart, Dr Elizabeth Goddard, Ziba Cakir & Richard Hall National & Specialist Child and Adolescent Eating Disorder Service, South London and Maudsley NHS Foundation Trust.

Lay Summary: The Child and Adolescent Eating Disorder Service (CAEDS) is running a programme called “Happy Being Me” for some of the children in Year 7. Happy Being Me is designed to help children feel more satisfied with their body image and to help develop a positive and supportive class environment in relation to peer conversations about appearance and valuing each other’s other qualities. It has had good results in Australia and with Year 6 children in the UK, and is now being offered to Year 7 in South East London. This training is being offered by the NHS because body dissatisfaction is linked with young people feeling distressed and engaging in unhealthy behaviours to manage their appearance. We are running a study to measure the impact of the programme when it is delivered by teachers and clinicians on some of the factors that are linked to body dissatisfaction. These include making comparisons with other people, teasing people, talking a lot about appearance and trying to look like people in magazines and on TV. We will also look at the impact on self-esteem, body satisfaction and on attitudes to eating. It is important to test out how effective the programme is in the UK so that it can be offered to more schools and children if it is found to be as helpful here as it has been in Australia. We will be comparing outcome measures from young people who take part in the classes with a control group that doesn’t receive the classes, and will then compare young people who have the classes delivered by teachers with those who have it delivered by NHS staff. We will be comparing the effects to see whether it makes a difference who delivers the programme to the children. We predict that delivery by teachers will be as effective as delivery by clinicians. These results will be used to inform further training of teachers in other schools so that as many young people as possible can experience the programme. State of Progress: Ongoing Abstract: Background: This project is evaluating the delivery of a school-based intervention, Happy Being Me (HBM; Richardson & Paxton, 2010) delivered to whole classes in Year 7 by clinicians and teachers. HBM targets the risk factors for body dissatisfaction. Body dissatisfaction is associated with immediate distress and is a risk factor for the development of depressive symptoms and low self-esteem (Paxton et al., 2006), clinical eating disorders (Stice, Marti, & Durant, 2011), becoming overweight and obese (Haines et al 2010), as well as other difficulties. HBM targets individual psychological risk factors for body dissatisfaction, internalisation of the thin media body ideal, body comparisons, self-esteem and the peer environment risk factors of appearance conversations and weight related teasing (Richardson & Paxton, 2010, Bird et al, 2013). Happy Being Me (Paxton & Richardson, 2010) is a manualised school-based body image intervention programme delivered over 6 sessions to whole classes of 11-12-year old boys and girls. It targets internalisation of the thin ideal, body comparison, body teasing and appearance related conversation in order to facilitate a supportive peer environment and improved body image. Effectiveness of the programme has been demonstrated in Australia (Richardson & Paxton, 2010) and in a younger population in the UK (year 6; Bird et al., 2013). To date the Happy Being Me programme has been evaluated as delivered by therapists and researcher as external facilitators. It is not known whether the 171

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effectiveness of the programme would be maintained by delivery by school staff known to the students and who do not have professional training in areas relevant to mental health/eating disorders/body image. However, the programme is made freely available by the developers, and specific qualifications are not required to deliver it. This study aims to ascertain whether efficacy in the UK is comparable to that demonstrated by intervention developers in Australia, and whether the intervention remains effective when delivered by teachers in “real world” conditions. The demand for the programme from schools has outstripped the clinics capacity to provide it and ascertaining whether teacher delivery results in comparable changes will inform the wider dissemination and use of the programme. Aims/Objectives: (1) To measure the impact of HBM on a series of factors theoretically linked to the development of body dissatisfaction. We hypothesise that the intervention will increase self-esteem and body satisfaction, decrease appearance teasing, appearance comparisons and appearance conversations and reduce the internalisation of sociocultural appearance ideals. (2) To measure the maintenance of this effect 3 months after the end of the programme. (3) To evaluate whether outcomes are comparable when HBM is delivered by teachers. Method: This study is a non-randomised controlled evaluation of clinical and teacher delivery HBM. Self-report questionnaire data from 552 Year 7 students (boys and girls) across seven different schools is being collected across the three arms of the study (control, clinician delivered, teacher delivered). The project has two stages: Stage 1: To replicate London schools the findings of the programme developers in Australia (Richardson

& Paxton, 2010) that HBM reduces body dissatisfaction in classes of that receive the intervention compared to control classes that do not, and that these findings are maintained at three month follow up. Stage 2: To evaluate in a non-inferiority comparison whether outcomes are comparable when HBM is

delivered by school staff. Results: Preliminary data from the controlled trial suggests that those in the HBM group show significantly higher body satisfaction after the intervention compared to control groups (F = 4.17, p = .042, ƞ² = .01). Data collection is ongoing for clinical and teacher-led groups, and for follow up. Conclusion: The results of this study will demonstrate whether Happy Being Me in its current format, delivered by clinicians or teachers, is an effective addition to the school curriculum to support students’ emotional wellbeing. We anticipate data collection will be completed summer 2018. Funding: Own account Publications: Pending

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Service evaluation of a cognitive behavioural 100 CUES-Ed: early mental health intervention for whole classes of primary school children Investigators: Dr Debbie Plant1, Dr Anna Redfern1, Polly Snowdon1, Karen McIlwain1, Dr Sophie Browning1 & Dr Suzanne Jolley2 1 Children and Adolescent Mental Health Services Clinical Academic Group, South London and Maudsley NHS Foundation Trust; 2 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL).

Lay Summary: CUES-Ed, designed and delivered by Clinical Psychologists and Cognitive Behaviour Therapists from South London and Maudsley NHS Foundation Trust, is dedicated to promoting mental health and improving the emotional wellbeing of primary school aged children. Our innovative eight-session programme is delivered to whole classes as part of their normal school day. We teach children fundamental skills in emotional literacy and self-care and equip them with practical cognitive strategies and simple but effective behavioural techniques to help manage difficulties. The approach is rooted in evidence-based cognitive behavioural therapy (CBT) and uses visually striking and recognisable characters, hands-on activities, colourful workbooks and an interactive website to make abstract concepts more concrete and memorable and to facilitate learning and retention. We promote flexible and adaptive responses to difficulties, including self-regulation as well as supportseeking and recognising when extra help is needed - encouraging children to learn the skills that can help build their resilience from an early age. The project has been running in schools across London Boroughs since 2014, working with over 3500 children. We are committed to ongoing evaluation and ask all children and teachers to complete outcome measures before and after the intervention. Preliminary service evaluation shows high rates of overall acceptability, alongside improvements in well-being and emotional/behavioural problems for vulnerable children (those who report poor well-being or emotional or behavioural difficulties to begin with). Abstract: Our school-based cognitive behavioural early intervention programme is designed to engage whole classes in how to look after themselves and to improve wellbeing and emotional/behavioural difficulties, particularly for vulnerable children who have not been well-served by similar interventions to date. We conducted a mixed methods service-based evaluation. Qualitative feedback suggested psychoeducational improvements for the whole class following CUES-Ed and, for vulnerable children, well-being and emotional/behavioural problems improved. Background: As many as 1 in 10 school aged children will experience a mental health problem, with many more experiencing significant emotional difficulties which impact on learning, behaviour, social relationships, motivation and decision making, and increase vulnerability to mental health difficulties in adult life. Thresholds for child and adolescent services are increasing â&#x20AC;&#x201C; but children and young people need access to effective and acceptable early intervention to prevent difficulties escalating. Governmental recommendations increasingly highlight the importance of schools as an ideal provider of this early intervention support. Existing school-based approaches show limited improvements, particularly for vulnerable children. We conducted an in-service evaluation of CUES-Ed, our innovative and interactive school-based cognitive behavioural early intervention for whole classes of 7-10 year olds.

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Methods: Clinical Psychologists/CBT Therapists delivered CUES-Ed to 23 classes across schools in Southwark during the 2016/17 academic year. Teachers were present over the eight weekly, one-hour sessions. Pupils completed standardised self-report measures of wellbeing/distress (CORS; n=503), emotional difficulties (MMF-E; n=510) and behavioural difficulties (MMF-B; n=500) before and after CUES-Ed. Pupils (n=577) and teachers (n=27) also gave qualitative feedback on completion of the programme. Two classes (n=60) completed measures whilst waiting to participate in CUES-Ed, forming a naturalistic waitlist. Results: Thematic analysis of qualitative feedback indicated very good engagement, acceptability and positive subjective impact. The majority of children rated ‘all’ or ‘most’ of the time for their understanding (86%) and enjoyment (88%) of CUES-Ed. Feedback also suggested improvements for the whole class in emotional literacy and in understanding how to look after their mental health, with more normalising explanations for emotional responses to confusing or difficult experiences, and a wider repertoire of cognitive and behavioural coping strategies to help manage emotions. All teachers reported overall benefit to pupils from CUES-Ed. The majority rated ‘all’ or ‘most’ of the time for pupils’ enjoyment (85%) and understanding (93%). Vulnerable children (those scoring in the borderline/clinical range on each measure) improved on all three self-reported measures with medium pre-post within-subject effect sizes – and greater change following CUES-Ed compared to the waitlist with small between-group effects (Table 3). Conclusion: Feedback indicates that CUES-Ed is accessible and well-received and that we have been successful in creating a fun, engaging and useful resource from which children feel they can learn. Service evaluation also suggests that CUES-Ed has particular potential to improve outcomes for vulnerable children. Further controlled evaluation is now indicated. Funding: CUES-Ed was established using routine Trust funding. Delivery was commissioned by the London Borough of Southwark. Publication:

Redfern A*, Jolley S*, Browning S, Bracegirdle K & Plant D. CUES-Ed: An in-service evaluation of a new universal cognitive behavioural early mental health intervention programme for primary school children. Submitted to Child & Adolescent Mental Health. *joint first authors

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Table 3. Change on standardised measures for those scoring in borderline/clinical range

Group

CORS

CUES-Ed

Pre

Post

t (df),

Mean

(pre-post)

227

(SD) 22.98

(SD) 26.56

(between group)

-5.99 (226),

0.46

0.23

(6.68) 25.42

(8.64) 27.15

<0.01 -1.00 (25),

0.21

144

(5.52) 11.94

(9.31) 9.99

0.33 6.80 (143),

0.65

(2.45) 11.56

(3.33) 10.35

<0.01 1.66 (16),

0.45

100

(1.55) 7.43

(3.08) 6.04

0.12 5.88 (99),

0.65

(1.46) 8.09

(2.44) 7.07

<0.01 1.16 (14),

0.34

(1.79)

(3.49)

0.26

Wellbeing/ Waitlist

distress MMF-E

CUES-Ed

Emotional difficulties MMF-B Behavioural difficulties

Waitlist CUES-Ed Waitlist

0.25

0.16

Abbreviations. CORS= self-report measures of wellbeing/distress, MMF-E= self-report measures of emotional difficulties, MMF-B= self-report measures of behavioural difficulties, CUES-Ed = coping with unusual experiences for children study, n = number of participants, SD= standard deviation, df = degrees of freedom, p = statistical significance threshold, d = effect size

101 School-based early intervention for anxiety and

depression in older adolescents: A feasibility randomised controlled trial of a self-referral stress management workshop programme (“DISCOVER”)

Investigators: Dr June Brown1, Dr Irene Sclare2, Dr Daniel Stahl3 & Dr Daniel Michelson1 1 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London (KCL); 2 Child and Adolescent Mental Health Services Clinical Academic Group, South London and Maudsley NHS Foundation Trust; 3 Department of Biostatistics and Health Informatics, IoPPN, KCL.

Lay Summary: This RCT study explored the impact on “hard to reach” teenagers with anxiety and depression of the DISCOVER programme, when delivered within schools. Mental health outcomes were compared with students on a waitlist for DISCOVER. DISCOVER is an innovative mental health intervention, based on CBT principles, that was developed with teenagers and uses a range of multi-media methods to make the interventions acceptable and accessible. The aim of DISCOVER is to reach and treat young people who are unlikely to access usual CAMHS care, and uses telephone follow up to sustain participants’ progress. The study included qualitative interviews with students and teachers as well as analysis of mental health and wellbeing outcomes prior to the group workshop, and at the three-month follow up. 175

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State of Progress: Completed in 2015 Abstract: Methods: To assess the feasibility of a brief school-based psychological intervention, the DISCOVER workshop programme, for self-referred adolescents aged 16-19 years, a single-blind two-arm cluster randomised controlled trial (RCT) was conducted in 10 inner-city schools with block randomisation of schools. The intervention comprised a one-day CBT â&#x20AC;&#x153;How to Manage Stress and Worryâ&#x20AC;? programme with telephone follow-up (DISCOVER) compared with a waitlist control condition. Schools were the unit of allocation, minimising the potential for contamination between trial arms; students were the unit of analysis. Primary outcomes were self-reported depression and anxiety. Outcomes were measured for both arms at baseline and three-month follow-up. Ethical approval was obtained from the Camberwell St Giles National Research Ethics Service (Ref: 14LO1416). The design and outcomes followed the published protocol (Michelson et al., 2016). Results: A total of 155 students enrolled and 142 (91.6%) followed up after 3 months. Over 55% students were from ethnic minority groups. Intraclass correlations were low. Variance estimates were calculated to estimate the sample size for a full RCT. Preliminary outcomes were encouraging, with reductions in depression (d=0.27 CI-0.49 to -0.04, p=0.021) and anxiety (d=0.25, CI-0.46 to -0.04, p=0.018) at follow-up. Results support the feasibility of DISCOVER as a school-based, self-referral intervention with older adolescents in a definitive future full-scale trial (Trial no. ISRCTN88636606). Conclusion: This study demonstrates that the delivery and evaluation of self-referral DISCOVER workshop programme are feasible in schools. It provides the basis for a larger RCT, focussing on effectiveness and enabling sub-group analyses of intervention effects. Provided the phase III trial reports effectiveness and acceptability, the DISCOVER workshop programme could constitute a much-required source of accessible support for older adolescents. Funding: National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference PB-PG-0213-30072). Publications: Manuscript is submitted to Journal of Adolescence

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acceptability and feasibility of implementing a brief 102 The dialectical behaviour therapy (DBT) skills group in pupil referral units (PRU) Investigators: Lucie Gallagher1,2, Dr Lorna Taylor1, Dr Emmie Neophytou1 & Dr Kate Johnston1,2 1 National & Specialist CAMHS for Adolescent At-risk and Forensic Service, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London (KCL). Lay Summary: There has been a recent expansion in schools-based mental health interventions as a platform for the promotion of mental wellbeing, and the prevention and treatment of psychological difficulties. Government reports have highlighted the lack of mental health support in alternative education provisions, where the students have a high level of need. There is an emerging evidence base to support the feasibility, acceptability and effectiveness of Dialectical Behaviour Therapy (DBT) groups as a standalone intervention in education settings to address the emotional and behavioural difficulties of young people. This study will aim to extend this evidence base by assessing the acceptability and feasibility of implementing a DBT skills group intervention in a unique setting, a PRU in the UK, its effectiveness improving primarily behavioural outcomes, and examining the role of emotion regulation as a possible mechanism of change. State of Progress: Ongoing Abstract: Background: Dialectical Behaviour Therapy (DBT) has a promising emerging evidence base in an adolescent population. The skills component of DBT has received increasing attention as a standalone intervention to assist young people in developing effective strategies to manage their emotions, behaviours and relationships. Schools are being recognised as a unique platform to access young people who may benefit from, but do not typically present, in mental health services. Pupil Referral Units (PRUs), for young people who have been excluded from mainstream schools, have a high prevalence of young people with emotional and behavioural problems. DBT may be a suitable intervention to meet the needs of these young people due to its focus on emotion dysregulation. This uncontrolled pilot study aims to evaluate the acceptability and feasibility of running a brief DBT skills group in a PRU, investigating changes in a range of outcome and process measures Methods: Participants will be students at a PRU in Lambeth, London. They will be mixed-gender Year 8 to Year 11 students (aged 12 – 16 years). The target sample size is 16-25 participants. The only exclusion criteria will be levels of aggression that would put others’ safety at risk, as identified by school staff. The six-session programme will draw on skills from each of the four DBT modules: Mindfulness: Mindfulness will be introduced in the initial session and then each session thereafter will

begin with a mindfulness exercise. The concept of the three states of mind (reasonable mind, emotion mind and wise mind) will be explored. Emotion Regulation: These sessions will teach young people how to check the facts of the situation,

to work out whether their emotions are justified or unjustified, and then to use problem solving or opposite action to change the emotion respectively.

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Distress Tolerance: These sessions will focus on crisis survival skills (e.g. pros and cons of acting on urges,

self soothe strategies, paired muscle relaxation etc.) and acceptance (for when we cannot change the situation that is causing distress). Interpersonal Effectiveness: These sessions will teach young people how to how to get what they want or

need from a relationship, how to say “no”, how to keep or build the relationships that they want and how to end destructive ones. Results: Data collection currently underway and the project is running in a local PRU in Lambeth. Conclusion: N/A as project is ongoing. Funding: Funding from King’s College London Doctorate in Clinical Psychology programme. Publications: Pending

programme: Students’ views of a school-based 103 DISCOVER CBT workshop and experiences of waiting for a service Investigators: Aisling Roche & Dr Tessa Crombie National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust

Introduction and Background: A recent systematic review of school-based mental health programmes utilising RCT designs revealed these programmes can be effective in reducing anxiety and depression in young people (1). However, to date there has been no study that has explicitly focused on the views and experiences of students assigned to the control condition of such school-based mental health programmes. Expectations for therapy effectiveness have been shown to be lower in control groups than in experimental groups (2). Other findings suggest that participants can feel disappointed at being waitlisted for an intervention whilst some people can derive motivation during the wait-period (3). Research capturing the views of young people assigned to control groups, in particular, wait-list control groups has important clinical implications. It can give us a valuable insight in to the course of their presentation during the wait period, their use of coping strategies and their expectations of the planned intervention. Abstract: This study aimed to evaluate a CBT-based workshop for young people and expand on our understanding of participants’ experiences of being assigned to a wait-list (WL) control group. Methods: 104 students from both the experimental (i.e. immediate treatment) and WL groups of a 1-day CBT based workshop (DISCOVER) completed a satisfaction questionnaire following completion of the workshop. Following this, 4 students assigned to the WL group attended a focus group.

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Results: (1) Questionnaire Data

53% from the immediate group and 45% from the WL groups stated they were very satisfied with the overall service they received from DISCOVER. 47% from the immediate group and 36% from the WL group stated that the workshop helped them greatly in dealing more effectively with their problems. 62% of the WL group reported that the workshop helped them somewhat in dealing more effectively with their problems. Figure 13. Participant ratings of the most useful techniques covered in the DISCOVER workshop

(2) Focus Group Data

The following themes emerged from student’s feedback of the wait- period Lack of Transparency: The length of the wait-period or when the workshop would be held was not

communicated to students “At one point, I thought it had been cancelled” (Yr. 12 Student). The rationale for waiting was also unclear as students were unsure why they completed two sets of questionnaires before receiving the workshop. Loss of interest: “I felt a bit disinterested in it. After the long wait, I felt like just dropping out” (Yr. 12

Student) and “Because we didn’t hear about it for such a long time, it put me off it a little bit”. (Yr. 13 Student). Timing of the Workshop: Competing demands due to upcoming exams meant March was a busy month and

some teachers were less supportive of their students attending during this time. Students reported a lack of transparency during the wait-period which resulted in a loss of interest. However, their satisfaction ratings after having received the workshop were very similar to those assigned to the immediate group. Service Recommendations Workshop Day:

More interactive delivery and a shorter workshop or spread workshop over 2 days. Wait-Period:

1. It is important that the DISCOVER team communicate workshop dates with students and teachers during the wait-period to retain interest and support. 2. Satisfaction questionnaires should be developed that capture the unique views of those students assigned to the WL Funding: This project was completed in part fulfilment of a Doctorate in Clinical Psychology. 179

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CBT for depressed adolescents: 104 Computerised Randomised controlled trial Investigators: Patrick Smith1,2, Dr Alex Robinson2, Dr Paul Abeles3, Prof Judy Proudfoot4, Dr Chrissie Verduyn3 & Prof William Yule2 1 National & Specialist CAMHS Anxiety & Traumatic Stress Clinic, Michael Rutter Centre, South London and Maudsley NHS Foundation Trust; 2 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), Kingâ&#x20AC;&#x2122;s College London (KCL); 3 Central Manchester University Hospitals NHS Foundation Trust; 4 Black Dog Institute, University of New South Wales.

Lay Summary: Depression is common in adolescence. Effective face to face therapies exist. However, most adolescents with depression are not able to access face to face therapy. This project made a novel computerised therapy for depression available in schools and valuated it in a randomised controlled trial. Results were promising. State of Progress: Completed Abstract: Background: Depression in adolescents is a common and impairing problem. Effective psychological therapies for depression are not accessed by most adolescents. Computerised therapy offers huge potential for improving access to treatment. Methods: Multi-site, schools-based, RCT of C-CBT compared to Waiting List, for young people (n= 112; aged 12-16 years) with significant symptoms of depression, using multiple-informants (adolescents, parents, teachers), with follow-up at 3 and 6 months. Results: Relative to being on a Waiting List, C-CBT was associated with statistically significant and clinically meaningful improvements in symptoms of depression and anxiety according to adolescent selfreport; and with a trend towards improvements in depression and anxiety according to parentreport. Improvements were maintained at follow-up. Treatment gains were similar for boys and girls across the participating age range. Treatment effect was partially mediated by changes in ruminative thinking. Teachers rated adolescents as having few emotional or behavioural problems, both before and after intervention. C-CBT had no detectable effect on academic attainment. In the month after intervention, young people who received C-CBT had significantly fewer absences from school than those on the Waiting List. Conclusion: C-CBT shows considerable promise for the treatment of mild-moderate depression in adolescents. Funding: Psychiatry Research Trust Publication:

Smith P, Scott R, Eshkevari E, Jatta F, Leigh E, Harris V â&#x20AC;Ś Yule W. (2015). Computerised CBT for depressed adolescents: Randomised controlled trial. Behaviour Research and Therapy, 73, 104-10.

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Notes

Department of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience Kingâ&#x20AC;&#x2122;s College London 16 De Crespigny Park London SE5 8AF https://www.kcl.ac.uk/ioppn/depts/cap

Design & illustrations by: Keith Hau