RESEARCH INSIGHT

RESEARCH INSIGHT Variation in health outcomes associated with childhood maltreatment: Social and physiological factors CW: su*cide mention, s*lf-h*rm mention

MADELINE KOMAR Honours Psychology, Neuroscience & Behaviour (Mental Health Specialization), Class of 2022, McMaster University komarm1@mcmaster.ca

ABSTRACT Maltreated children tend to experience worse health in adulthood. The physiological model of allosteric load helps to explain why maltreated children often experience adverse physical health outcomes including stroke, cancer, and diabetes in adulthood. However, since mental health and health behaviours vary depending on one’s social environment, understanding mental health and risky health behaviours among people who experienced childhood maltreatment requires integrating biological and psychosocial analyses. Among older survivors of childhood maltreatment, variation in mental health and health behaviours corresponds to variation in socioemotional adjustment. This variation in socioemotional adjustment corresponds to variation in parasympathetic nervous system functioning as measured by respiratory sinus arrhythmia (RSA).Clinicians could potentially use RSA as a screening tool to identify maltreated children whose poor socioemotional adjustment puts them at greater risk of adverse health outcomes in adulthood.

INTRODUCTION Chronic childhood stress predicts poor physical health in adulthood, increased participation in risky health behaviours, and worse mental health.1 Child maltreatment refers to emotional, physical, and sexual abuse as well as experiences of neglect, all of which cause chronic stress.2

Negative physical health outcomes among survivors of childhood maltreatment can be explained using the biological model of allosteric load. Allosteric load refers to the cumulative effect of having a chronically active physiological stress response, for instance, “wear and tear” of major organ systems.3 Exposure to stressors triggers the physiological stress response causing the sympatho-adrenomedullary and hypothalamicpituitary-adrenal (HPA) axis to release chemical signals that help prepare the body for fight, flee, or freezing responses.1 Blood vessels constrict to increase blood pressure, heart and respiration rates increase to maximize oxygen supply, lipolysis breaks down adipose tissue to increase blood sugar, and the immune system is suppressed.1 Normally, the HPA axis is inhibited via a negative feedback loop and the child can relax once the threat has passed.1 Maltreated children however, are exposed to more stressors over longer periods of time, resulting in chronic activation of the physiological stress response systems. Since the physiological stress response is energetically costly, chronic activation strains bodily organs to increase allosteric load. The effects of the additional allosteric load accumulate over time, contributing to poorer health outcomes in adulthood. The concept of allosteric load can be used to explain the positive correlation between levels of chronic stress in childhood and the prevalence of physical health problems such as heart disease, cancer, chronic bronchitis, and diabetes in adulthood.1 Risky health behaviours during adolescence may exacerbate the strain caused by allosteric load.1,3

Adverse childhood experiences are significantly associated with risky health behaviours such as illicit drug use, cigarette smoking, and reckless self-endangerment, as well as more frequent mental health problems including alcoholism and depression.1,4,5 However, risky health behaviour and mental health outcomes vary among adults who experienced child maltreatment, which may be the result of differing socioemotional adjustment during childhood.5 Examining how social situations and physiological features interact over the course of development to produce different health behaviours among maltreated children is essential for effective intervention programs.

RESEARCH DESIGN The objectives of this review are to demonstrate the relationship between poor socioemotional adjustment and risky health behaviours among maltreated children by exploring the connection between parasympathetic nervous activity and socioemotional adjustment. Additionally, this review further explores if respiratory sinus arrhythmia (RSA) moderates the relationship between childhood maltreatment and poor socioemotional adjustment.

Research article selection began with a brief review of the works produced by researchers at the Child Emotion Lab at McMaster University. The Child Emotion Lab examines the relationships between personality traits (primarily shyness), early life environment, and social behaviour. From there, other articles were selected using Google Scholar, PubMed, and Scholars Portal. Given the interdisciplinary nature of the research, a broad array of keywords were used, including “respiratory sinus arrhythmia”, “childhood maltreatment”, “socioemotional adjustment”, “early adversity”, “self-regulation”, “mental health”, “resilience”, and “emotional flexibility”.

MEASURING SOCIOEMOTIONAL ADJUSTMENT Socioemotional adjustment refers to the quality of an individual’s interaction with their environment. Researchers studying socioemotional adjustment examine how children’s traits affect the social situations they experience, and how social situations evoke a variety of responses in different children. For example, a child with a negatively reactive temperament tends to interpret neutral stimuli as threatening, and has disproportionately intense reactions of distress or anger. This temperamental style contributes to aggressive responses with little provocation, which hinder the development of positive social relationships. Researchers gauge socioemotional adjustment in children by examining social outcomes such as peer rejection, reputation, and social network strength.6 For the purposes of this review, poor socioemotional adjustment refers to lacking positive social engagement and exhibiting intense negative reactivity.

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Topitzes J, Mersky JP, Reynolds AJ. Child maltreatment and adult cigarette smoking: A long-term developmental model. J Pediatr Psychol. 2009; 35(5): 484–98. Available from: doi:10.1093/jpepsy/jsp119.

Haskett ME, Nears K, Ward CS, McPherson AV. Diversity in adjustment of maltreated children: factors associated with resilient functioning. Clin Psychol Rev. 2005;26:796-812. Available from: doi:10.1016/j.cpr.2006.03.005.

Gülay H, Önder A. A study of social–emotional adjustment levels of preschool children in relation to peer relationships. Educ. 2012; 41(5): 514-22. Available from: doi: 10.1080/03004279.2011.609827.

Yoon S, Howell K, Dillard R, Shockley McCarthy K, Napier T, Pei F. Resilience following child maltreatment: definitional considerations and developmental variations. Trauma Violence Abuse. 2019;15:24-8. Available from: doi: 10.1177/1524838019869094.

Taussig HN. Risk behaviors in maltreated youth placed in foster care: a longitudinal study of protective and vulnerability factors. Child Abuse Negl. 2002;26(11):1179-99. Available from: doi:10.1016/s0145-2134(02)00391-5.

Karatekin C, Ahluwalia R. Effects of adverse childhood experiences, stress, and social support on the health of college students. J Interpers Violence. 2020;35(1-2):150-72. Available from: doi:10.1177/0886260516681880.

Afifi TO, MacMillan HL. Resilience following child maltreatment: A review of protective factors. Can J Psychiatry. 2011;56(5):266-72. Available from: doi:10.1177/070674371105600505.

Gratz KL. Risk factors for deliberate selfharm among female college students: the role and interaction of childhood maltreatment, emotional inexpressivity, and affect intensity/reactivity. Am J Orthopsychiatry. 2006;76(2):238-50. Available from: doi:10.1037/0002-9432.76.2.238.

Waugh CE, Thompson RJ, Gotlib IH. Flexible emotional responsiveness in trait resilience. Emotion. 2011;11(5):1059-67. Available from: doi:10.1037/a0021786.

Kashdan TB, Rottenberg J. Psychological flexibility as a fundamental aspect of health. Clin Psychol Rev. 2010;30(7):865–78. Available from: doi:10.1016/j.cpr.2010.03.001.

Porges SW. Orienting in a defensive world: Mammalian modifications of our evolutionary heritage: A polyvagal theory. Psychophysiology. 1995;32(4):301–18. Available from: doi: 10.1111/ j.1469-8986.1995.tb01213.x.

Marcovitch S, Leigh J, Calkins SD, Leerks EM, O’Brien M, Blankson AN. Moderate vagal withdrawal in 3.5-yearold children is associated with optimal performance on executive function tasks. Dev Psychobiol. 2010;52(6):603–8. Available from: doi:10.1002/dev.20462.

Skowron EA, Cipriano-Essel E, Gatze-Kopp LM, Teti DM, Ammerman RT. Early adversity, RSA, and inhibitory control: Evidence of children’s neurobiological sensitivity to social context. Dev Psychobiol. 2013;56(5):964–78. Available from: doi:10.1002/dev.21175.

17. Hassan R, Poole KL, Schmidt LA. Revisiting the double-edged sword of self-regulation: Linking shyness, attention shifting, and social behavior in preschoolers. J Exp Child Psychol. 2020;196. Available from: doi:10.1016/j.jecp.2020.104842. RISKY HEALTH BEHAVIOURS AND

VARIATION IN SOCIOEMOTIONAL ADJUSTMENT Socioemotional adjustment varies among children exposed to maltreatment. Positive social engagement is generally associated with improved health among maltreated youth.7 For maltreated youth placed in the foster care system, differences in the quality of peer relationships among the youth accounted for up to 19% of the variance in their likelihood to engage in risky behaviours, including unsafe sex, substance abuse, and suicidal behaviours approximately one year later.8 Similar effects have been observed in college students, suggesting that having a strong social network and positive social engagement protects against adverse health outcomes among people with a history of maltreatment throughout their life.9

Maltreated youth with balanced life outlooks engage in risky health behaviours less often than their more negatively reactive peers.5,10 Specifically, higher levels of negative emotional reactivity were positively correlated with frequent self-harming behaviour among female survivors of childhood maltreatment.11 The ability to respond flexibly to emotional stimuli, rather than react with blanket negativity, has been positively associated with resilient functioning in a variety of contexts.12,13

SYSTEM AND SOCIOEMOTIONAL ADJUSTMENT The parasympathetic nervous system has a calming, inhibitory influence on the body. Under normal conditions, this system helps maintain homeostasis by inhibiting the sympathetic nervous system, preventing a chronic stress response. For example, the inhibitory influence of the parasympathetic nervous system keeps heart rate low in the absence of danger. When a threat is detected, the parasympathetic nervous system withdraws its inhibitory effect, allowing heart rate to increase. The sympathetic nervous system activates, increasing the heart rate further.1,14

RSA is used to index parasympathetic nervous system activity. Through indexing parasympathetic nervous system functioning, RSA informs researchers about one’s ability to respond flexibly to social situations.14 Baseline RSA is positively associated with executive functioning, emotional regulation, and attentional shifting.15-17 The parasympathetic nervous system influences heart rate via the 10th cranial nerve and RSA measures how heart rate varies with respiration. Thus RSA indirectly indexes PNS activity.14,17 High baseline RSA reflects effective parasympathetic nervous system functioning and the ability to respond flexibly to stress, while low baseline RSA reflects a lack of flexibility because there is more lability for change in the event of encountering environmental stressors. Because high levels of baseline RSA suggest more parasympathetic activation, parasympathetic nervous system functioning should decrease in response to environmental stressors. Since the parasympathetic nervous system is operating at a relatively low level among children with low baseline RSA, a smaller increase in arousal occurs in response to a stressor (see Figure 1).14-16,18 THE PARASYMPATHETIC NERVOUS

RSA AS A PREDICTOR OF SOCIOEMOTIONAL ADJUSTMENT IN MALTREATED CHILDREN Differences in baseline RSA correspond to differences in negative reactivity and social network quality. Baseline RSA is negatively associated with negative reactivity throughout development. One study measured baseline

FIGURE 1. Higher baseline RSA indicates higher baseline parasympathetic nervous system activation. People with higher baseline RSA then have more room to maneuver when responding to threats; the magnitude of the difference between their baseline state and their state of emergency is greater for people who have low baseline RSA (A>B). Thus, people with high baseline RSA have more flexibility to respond to environmental stressors.

RSA among a sample of maltreated adolescent girls, and used baseline RSA to predict levels of neuroticism over one year. Neuroticism is a personality trait associated with blanket negative reactivity; neurotic individuals tend to interpret neutral stimuli as negative and struggle to regulate their emotions. This study found that baseline RSA predicted neuroticism trajectories over the course of the year, such that neuroticism increased among girls with low baseline RSA, and remained low and stable among girls with high baseline RSA.19

Baseline RSA has been directly linked to social engagement in the general population, and this relationship likely exists among people who experienced childhood maltreatment.20 However, differences in RSA correspond to differences in aggressive behaviour among maltreated youth aged 6 to 19, as behaving aggressively makes it harder for a child to make friends.21,22 Anti-social maltreated children have pre-established aggressive behaviour patterns by the time they enter school, suggesting that aggressive behaviours contribute to peer rejection, rather than the reverse.23 High baseline RSA may act as a buffer for aggressive behaviour.22 The effects of RSA in moderating aggressive behaviour are especially significant considering aggressive behaviour contributes to peer rejection during childhood and into adolescence.23 Given that adolescent peer relationships buffer against mental illness and risky health behaviours among survivors of maltreatment, RSA may be an effective screening tool to identify children at risk of adverse developmental trajectories.7-10

CONCLUSIONS Individual differences in parasympathetic activity moderate the effect of childhood maltreatment on socioemotional adjustment. Differences in socioemotional functioning can then partially explain differences in health-risk behaviours (see Figure 2). RSA should be considered as a tool for predicting socioemotional adjustment in maltreated children. If physicians can identify which maltreated children are most likely to struggle socially, physicians can use targeted interventions to improve socioemotional adjustment among those children, thereby reducing the risk of mental health issues and risky health behaviours. Further research should assess the reliability and validity of RSA in directly predicting future risky health behaviours and mental health outcomes of maltreated children.

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23. Hassan R, MacMillan HL, Tanaka M, Schmidt LA. Psychophysiological influences on personality trajectories in adolescent females exposed to child maltreatment. Dev Psychopathol. 2020;32(4):1390-401. Available from: doi:10.1017/S0954579419001342.

Geisler FCM, Kubiak T, Siewert K, Weber H. Cardiac vagal tone is associated with social engagement and selfregulation. Biol Psychol. 2013;93(2):279-86. Available from: doi:10.1016/j.biopsycho.2013.02.013.

Gordis EB, Feres N, Olezeski CL, Rabkin AN, Trickett PK. Skin conductance reactivity and respiratory sinus arrhythmia among maltreated and comparison youth: Relations with aggressive behavior. J Pediatr Psychol. 2010;35(5):547–58. Available from: doi:10.1093/jpepsy/jsp113.

Fanti KA, Henrich CC, Brookmeyer KA, Kuperminc GP. Aggressive behavior and quality of friendships. J Early Adolesc. 2008;29:826-38. Available from: doi:10.1177/0272431609332819.

Bolger E, Patterson CJ. Developmental pathways from child maltreatment to peer rejection. Child Dev. 2001;72(2):549-68. Available from: doi:10.1111/1467-8624.00296.

REVIEWED BY: DR. LOUIS SCHMIDT & RAHA HASSAN

Raha Hassan is a Ph.D. candidate in the Department of Psychology, Neuroscience and Behaviour. Her research interests center around the relation between children’s self-regulation and their temperament.

Dr. Louis Schmidt is a professor in the Department of Psychology, Neuroscience and Behaviour, as well as a Science Research Chair in Early Determinants of Mental Health. His research interests focus on how temperment and early life experiences can influence the relationship between brain development and behaviour, as well as the processes associated with typical and less typical development.

EDITED BY: NICK TELLER & TAAHA HASSAN

INTERVIEW SPOTLIGHT

DR. SHEILA SINGH

Photo Credit: Unknown

The Dynamics of Brain Tumors

MICHAL MOSHKOVICH1 & SOPHIE ZARB2 1Bachelor of Health Sciences (Honours), Class of 2023, McMaster University 2Bachelor of Health Sciences (Honours), Class of 2022, McMaster University

Dr. Sheila Singh is a Pediatric Neurosurgeon at McMaster Children’s Hospital, a Professor of Surgery and Biochemistry at McMaster University, and a Canada Research Chair in Human Cancer Stem Cell Biology. She is also a Principal Investigator in the Stem Cell and Cancer Research Institute at McMaster University and the Director of the McMaster Surgeon Scientist Program. Her research has been dedicated primarily to applying a developmental neurobiology approach to the study of human brain tumours.

WHAT INSPIRED YOU TO PURSUE A CAREER PATH IN PEDIATRIC NEUROSURGERY AND STEM CELL AND CANCER RESEARCH?

So, I think I knew for a long time, since I was a girl, that I wanted to be a doctor and was mostly inspired by family members. My mother was a nurse and my father was a doctor and so the whole sort of caregiving aspect really appealed to me. When I went to medical school, I had an abiding interest in the brain. It started because my father, who is a psychiatrist, had all kinds of books on psychotherapy, and they were the only books that were available in his library. Mostly, they were all Sigmund Freud and stuff like that, so I started reading psychology and became fascinated by how little we know about the brain. When I got to medical school, I knew I wanted to do something related to the brain and did electives in everything that had the word “neuro” in front of it. So, the reason I chose neurosurgery is because, out of all of the fields which were intellectually interesting and cognitively gratifying, I found only neurosurgery had that sense of activism where you threw yourself into a cause where someone was very sick and you were actually able to do something about it. In neurology, I loved the diagnostic process, the whole localizing the lesion and finding out where the central nervous system was injured based on someone’s presentation. But, it was depressing because, very often, you’d say, “Oh, you have a neurodegenerative disorder for which there’s no known cure and I don’t have any medical treatments for you”. That was too passive for me. So, I think it was really just the difference between passive and active that made me choose neurosurgery because that just suits my personality. When I was a teenager, I was kind of a social activist and I always wanted to pick up a cause and protest so I think neurosurgery suited me personally because of the activism. Having said that, when I chose neurosurgery in medical school, I didn’t pick it lightly; I really tested myself, trying to find out what I enjoyed the most. Once I realized it was neurosurgery, I wanted to make sure that I was able to keep up with the demands of the profession. So, I did enough electives to have experience in it, to know that I enjoyed the pace and the demands of the lifestyle. That’s another important thing: just because you like something, the next question is, am I well suited for this? Then, the final thing is that you know at the end of everything in medical school, this was the only thing I loved. It’s almost as if when you love something like that, then it chooses you, it’s not like you chose it. I couldn’t imagine myself doing anything else.

I set up a lab at the McMaster Stem Cell and Cancer Research Institute in 2007 when I joined here as a pediatric neurosurgeon. It was really quite an amazing fit for me because they started the institute in 2006, and my PhD was involved in the characterization of the population of cancer stem cells and brain cancer. So, it was a perfectly named institute for me. My lab applies a developmental neurobiology and stem cell biology approach to the study of brain cancer. We don’t study cancer in isolation. We study cancer, knowing that it’s a dynamic process, and we’re trying to imagine what could be the conversion that happens in cancer from a normal state to an abnormal state. So, we always study cancer in comparison to normal tissues, which is a slightly different approach. Another mandate of the institute is that we focus on human model systems, which are much more challenging and difficult to develop. We study all human normal neural stem cells in comparison to human brain cancer stem cells. The reason that I think you need an institute to accomplish something like that is because modeling those systems is not only intense in terms of the experience and training required, but it’s also very expensive, so it’s a lot better if you have a group of researchers who can focus in this area and then share infrastructure together. That’s why an open concept model of the institute was also really appealing with a shared lab space. It sort of promotes team-building as well.

WE WERE WONDERING IF YOU COULD ELABORATE ON THE PATH THAT YOUR RESEARCH TOOK TO BRING YOU TO YOUR GROUNDBREAKING DISCOVERY OF THE BRAIN TUMOUR-INITIATING CELLS.

When I spoke to many other people who made important discoveries or seminal discoveries, what you find is that most of them are serendipitous. So, almost everything that turns into a discovery is something that people have observed before. They’ve just never made the connection of what the observation could imply. So, for me, I wasn’t the first person to visualize these floating spheres of cells in a dish when we placed brain tumor cells into culture without serum. I’m sure I wasn’t the first person to observe that there were lovely cells growing in these spheres. However, I think we may have been the first people to realize what those spheres implied because the sphere is just a floating colony of all the cells that are present in a stem cell hierarchy. So, basically a sphere arises from a single stem cell that divides and then gives rise to all this divergent progeny, all of which clump together and float around in this sphere. As a result, I think we realized, when we saw that, that this meant there were stem cells in brain cancer. So, not that it was a novel observation, but simply that we interpreted it in such a way that led us to that discovery.

ARE THERE ANY NEW TECHNOLOGIES ON THE HORIZON THAT MIGHT BE ABLE TO FURTHER AID IN THE ANALYSIS OF BRAIN TUMOR CELLS, ESPECIALLY SINCE YOU HAVE MENTIONED THE DYNAMIC NATURE OF TUMOR GROWTH?

I think one thing is recognizing that cancer is a dynamic system. I think modeling how cancers form, and its heterogeneity, both at a cellular and a genetic level, as well as from a spatial and temporal perspective is important. So building model systems that capture how cancers evolve over time or tumor evolution is a theme that’s been really powerful. This relies on capturing tissue from patients at different time points throughout their treatment. So not just basing all your knowledge on the treatment-naive biopsy of the patient’s cancer at the beginning, but rather trying to survey the cancer through time and understand how the cells evolve and how genetic mutations evolve over time as well. So the whole field of intra-tumoral heterogeneity and apt cancer evolution has been of great interest. There’s been many tools that have been developed for things like lineage tracing where you follow cells through time, or DNA cellular barcoding where you drop a barcode library on cells at the beginning and then observe whatever manipulation you put the cells through. For example, you implant a tumor into a mouse and then you can track all the different barcodes through time and figure out which ones dropped out after therapy. You can try to figure out what cells are actually driving the tumor to recur or relapse. So, those are models and experimental systems that we’ve been using.

But, last year at the most recent Society for Neuro-Oncology meeting, the first technology that seems to be gripping everyone right now is single cell sequencing. So, everyone likes the idea of deconvoluting something down to its most basic building block and trying to understand what’s happening at a single cell level and there’s all kinds of new technologies in that regard. And then the second thing that everyone’s talking about is organoids. Organoids are like complex cellular systems. Imagine that we right now have cultures filled with spheres that are from a patient’s brain tumor, but now imagine if you could build a brain microenvironment using normal brain cells and then sort of graft the tumor into that and try to sort of recapitulate a more realistic model system of how the tumor may grow in the patient. These organoids are cultures where you can mix normal and cancer cells and try to establish a three-dimensional model of what may be happening in the patient. You can do that all in a dish, which is the appeal of it. So, I think those kinds of model systems have everyone excited right now. I don’t think they’re too close yet to what happens in patients, but they’ll get better.

WHAT DO YOU BELIEVE ARE THE NEXT STEPS FOR YOUR LAB OR FOR YOU AS A RESEARCHER-SCIENTIST?

We’re very excited in the Singh Lab about the prospect and the hope of immunotherapy because there have been some big breakthroughs with harnessing the immune system to treat cancers like blood cancers and melanoma. We’re hoping that some of those approaches can apply to brain cancer. It’s a big challenge because the brain is notoriously known for being an immunosuppressive environment. So, things can hide out in the brain and escape detection by the immune system and that’s possibly why brain cancers do so well. How do you somehow alert the immune system and notify the brain that there is something that needs to be dealt with? Trying to relieve that immunosuppression using things like new versions of checkpoint inhibitors that kind of wake up the immune system and uncover the tumors’ ability to evade immune detection is one option. Another option is developing direct targeted therapies like engineering T-cells to go after a tumor antigen that’s expressed on a brain cancer cell and then deploying them to go and attack the antigen. These are therapies that are not like your traditional chemotherapies, but rather, new therapies that are more specific but also may be more organic because they’re based on your own immune system.

INTERVIEW SPOTLIGHT DR. SUZANNE ARCHIE

EXPLORING PSYCHOSIS IN YOUTH CANNABIS USERS

ERIC ZHANG 1 & NURI SONG 2 1Bachelor of Health Sciences (Honours), Class of 2024, McMaster University 2Bachelor of Health Sciences (Honours), Class of 2022, McMaster University

Over the past two decades, the relationship between marijuana and youth usage has been evolving. Recent research suggests that marijuana use increases risk of psychosis, a state of impaired reality involving hallucinations, delusions, and thought disorganization. To explore such issues, we sat down with Dr. Suzanne Archie, an Associate Professor in the Department of Psychiatry and Behavioural Neurosciences and Clinical Director of the Cleghorn Early Intervention in Psychosis Program at St. Joseph’s Healthcare Hamilton. She is also a psychiatrist at the Peterborough Centre for Addictions Research and a Brain and Behaviour Subunit Planner for the Undergraduate Medical Education Program at McMaster University. Her research interests include early intervention for youth marijuana use and ethnic diversity in pathways to care for first episodes of psychosis. Presently, Dr. Archie is leading a knowledge translation project using video games as a tool for youth to learn about early psychosis intervention. WOULD YOU BE ABLE TO SHARE MORE ABOUT YOUR BACKGROUND AND WORK?

I’m a psychiatrist and I have been doing early intervention in psychosis for about 25 years. Over the years, I noticed that there were a lot of patients who were using cannabis at a very young age, so I became interested in [the] link between [cannabis] use and later development of psychosis. [...] If there was a link, we could help young people understand that, especially since many of them may actually not have a serious addiction, because they haven’t been using it for very long. And if they can understand that, they can get better faster. [...] So I [focused my research on] different knowledge translation strategies for [helping youth understand] the link [between psychosis and cannabis use]. [...] I am also a member of the Peterborough Centre for Addictions Research, [as well as] the Brain and Behavior subunit planner for the Undergraduate Medical Education [Program]. Education and teaching is something that I’m very interested in.

LET’S TALK SPECIFICALLY ABOUT YOUR RESEARCH ON CANNABIS USAGE AND RISK OF PSYCHOSIS. WHAT’S THE RELATIONSHIP BETWEEN THE TWO? WHAT ARE SOME RISK FACTORS FOR DEVELOPING PSYCHOSIS AMONG CANNABIS USERS?

The relationship is actually complex and multidirectional. I should note that there are a few main risk factors for developing psychosis through cannabis use. First is the concentration of tetrahydrocannabinol (THC) in marijuana. In Canada, marijuana THC content has drastically changed over the years. In the ‘70s and ‘80s, THC, which is the active ingredient in marijuana that’s related to psychosis and addiction, was about 2% for weed. But today in Canada, given the climate that we have here, the THC content has been genetically engineered so that it’s 15% to 30% in order to get a good yield of the crop. In contrast, the cannabidiol (CBD) content, which has medicinal properties but also has antipsychotic and anti-anxiety properties, has remained low at 2%. So, the balance between THC and CBD is off compared to what it was like for centuries, when it was around 2% THC and 2% CBD. Hashish traditionally had 5% THC, and that was considered high in the ‘60s and ‘70s. But of course that’s low today. So in conclusion, THC concentration is an important risk factor, since the higher the THC content, the more likely you are to find it appealing and use it more, which contributes to psychosis risk, especially for young people.

Secondly, there is an increased risk of cannabis use among people who have a genetic vulnerability for schizophrenia and serious mental illness. People who have a vulnerability for schizophrenia may have more cannabinoid type 1 (CB1) receptors in their brains, even before they develop psychosis or use marijuana. [...] People who have that genetic vulnerability use marijuana regularly. Not only do they have an increased risk of developing psychosis, they also have an increased risk of using more frequently. There are studies that show that as the risk for schizophrenia increases, there is an increased risk of using it regularly and more frequently. [...]

Thirdly, there’s also the initial age of use. As people use it younger and younger, the risks of developing substance use issues and psychosis issues increase dramatically. The age of regular use has changed over the last 30 years. In the ‘70s and ‘60s the age of regular use was university years — people would use three times a week or more when they were in their early 20s. But when my daughter was born, in the ‘90s and early ‘00s, the age of regular use dropped to high school years. So, people might have been 16 or 17 years of age when they were using three times a week or more. Now, in the last 10 years or so, the age of regular use has dropped even further to about grade 7 or grade 9. We’re talking 13 to 15 years of age. This is concerning, since the brain has a lot of developmental differences between a 14-year-old and a 21-year-old. Of course, lots of people use marijuana and have no problems with it. The vast majority of people use marijuana without a lot of risk, but there are populations that are vulnerable. Most of us are not aware of the fact that there may be serious mental illnesses, such as schizophrenia, bipolar illness, or addiction in their families [...].

WHAT ARE SOME SYMPTOMS OF PSYCHOSIS? HOW CAN SOMEONE REALIZE THAT THEY HAVE GONE THROUGH A PSYCHOTIC EPISODE?

Psychosis usually involves three main symptoms. First is a disturbance in perception. [For example], a person will hear sound as though it’s coming from the outside world, but actually it’s coming from a chemical imbalance in their brain, so they may hear it just like you’re hearing my voice now. It can be very difficult for someone experiencing psychosis to actually recognize that the experience is coming from a disorder in their brain as opposed to it really happening. Other people won’t hear what they are hearing so that is one of the ways that people figure out that they’re experiencing things different[ly]. [Secondly], people will come to different kinds of conclusions [or have delusions] because of their perceiving reality differently. So, if a person is seeing shadows, or seeing people and they think that they’re following them, then they’re going to believe that [...] somebody is trying to kill them or harm them. If you understand the perception that a person with psychosis is experiencing, then their belief systems actually do make sense because their beliefs are based on what they’re experiencing. The reason why it seems so odd is because in the regular reality, other people aren’t perceiving things the way they are, but once you kind of understand how they’re perceiving things, then their reality starts to make sense, because often it’s based on a disturbance of perception. [Finally], the other component is thought disorganization and behavior disorganization. The parts of the brain are not processing information properly. The person’s having disordered perceptions, all of that contributes to thought disorganization, and that also can lead to changes in their speech and changes in their behaviors.

WHAT IS CBD AND THC AND WHAT ARE THE DIFFERENCES IN THEIR EFFECTS? HOW DO THEIR CONCENTRATIONS CONTRIBUTE TO PSYCHOSIS AND ADDICTION?

[...] We know that THC has a dose-dependent effect on mental health symptoms. At low levels, THC can induce relaxation and a sense of calm. At higher levels, it starts to impair concentration and memory —particularly [...] emotionally difficult [and] painful memories— and it can induce a sense of euphoria. Then, at very high [...] intoxication levels, people can develop symptoms consistent with psychosis, such as paranoia. So they become suspicious, they misinterpret reality, they can have perceptual changes [in that] they can hear or see things differently, and their thoughts can become disorganized. [The] medical term

[for this is] cannabis-induced psychosis, which can occur up to a month after using marijuana. [However], people can also simply have cannabis intoxication, like other substances of abuse. [In general], if you consume too much, you can induce psychosis [via] alcohol, cocaine, and other substances of abuse as well. CBD, on the other hand, does not have any addictive properties [...]. But, CBD is being studied for being used for post-traumatic stress disorder (PTSD). So there is some evidence that it may be helpful for PTSD and, certainly, I think the US veterans have been using that. CBD has [also] been associated with a number of medicinal purposes, as well. It’s known to be effective for epilepsy, for example, in children who have severe epilepsy. It [and THC are] also helpful for chronic pain as well.

YOU CREATED A GAME RELATING TO EARLY PSYCHOSIS INTERVENTION, THE BACK TO REALITY SERIES. COULD YOU EXPLAIN WHAT THE GAME IS AND WHAT THE INSPIRATION WAS BEHIND IT?

We created the Back to Reality Series to specifically focus on marijuana and psychosis because we wanted to translate knowledge of the research previously mentioned to youth. I have also done some research on pathways to care for a first episode of psychosis. In this research, we were able to show that Black youth were more likely than other ethnic groups to experience police involvement in their pathways to care for the first episode of psychosis, and were less likely to be involved with family doctors. We thought that it would be important to not just educate youth about the risks, but also educate them about how to seek care in addition to mental health and addictions services. That way, you don’t end up having police involvement in order to get the kind of addiction and mental health care that you need [...].

We felt we needed something that the target audience would be able to use. A study in 2015 showed that 32% of youth who have had an episode of psychosis play video games on a daily basis, [with] 100% of them [having] access to a laptop or computer; 92% play video games on their cell phone and 83% had [a] console. Video games were a good way of reaching youth where they were at. Also, the nice thing about video games is that they can simulate visual and auditory experiences in a format that people can perceive, which helps more effectively communicate what psychosis symptoms can be like. A lot of people don’t understand what it means to have a psychotic episode. They may think that people are imagining it, or that they’re making it up.

The game is helpful because it teaches people mental health literacy, so they have a better understanding when doctors use words like “hallucinations” or “depression.” Another great thing noted was that people could see, hear, [and] read about mental health and addictions services in a format that was user-friendly and didn’t involve reading pamphlets. It’s great because you get to know what the services are like a little bit before you actually utilize them [...]. [...] I have a partnership with the Free For All Foundation, which is a charitable organization that works with Black families in the Bradenton area. We’re going to be recruiting about ten to twelve high school students associated with this organization and they are going to be participating in some tutorials. We’ll be using the Back To Reality Series like a homework assignment in order to provide a springboard into discussions about marijuana and psychosis. We’re going to do before-and-after testing to see if we can learn something about educating youth, not just using the video games, but also through the experience of having this discussion in a tutorial led by other young people.

[...] The other is a study for young people going through their first episode of psychosis, [where] they will be involved in individual interviews [...] to talk about what their understanding is between cannabis and psychosis. [...] We’re going to get a sense of what their beliefs are about this area. After having them play the game in another session, we’ll see whether it shapes or influences their thoughts, feelings, and beliefs about the relationship and whether they feel that they have learned anything from using the video games [...].