Interneuron Issue 5.2 by theinterneuron

Interneuron Volume 5. Issue 2. December 2017 Neuropsychiatry

Table of Contents

Editors Note & Editorial Board

Beat the Winter Blues! Ariana Tang

Artificial Intelligence: The “Human Doctor” at our Fingertips Carol Chen

The Evolution of Psychiatric Disorders Bailey McMaster

Dr. Anne Bassett: Exploring the Genetics of Schizophrenia Gaya Retna

Artificial Intelligence to Diagnose Psychiatric Disorders Denitsa Vasileva

Childhood Trauma and the Onset of Bipolar Disorder: A Paper Review Ayesha Sanjana

The Neuroscience Behind Addiction Sua Cho

It’s a Flourishing Life! Sawayra Owais

Treatment in Psychiatry - Art Therapy Shreyashi Saha

Towards the Establishment of Deep Brain Stimulation for Neuropsychiatric Disorders Marietou Daou

Biomarkers in Neuropsychiatry Tanya Khimani

An Interview with Dr. Freda Miller Lucy Lu

NAUS Neuroscience Everywhere Conference Review Amar Dholakia

SSSCR Presents: Stem Cells - Extending the Frontiers of Knowledge Avani Krishnan 3

INTERNEURON

EDITORâ&#x20AC;&#x2122;S NOTE Over the past decades, tremendous findings in the field of neuroscience have furthered our understanding of psychiatric conditions. Historically, Hippocrates was one of the first pioneers to suggest that psychological disorders have physiological roots. Later, the study of psychiatric disorders became mainly restricted to the context of mental illness, with more focus on psychoanalytic concepts, and less emphasis on their biological origins. Today, with better tools in hand, researchers are able to explore the diagnosis of psychological and mental conditions with molecular and genetic precision. Synchronizing the work conducted in different branches of neuroscience has allowed for the development of a more comprehensive knowledge of the brain. Additionally, with advanced computer programming, artificial intelligence, and neuroimaging tools, brain circuits are even more accurately understood. Nonetheless, the field of psychiatry is still far from complete. Despite the potential benefits of genetic modification and manipulation of neural activity in pre-clinical studies, the majority of the clinical community is still battling their conditions with conventional therapies, while the translation of the new techniques to humans has faced many drawbacks. Given the importance of new research in neuropsychiatry, we decided to dedicate our second issue of the year to this critical topic. We should thank all our talented writers and artists which made this issue an incredible phenomenon. Here we proudly invite you to read many great articles ranging from the application of artificial intelligence to the identification of novel psychotherapeutic approaches. Additionally, the issue features an interview with Dr. Freda Miller, senior scientist at the University of Toronto, who along with David Kaplan and their trainees, has identified a potential drug for neurodegenerative diseases. You can also read about the review of the Neuroscience Association Conference, made possible by the hard work of the NAUS executive board. With all that said, the Interneuron team wishes everyone a Merry Christmas and an incredible new year, and we hope you enjoy reading the second issue during your holidays!

Parandis and Waleed

CO-EDITORS-IN-CHIEF Acknowledgements

Cover illustration source: Vocativ Illustrator: Jack Dylan

CONTRIBUTORS

Volume 5. Issue 2. December 2017

Editorial

Board 2017 2018

Parandis Kazemi

Waleed Khan

Andrea Macanovic

Wazaira Khan

Clara Hong

Belinda Hoang

Kayla Liu

Amar Dholakia

Editor-in-Chief

Submissions Editor

Layout Design

Submissions Editor

Layout Design

Editor-in-Chief

Webmaster

Marketing Director

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Beat the Winter Blues! Beat the Winter Blues! By Ariana Tang

The winter: when getting to morning classes seem much harder than it should be, and the idea of staying under a blanket becomes much more appealing. The long nights and dreary cold of the winter often leave people feeling “blue”, gloomy, unmotivated, and counting down the days until summer. However, this mild gloominess can become severe and distressing – in which case, it becomes known as seasonal affective disorder (SAD). Approximately 2% of Canadians are affected by SAD1. Seasonal affective disorder is classified under major depressive disorder (MDD), as well as bipolar I and II disorder2. It is diagnosed when a patient presents with symptoms of these illnesses with a seasonal pattern, i.e. the recurrence of a major depressive episode or the change from major depression to mania/hypomania during a specific time of the year2. It is important to note SAD is simply more than just feeling “blue” during the winter, and should only be diagnosed by a healthcare professional. A milder form of SAD is known as subsyndromal SAD (s-SAD) or more colloquially, the “winter blues”, diagnosed if symptoms do not quite meet the criteria for SAD². One explanation for seasonal psychological disturbance is an altered circaReferences

dian rhythm response to seasonal changes; this can be seen in melatonin levels3. Melatonin is a hormone secreted by the pineal gland in the brain that regulates sleep and wakefulness, and its secretion is the highest in the night. Wehr and colleagues found that melatonin secretion was longer in the winter than in the summer for those affected with SAD, while healthy participants showed no change in melatonin secretion between the summer and winter³. This suggests that SAD-affected individuals have an increased sensitivity to seasonal changes. Individuals affected with SAD have also been shown to have higher levels of SERT (serotonin transporter), decreasing the availability of serotonin in the synapse and leading to lower serotonin activity⁴. Serotonin helps regulate mood and is often found in lower levels in the brains of depressed individuals. Furthermore, there seems to be a genetic predisposition to SAD⁵. Thankfully, not all hope is lost. There are a number of tools which can ease the “winter blues” and perhaps make your days a little brighter. (Disclaimer: please note that none of these should be considered “cures” for SAD or substitutes for a healthcare professional’s advice.)

1. Melrose S. Seasonal Affective Disorder: An Overview of Assessment and Treatment Approaches. Depress Res Treat [Internet]. 2015 [cited 2017 Nov 9];2015. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673349/ 2. Kurlansik SL, Ibay AD. Seasonal affective disorder. Am Fam Physician. 2012 Dec 1;86(11):1037–41. 3. Wehr TA, Duncan WC, Sher L, Aeschbach D, Schwartz PJ, Turner EH, et al. A Circadian Signal of Change of Season in Patients With Seasonal Affective Disorder. Archives of General Psychiatry. 2001 Dec 1;58(12):1108. 4. Mc Mahon B, Andersen SB, Madsen MK, Hjordt LV, Hageman I, Dam H, et al. Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder. Brain. 2016 May;139(Pt 5):1605–14.

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1. Light therapy

This can be used for both SAD and subsyndromal s-SAD. Light therapy involves sitting in front of a bright light for a set period of time each day in the winter, usually in the morning¹. It has been widely studied, and the current consensus is that it is highly effective for the majority of people living with SAD13. (Light therapy lamps are available at Robarts! More information at this link: https://onesearch.library.utoronto.ca/need-little-sunshine-light-therapy-lamps-now-available-robarts-library)

2. Vitamin D supplements Artwork by Baotian Fu

3. Increase carbohydrate intake Yes – carbohydrates are not evil! Anecdotally, many people turn to carbohydrate-rich foods (i.e. “comfort foods” like cake, pizza, pie) when they are feeling down because it makes them feel better. Similarly, in the winter, those affected with SAD tend to crave more carbohydrates10. Carbohydrate ingestion increases blood tryptophan levels, and tryptophan is a precursor to serotonin11. Thus, an increased carbohydrate intake leads to increased serotonin, which leads to a better mood. However, this is not a free pass to go to town on potato chips and muffins! Make sure your carbohydrate intake also contains a good amount of fibre, and is also paired with protein and fat – this will lower the glycemic index of your food so you don’t experience the dreaded “sugar crash”12.

People affected with SAD and depression tend to have lower vitamin D levels6,7. Short wave sunlight, which the body requires in order to synthesize vitamin D is not as widely available during the winter8. As such, these findings are unsurprising. Several studies have shown that high doses of vitamin D can improve SAD symptoms with a caveat: only those who showed a significant increase in serum vitamin D had their symptoms alleviated7,9. Therefore, the literature suggests that taking a high dose of vitamin D may be beneficial for symptoms.

4. Get professional help There is no shame in seeking professional help for SAD, and it probably is the best option if your symptoms are overwhelming and greatly affecting your life. Some mental health resources right at U of T (which can be helpful if you do not have a family doctor nearby) can be found here: https://www.studentlife. utoronto.ca/hwc/feeling#node-3276.

References cont’d 5. Targum SD, Rosenthal N. Seasonal Affective Disorder. Psychiatry (Edgmont). 2008 May;5(5):31–3. 6. Anglin RES, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100–7. 7. Gloth FM, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. J Nutr Health Aging. 1999;3(1):5–7. 8. Stumpf WE, Privette TH, Privette TH. Light, vitamin D and psychiatry. Psychopharmacology. 1989 Mar 1;97(3):285–94. 9. Shipowick CD, Moore CB, Corbett C, Bindler R. Vitamin D and depressive symptoms in women during the winter: A pilot study. Applied Nursing Research. 2009;22(3):221–5. 10. Rosenthal NE, Genhart MJ, Caballero B, Jacobsen FM, Skwerer RG, Coursey RD, et al. Psychobiological effects of carbohydrate- and protein-rich meals in patients with seasonal affective disorder and normal controls. Biological Psychiatry. 1989 Apr 15;25(8):1029–40. 11. Wurtman, Richard K. Effects of Nutrients on Neurotransmitter Release [Internet]. National Academies Press (US); 1994 [cited 2017 Nov 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK209058/ 12. Cui H, Yang Y, Bian L, He M. [Effect of food composition of mixed food on glycemic index]. Wei Sheng Yan Jiu. 1999 Nov;28(6):356–8. 13. Pail G, Huf W, Pjrek E, Winkler D, Willeit M, Praschak-Rieder N, et al. Bright-light therapy in the treatment of mood disorders. Neuropsychobiology. 2011;64(3):152–62.

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Artificial Intelligence: The “Human Doctor” at our Fingertips Carol Chen With 1 in 5 adults in America experiencing mental illness problems today1, we need more advanced technologies than ever to quickly and accurately diagnose mental illnesses. For most people, the timeline for the diagnosis and treatment of mental illnesses is much too long. Luckily, scientists and engineers are developing artificial intelligence tools to treat patients early in the stages of mental decline. Jim Schwoebel, engineer and CEO of NeuroLex Diagnostics, is currently working on a tool for doctors to quickly screen patients for schizophrenia. Schizophrenia is a mental illness where a person is unable to distinguish between fantasy and reality. Since a major symptom of schizophrenia is poor and dysfunctional communication, this “schizophrenic screener” will take the speech transcript of a recording taken from a patient during an appointment and analyze specific speech patterns and verbal cues. The screener will then indicate, most likely by a number, the patient’s probability of developing schizophrenia.2 Once he can develop a tool that can accurately diagnose mental illnesses, Schwoebel’s next step is to add another function that can recommend specific medications for these patients. He plans to do a pre-post study to analyze the speech patterns

of patients after being given a specific medication during their stay at the hospital. If the patient shows fewer symptoms after being given a specific medication, the tool will recommend that medication to other patients with similar speech patterns.2 In this way, medications can be prescribed to patients without the consultation of a health practitioner. Studies have shown that suicide also has a strong correlation to mental illness.3 To this day, much research has been done in investigating how artificial intelligence could prevent people from committing suicide. In April, Colin Walsh, a professional data scientist at Vanderbilt University Medical Centre, published the first steps of his research in an algorithm that is 90% accurate to predict the likelihood of a person committing suicide. Walsh and his team created the algorithm based on the analyzed data of over 5000 patients admitted in the hospital. Their next steps, which Walsh hopes to accomplish within the next two years, include testing the algorithm on data from other hospitals, as well as to find a possible intervention early in the diagnosis.4 Since social media is a massively popular communication method, scientists have integrated artificial intelligence into the social realm to prevent

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the suicidal rate. Facebook recently tested an algorithm that scans posts and status updates to mark people at risk of committing self-harm. Although there is a delicate balance between safety and privacy, this algorithm may warn family members and close friends before suicidal attempts occur.5 There are, inevitably, many controversies on artificial intelligence as diagnosis tools. Machines and tools can perform minor errors at times, and an incorrect input can be catastrophic for the patient. Patients also display a continuum of symptoms, and algorithms tend to focus on the exact boundary between being diagnosed or not. In addition, people of different cultures, races and background display different

symptoms and ways of speech that may be analyzed incorrectly by the machine. Future research needs to be investigated on creating tools that can analyze a broad spectrum of symptoms and specific cases.2 Due to the rapidly increasing rate of the number of people being diagnosed with mental disorders, using artificial intelligence tools may be the quickest and most reliable option. Artificial intelligence can also give a more objective and quantitative assessment than human doctors and radiology machines.2 In this technology booming world, artificial intelligence may be the new â&#x20AC;&#x153;doctorâ&#x20AC;? we consult in the future generation.

References

1. NAMI. (n.d.) Retrieved November 17, 2017, from https://www.nami.org/Learn-More/Mental-Health-By-the-Numbers 2. Frankel, J. (2016, August 23). How Artificial Selection Could Help Diagnose Mental Disorders. Retrieved November 17, 2017, from https:// www.theatlantic.com/health/archive/2016/08/could-artificial-intelligence-improve-psychiatry/496964/ 3. The Relationship Between Suicide and Mental Health. (2016, May 25). Retrieved November 17, 2017, from https://suicideprevention.ca/ the-relationship-between-suicide-and-mental-health/ 4. Goldhill, O. (2017, June 10). Artificial intelligence can now predict suicide risk with remarkable accuracy. Retrieved November 17, 2017, from https://qz.com/1001968/artificial-intelligence-can-now-predict-suicide-with-remarkable-accuracy/ 5. Stark, H. (2017, October 30). Artificial Intelligence Is Here and it Wants to Revolutionize Psychiatry. Retrieved November 17, 2017, from https://www.forbes.com/sites/haroldstark/2017/10/30/artificial-intelligence-is-here-and-it-wants-to-revolutionize-psychiatry/#c34ecff69034

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By Bailey McMaster

The Evolution of Psychiatric Disorders

Despite the debilitating impact of psychiatric illnesses, evolution has yet to rid humans of these diseases. As many psychiatric illnesses are known to have a genetic component, studying the evolutionary history of humans, these illnesses, and related functions can provide new insight as to how they arose. Specifically, scientists have made great progress in understanding schizophrenia through an evolutionary perspective. It has been found that schizophrenia leads to lower fecundity – the number of children the individual has – in affected people1. According to Darwin’s theory of evolution, this should lead to a decrease in the presence of schizophrenia in the population. However, this does not occur, as schizophrenia rates in populations have remained steady, and are constant across most populations2. There are various explanations that have emerged in an attempt to explain how schizophrenia could have evolved in the human genome. These theories fall into two categories: those which state schizophrenia is advantageous, and those which state that having schizophrenia is disadvantageous. Theories that claim schizophrenia could have been developed as an advantageous trait fall under three types of selection: individual, kin, or group. One group theory claims that tribes of the past proliferated and split to maintain specific numbers in the tribe. In these scenarios, a person with schizotypal traits, who could use paranoia, delusions, and religion to draw members towards themselves, would be effective as a leader of an offshoot group, inciting a new culture3. Prominent theories of schizophrenia as a disadvantageous by-product of evolution focus on the evolutionary development of the human brain. Common symptoms of schizophrenia involve speech-related processes, such as auditory hallucinations and jumbling speech. It has been proposed that the genes associated with speech development throughout human history are closely connected to the genes that are now associated with schizophrenia, such as FOXP2. Schizophrenia may have been a minor inconvenient development, from an evolutionary perspective, accompanying the immensely beneficial production of speech4. In evolution, there is indeed a fine line between deleterious and beneficial mutations, and trying to understand psychiatric illnesses through the lens of genetics and evolutionary history is still relatively new and developing. Scientists hope that with the ongoing advancements with the human genome, novel developments can occur by analyzing the genetic basis to psychiatric illnesses such as schizophrenia. In addition to schizophrenia, scientists are looking into doing similar research and analysis for other mental illnesses as well, such as depression, obsessive compulsive disorder, anorexia, and substance abuse disorder2. This could lead to a better understanding of the illnesses as a whole, and relevant treatments to these illnesses.

References

1Polimeni, J. & Reiss, J. P. Evolutionary Perspectives on Schizophrenia. The Canadian Journal of Psychiatry 48, 34–39 (2003). 2Schultz, D. Mental Disorders And Evolution: What Would Darwin Say About Schizophrenia? NPR (2012). Available at: https://www.npr.org/sections/ health-shots/2012/11/16/165149933/mental-disorders-and-evolution-what-would-darwin-say-about-schizophrenia. (Accessed: 12th November 2017) 3Polimeni, J. & Reiss, J. P. Evolutionary Perspectives on Schizophrenia. The Canadian Journal of Psychiatry 48, 34–39 (2003). ⁴Reardon, S. Geneticists are starting to unravel evolutions role in mental illness. Nature 551, 15–16 (2017).

By Gaya Retna

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Dr. Anne Bassett:

Exploring the Genetics of Schizophrenia

Schizophrenia is a chronic mental disability in which an individual feels as though they have lost touch with reality â&#x20AC;&#x201C; characterized by depersonalization, hallucinations, emotional and behavioural disruption as well as poor executive functioning. It is a psychiatric condition which can be incredibly debilitating, and it affects 1 in 100 people(3). The origins and mechanisms responsible for the illness have remained undiscovered for a long time. However, a major breakthrough involving the identification of genetic risk factors has come to light with progressing research by Canadian neuroscientist Dr. Anne Bassett. Patient management has potential for improvement with her clinical findings and work. Dr. Anne Bassett is the Director of the Clincial Genetics Research Program in the Clinical Research Department and Clincial Scientist in the Campbell Family Mental Health Research Insitute at CAMH(2). She also holds the Dalglish Chair at UHN(1,2), and is a Senior Scientist at the Toronto General Research Institute(2). Asides from research, she is a Professor of Psychiatry at the University of Toronto, and teaches at the Schizophrenia Society of Canada as part of her public service(2). Her work has a centralization of clinical practice, as a significant area of her research involves interpreting genetic findings into medical use(3). As the principal investigator of studies towards the genetic structure and subtypes of schizophrenia(2), Dr. Anne Bassett 's impressive contribution to neurobiological research has earned her worldwide recognition(4). Her team's research strives to lead the way in finding the various genetic elements of complex developmental disorders, through the examination of genomic disorders and variants associated with schizophrenia and diseases(1), which have the potential to reveal mechanisms and factors required in the relevant gene expressions. She has renowned expertise in adults with 22q11.2 deletion syndrome (22q11.2DS), which is a common yet overlooked genetic condition(3). The missing genetic piece, which is the 22q11.2 deletion, identified with 22q11.2DS serves as the first discovered molecular genetic risk factor contributing to schizophrenia(3). There is a 1 in 4 chance that schizophrenia will manifest itself in individuals born with a 22q11.2 deletion(2). 1 out of every 100 schizophrenic patients have the chance of finding the 22q11.2 through a standard clinical blood test(2). Along with this significant genetic mutation, other unique genetic structural variants are components that support the development of schizophrenia(4). These resources play a major role in the awareness of developmental and degenerative advancements in schizophrenic pathogenesis, as well as other complex conditions(3). It is undoubted that this research will create pathways for improved understanding of the biological mechanisms behind developmental disorders including, but not limited to, schizophrenia(1). With Dr. Anne Bassett's team utilising the latest genetic assessments and technologies in the study of adults suffering from this complex multisystem condition, specialized diagnoses and delineation of disease networks are to be discovered(1). This will lead to the development of prevention and management strategies of many debilitating lifelong conditions such as 22q11.2 deletion syndrome for schizophrenia. References 1. Anne Bassett [Internet]. Anne Bassett | UHN Research. University Health Network. Available from: https://www.uhnresearch.ca/researcher/anne-bassett 2. Dr. Anne Bassett [Internet]. Scientific Staff Profiles. Centre for Addiction and Mental Health; 2012. Available from: http://www.camh.ca/en/research/about_research_at_ CAMH/scientific_staff_profile/Pages/Anne-Bassett.aspx 3. Government of Canada, Industry Canada, Canada Research Chairs. Canada Research Chairs [Internet]. Government of Canada, Industry Canada, Canada Research Chairs. 2012. Available from: http://www.chairs-chaires.gc.ca/chairholders-titulaires/profile-eng.aspx?profileID=614 4. Dr. Anne S. Bassett [Internet]. Department of Psychiatry. University of Toronto; 2017. Available from: http://www.psychiatry.utoronto.ca/people/dr-anne-s-bassett/

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Artificial Intelligence to Diagnose Psychiatric Disorders By Denitsa Vasileva

â&#x20AC;&#x153;Artificial intelligenceâ&#x20AC;? is in many ways the defining buzz word of the second decade of the 20th century. You have likely encountered it multiple times in new reports, newspaper articles, or talks given by professors at university. Artificial intelligence has the potential to alter our modern day lives and have the same impact on the 21st century that the invention of the internet and the personalized computer did on the 20th century. But what is arti12

ficial intelligence? The notion of artificial intelligence is most often associated with doom-and-gloom apocalyptic blockbusters (that somehow continue to be produced despite being devoid of any redeeming qualities) in which massive robots outwit and overpower humanity. However, in reality, far from being an agent of destruction. Despite the objections of some prominent tech leaders such as Eon Musk and Bill Gates, artificial intelligence can prove to

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be a powerful tool in advancing disciplines such as psychiatry and medicine. Initially, the link between artificial intelligence and psychiatry may seem rather tenuous. After all, how can robots help diagnose illness or prevent suicide? In fact, artificial intelligence is more than just robots. It refers to the creation of systems that can undertake tasks that usually require human intelligence. Artificial intelligence has found a surprising application in psychiatry where it can be used to predict how likely an individual is to attempt to commit suicide. This research is still in its early stages but it has great potential to allow doctors to detect and prevent patients from taking their lives. Moreover, Facebook has recently joined the effort to use Artificial Intelligence as a method of suicide prevention by scouring through the pages of thousands of its users, identifying which individuals have expressed an intent to commit suicide and notifying their friends and families. Artificial Intelligence can also be ap-

plied in other domains of psychiatry and neuroscience. For example, researchers are currently examining the utility of artificial intelligence in diagnosing patients with ADHD. Finally, and perhaps most crucially, the use of artificial intelligence in psychiatry can eliminate the stigma that still accompanies individuals seeking treatment for mental health issues and is one of the primary hurdles barricading access to care. By using relying on machines, rather than conversations with humans, artificial intelligence has the potential to remove this barrier and connect thousands of people to much needed care. However, as with any technological innovation, artificial intelligence - particularly as implemented in a healthcare setting - is somewhat of a double-edge sword as it can raise questions of whether technology is stifling human interaction and detrimental to our ability to form interpersonal relationships. After all, AI might all but eradicate the doctor-patient relationship whose importance has long been held in high regard. Movies and popular culture have thought us that robots will one day take over the world and decimate mankind. However, in reality, they are part of a fast-paced revolution going on in pretty much every field of medicine, including psychiatry, and has the power to liberate us from some of our own worst fears and save countless lives.

References Stark H. Artificial Intelligence Is Here And It Wants To Revolutionize Psychiatry [Internet]. Forbes. Forbes Magazine; 2017 [cited 2017Nov17]. Available from: https://www.forbes.com/sites/haroldstark/2017/10/30/artificial-intelligence-is-here-and-it-wants-to-revolutionize-psychiatry/#55ad22dc6903

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Childhood Trauma and the Onset of Bipolar Disorder

A PAPER REVIEW

Ayesha Sanjana Imagine you are on a trip with your friends and having fun. You are really excited and happy but then suddenly your mood changes. You feel depressed about anything and without any reason. How would you feel when you notice that you don’t have any control over your mood? This psychological disorder is known as “Bipolar Disorder” (BD) which affects 1 out of every 100 people in the world (1). Scientists have found that when someone suffers from childhood trauma, such as emotional, physical or sexual, they develop a greater susceptibility to develop bipolar disorder, especially severe bipolar disorder (2). But why should we care about bipolar disorder? The answer is in the statistics. According to the National Institute of Mental Health, around 5.7 million people in the US have BD, that is, 2 out of every 100 people (1). Approximately 82.9% of individuals who 14

are suffering from bipolar disorder suffer from the severe form (1). Canada has nearly 390,094 people who are suffering from this disorder (1). Additionally, around 12-15 million people in India live with BD (1). Such a disorder that is affecting around 2 in every 100 people in the US and nearly 15 million people in India deserves more careful attention (1). Childhood trauma and bipolar disorder are said to be strongly correlated (2). Childhood trauma is a negative experience that a child goes through in the form of verbal, physical and sexual neglect or abuse (2). These kinds of traumas can establish a lifetime risk of BD (2). BD does not only encompass emotional dysregulation but additional cognitive deficits (decrease in cognitive activities such as working memory and attention), drug misuse, and even occasional attempts in suicide (2). Furthermore, it also can alter biolog-

Volume 5. Issue 2. December 2017 ical pathways and underlying genetic makeup (2). It has been said that there is a higher prevalence for individuals suffering from emotional abuse and neglect than physical abuse (1) and according to research in psychological and molecular science, these experiences establish frequent mood swings (2). Research has shown that BD can increase activation of the amygdala, a region in the brain involved in the regulation of emotion and fear (2). Emotional abuse and neglect are so traumatic that they are considered a specific risk factor for type 1 BD (2). When bipolar disorder happens because of emotional abuse it is called type 1 BD (2). People with BD who have gone through physical and sexual abuse exhibit higher impulsivity and lower brain inhibitory control or response inhibition (process that inhibit inappropriate addiction to certain stimuli) (2). In addition, physical abuse has shown to affect the hypothalamic-pituitary-adrenal (HPA) axis by increasing its activity. Scientists have discovered that cannabis reduce hyper activity in HPA axis therefore, some people are prone to cannabis misuse (2). As such, researchers have proposed a two-hit model on the association of physical abuse and cannabis misuse (2). According to the two-hit model, prenatal or postnatal (before and after birth) exposure to stress can change the genetic makeup in brain, for example increased activity in HPA, by making people vulnerable (2).Furthermore, between the ages of 18 to 39, when an individual is subject to more stress and potential substance abuse, it can establish disorder in the individual (2). The effects of BD on neuroplasticity, inflammation and circadian rhythms as well as the underlying molecular changes of BD are among the most researched areas of bipolar disorder (2). Brain-derived neurotrophic factor (BDNF) levels, an essen-

tial neurotrophic factor that maintains the growth and differentiation of neurons through kinesis, are lowered in those with BD (2). More specifically, individuals exposed to sexual abuse at an early age have been shown to carry the Val66Met polymorphism in the BDNF gene (2). Val66Met substitutes Met for Val in the 66 position of the BDNF gene, where VAL and MET are important amino acids that serve as the building blocks of protein (2). Furthermore, BD alters the inflammatory pathway by encoding protein TLR2, a receptor essential in the immune-inflammatory response (2). People with BD often have insomnia as their circadian genes are encoded differently (2). Polymorphisms in circadian genes or Circadian Locomotor Output Cycles Kaput (CLOCK) genes has been associated to higher risk of suicide attempts and depression (2). All of these mentions some of the highlights from current researches in BD. With focus on the early stages of the disorder, there is more room for preventative action in terms of early diagnosis and symptom improvement, aiming for higher quality of life for those living with BD and ultimately finding a cure (2). However, debates are ongoing regarding the prevention of BD (2). Researchers have been using different kinds of psychological technique which can control humanâ&#x20AC;&#x2122;s emotion to treat BD (2). However, many treatments are based on psychological technique rather than physiological technique (2). Furthermore, there are still many questions that remain unanswered (2). For example, what are the specific genetic changes that occur in the HPA axis? (2) Although there is still much left to discover, we must work to spread awareness of the importance and severity of BD.

References

1. Bipolar Lives. Bipolar disorder statistics [Internet]. Bipolar Lives. Available from: http://www.bipolar-lives.com/bipolar-disorder-statistics. html [Accessed 15th November 2017] 2. Aas M, Henry C, Andreassen OA, Bellivier F, Melle I, Etain B. The role of childhood trauma in bipolar disorders. International Journal of Bipolar Disorders. 2016;4(1).

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The Neuroscience Behind Addiction

Sua Cho

“Prioritizing Me” Artwork by: Baotian Fu

Volume 5. Issue 2. December 2017 Addiction is a condition that results in a person compulsively taking substances despite negative consequences (4). When a person first takes a drug or other substances, the brain perceives it as a reward (4). Continuous consumption of the substance leads to an alteration in the balance of the brain reward system (4), resulting in more positive brain activity in response to drug-related cues (3). Current research demonstrates that this condi tion is heavily linked to dopamine levels. Dopamine is a neurotransmitter involved in the brainâ&#x20AC;&#x2122;s reward system (4). It does not signal for reward but moderates the positive effects of receiving a reward such as sex or food and it also increases in anticipation of a rewarding behaviour (4). Addictive tendencies are thought to be genetic (1) as there are identifiable physical traits in people with a family history of substance abuse (2). These traits may include smaller volume of limbic brain regions, reduced white brain matter, as well as altered response to inhibitory control (2). Adolescents have an increased vulnerability in developing addiction, and these tendencies can be identified by analyzing their behavioural and physiological traits (2). For instance, people who perform poorer on tests of inhibition and working memory, and have smaller brain sizes in reward and cognitive control regions are predictive of possible substance abuse tendencies (2). These physiological traits can be further identified via neuroimaging techniques such as MRI, fMRI, and PET (3). MRI is often analyzed by using voxel-based morphometry to distinguish and estimate tissue and ventricular sizes by analyzing the contrast between the grey and white matter in high resolution MRI imaging (3). Research that used this technique found that drug abuse correlated with a reduction of frontal lobes, subcortical structures and prefrontal cortex, as well as a decline in grey matter in frontal regions (3). fMRI measures brain activity

by using blood oxygenation level dependent endogenous contrast (3). It is often implemented when performing experiments that engage specific cognitive processes by using specific stimuli (3). Both fMRI and MRI are significant in identifying the physical traits of addiction thereby identifying future biomarkers of addiction (3). In current research, PET also has been used to examine dopamine release in the striatum (4) and has found that blunted striatal dopa m i n e transmission resulted in greater impulsivity, while decreasing motivation, resulting in greater drug intake (4). Therefore, PET is also very significant in identifying biomarkers of addiction (4). Despite the extensive research regarding addiction, there is still much to learn about neurological addictive tendencies as we still lack specific understanding of the process or the factors that affect addiction. To further our understanding, we need to use updated neuroimaging techniques to get a better understanding of the differences between a control brain, a brain with addictive tendencies, and a brain already undergoing addiction. This could be done by combining fMRI and PET imaging systems as fMRI alone cannot be used to certainly infer that a certain neurological process is affected by certain disturbances; whereas combining fMRI and PET would allow us to be able to pinpoint the relationship between the two more accurately (3). This would result in a more accurate understanding of how specific brain processes are affected by addiction as well as make it easier in identifying specific biomarkers related to addiction (3). By using updated neuroimaging techniques, we would be able to identify more physiological biomarkers for addiction, which could be helpful in the development of preventative measures as well as better treatment options.

References

1. Dick, D. (2016). The Genetics of Addiction: Where Do We Go From Here? J Stud Alcohol Drugs, 77(5), 673-675. 2. Squeglia, L. M., & Cservenka, A. (2017). Adolescence and drug use vulnerability: findings from neuroimaging. Current Opinion in Behavioral Sciences, 13, 164-170. doi:10.1016/j.cobeha.2016.12.005 3. Suckling, J., & Nestor, L. J. (2016). The neurobiology of addiction: the perspective from magnetic resonance imaging present and future. Addiction, 112(2), 360-369. doi:10.1111/add.13474 4. Trifilieff, P., Ducrocq, F., Veldt, S. V., & Martinez, D. (2017). Blunted Dopamine Transmission in Addiction: Potential Mechanisms and Implications for Behavior. Seminars in Nuclear Medicine, 47(1), 64-74. doi:10.1053/j.semnuclmed.2016.09.003

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It’s a Flourishing Life!

Sawayra Owais

Post-traumatic stress disorder (PTSD) is an anxiety disorder characterized by recurrent, intrusive thoughts after experiencing, witnessing, or learning about a traumatic event. Prevalence rates are found to be 1 – 12%, with socially disadvantaged populations, younger individuals, and first responders having higher rates (1). Individuals with PTSD experience significant distress within their life, including negative expectations of the world, anhedonia (inability to take pleasure in things previously found pleasurable), and constricted positive affect. Recognizing that PTSD has a burden at the individual, family, and societal level, attention has

been paid to the biological correlates of PTSD. Recently, the study of the influence of intestinal bacteria, or the “gut microbiome”, on psychiatric disorders has flourished, with PTSD being no exception. Studies have shown that individuals with PTSD have higher levels of inflammatory markers like interleukin-6 or C-reactive protein and the microbiome is known to control levels of these inflammatory cytokines (2). This finding begs the question: Do individuals with PTSD have a different microbiome profile than their healthy counterparts? This question is what drove authors to conduct a study involving 18 individuals with PTSD and 12

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trauma exposed control participants and differences in colonic bacteria families (2). While they found no statistically significant differences between these two groups in the diversity of microbial communities, they found that the risk of developing PTSD was associated with lower population of three specific phyla (Actinobacteria, Lentisphaerae, Verrucomicrobia). However, the authors note that these differences may be due to psychiatric medication use. Given the potential dysbiosis in the microbiome of individuals with PTSD, research has turned to probiotics, or administration of ‘good’ bacteria, for treatment of PTSD. For instance, Reber et al. (2016) found that administration of Mycobacterium Vaccae decreased stress behaviours in a murine social stress paradigm. Specifically, these mice demonstrated decreased flight and submissive behaviours when in the presence of a dominant aggressor mouse (3). Importantly, the researchers found increased levels of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in serotonin biosynthesis, in mice treated with the bacteria in comparisons to the control group (3). Critically, high levels of serotonin are known to correlate with decreased stress and anxiety behaviours (4). Seeing success in animal studies, attention is now turning to clinical trials for the treatment

of PTSD with probiotics. For example, studies have found that administration of lactobacillus and bifidobacterium had a positive impact on mood, anxiety, and stress in healthy participants (5,4). These positive finding warrant larger, adequately powered randomized controlled trials with individuals with PTSD as participants to further elucidate the gut-brain interaction. Clinical trials investigating the effects of probiotics on individuals with PTSD are currently underway. However, more research is still needed to determine the frequency, timing, and amount of probiotic administration to ensure we can capitalize on what these bacteria have to offer. It’s a flourishing life, after all.

References

1. Post-Traumatic Stress Disorder — NEJM [Internet]. New England Journal of Medicine. [cited 2017 Nov 18]. Available from: http://www.nejm.org/doi/full/10.1056/NEJMra1612499 2. Hemmings SM j, Malan-müller S, Heuvel LL van den, Demmitt BA, Stanislawski MA, Smith DG, et al. The Microbiome in Posttraumatic Stress Disorder and Trauma-exposed Controls: An Exploratory Study. Psychosom Med. 2017 Oct 1;79(8):936–46. 3. Reber SO, Siebler PH, Donner NC, Morton JT, Smith DG, Kopelman JM, et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proc Natl Acad Sci. 2016 May 31;113(22):E3130–9. 4. Leclercq S, Forsythe P, Bienenstock J. Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key? Can J Psychiatry Rev Can Psychiatr. 2016 Apr;61(4):204–13. 5. Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, et al. Assessment of psychotropic-like properties of a probiotic formulation (<span class=“italic”>Lactobacillus helveticus</span> R0052 and <span class=“italic”>Bifidobacterium longum</ span> R0175) in rats and human subjects. Br J Nutr. 2011 Mar;105(5):755–64.

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Treatments in Psychiatry Art Therapy Shreyashi

Saha

â&#x20AC;&#x153;Tranquil Thoughtsâ&#x20AC;? Artwork by: Baotian Fu

Art therapy is the use of painting, drawing or sculpture to create a visual representation of thoughts, feelings and emotions. The rationale behind the first art therpy project in this 20

service was the belief that people with mental health problems needed to express themselves and often had difficulty doing so (1-3). Studies from all around the world has pro-

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vided evidence to identify art’s precise role in treatment. Art therapy has a long history in mental health care. In 2000, a review of ‘arts for health’ activity by the Health Development Agency in the UK suggested that arts participation might have health benefits such as increased self-esteem and self-determination. Some studies suggested specific benefits for mental health, including fewer hospital readmissions, lower levels of depression and reduced rates of general practitioner consultation (2). In a European study by Brady, Moss and Kelly, a mixed method design was adopted to evaluate the role of art therapy within the services provided for mental illnesses. There is growing evidence pointing that art projects have helped develop wide social networks, understand and deal better with mental health issues and gain confidence and self-esteem. Perhaps the simple action of creating something with one’s bare hands helps realign thoughts (4). Analysing the creation leads into the cognitive processing of the client. Myriad benefits were identified by both staff and users, including reducing social isolation, building confidence and providing a positive activity opportunity for self-expression (5). Clients benefited from the focus on their talents and the emphasis on restoring their pleasure and enjoyment. This form of therapy also provided a safe space for personal expression and a sense

of achievement. Research advocates that art increases the potential for communication for withdrawn and defensive psychiatric patients (2-5). Contrastingly, research has only been able to provide data from staff and clients who have benefited from art therapy. Hence, the conclusions maybe biased and lacking the consideration of multiple perspectives. The Achilles heel of art therapy is whether it makes a difference if art therapy is administered by a social worker, an artist or an art therapist (6). Would it be possible to help an individual find wellness without a great deal of professional intervention? The challenge to this endeavour is the widespread use of creativity in art therapy by individuals without formal art therapy education (7). For therapists, there may be a tendency to want to interpret their clients do in a given modality. Practitioners may be tempted to project their own conclusions about the content, hindering the whole idea of art therapy being a form of expression for defensive clients (6,7). Acceptance of art therapy has increased worldwide. Research indicates that growth in the defining training standard will further strengthen the practice. Through growing recognition by health systems and communities, art therapists can develop and implement recovery frameworks for a wider clientele. Hence, art therapy is securing a firmer place in the field of psychiatric treatment (2).

References

1. Womenscollegehospital.ca. (2017). Women’s College Hospital - Art Therapy. [online] Available at: http://www.womenscollegehospital.ca/ programs-and-services/sexual-assault-domestic-violence-care-centre/art-therapy [Accessed 30 Nov. 2017]. 2. Fenner, P., Abdelazim, R. S., Bräuninger, I., Strehlow, G., & Seifert, K. (2017). Provision of arts therapies for people with severe mental illness. Current Opinion in Psychiatry, 30(4), 306-311. doi:10.1097/yco.0000000000000338 3. Cummings, C. (2017). The science of therapeutic images. History of the Human Sciences, 30(2), 69-87. doi:10.1177/0952695116687226 4. Brady, C., Moss, H., & Kelly, B. D. (2016). A fuller picture: evaluating an art therapy programme in a multidisciplinary mental health service. Medical Humanities, 43(1), 30-34. doi:10.1136/medhum-2016-011040 5. Brown, A. (2017). Psychological Benefits of Art Therapy - Canadian Counselling and Psychotherapy Association. [online] Canadian Counselling and Psychotherapy Association. Available at: https://www.ccpa-accp.ca/psychological-benefits-of-art-therapy/ [Accessed 30 Nov. 2017]. 6. Junne, F., & Zipfel, S. (2016). The art of healing: art therapy in the mental health realm. The Lancet Psychiatry, 3(11), 1006-1007. doi:10.1016/s2215-0366(16)30210-3 7. Malchiodi, C. (2017). Art Therapy’s Achilles Heel. [online] Psychology Today. Available at: https://www.psychologytoday.com/blog/arts-andhealth/201404/art-therapy-s-achilles-heel [Accessed 30 Nov. 2017].

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Towards the Establishment of Deep Brain Stimulation for Neuropsychiatric Disorders By Marietou Daou

Deep Brain Stimulation (DBS) involves implanting electrodes in the brain to electrically stimulate axons and dendrites in deep brain structures1. The most basic DBS system consists of a series of electrodes placed by neurosurgery in the deep brain grey matter. Then, they are connected by a wire to a battery-operated pulse generator implanted under the skin in the abdomen or the chest². DBS has been widely used for the treatment of Parkinson’s disease and other movement disorders. In Parkinson’s disease, the stimulation of the subthalamic nucleus and some basal ganglia nuclei can successful“THE PROMISING APPLICATIONly alleviate symptoms. OF DBS IN NEUROPSYCHIATRICThis electriDISORDERS LIES IN THE FACTcal stimula-

tion technique results in neuromodulation that can target pathological pathways and rapidly reduces symptoms, such as tremor, rigidity, bradykinesia, stance and gait impairments and speech disturbances¹. However, when it targets the mechanisms involved in synaptic plasticity and anatomy remodelling it reduces symptoms more slowly¹. This difference in response to DBS is also due to the fact that DBS works in different ways. Firstly, DBS can work as a reversible lesion¹: the stimulating electrode inhibits the soma of neurons, causing a hyperpolarizing current that prevents initiation or propagation of the action potential and consequentially reduces of hyperkinesia seen in Parkinson’s1. Additionally, DBS can work by impacting the syn-

THAT IT PROVIDES THE POSSIBILITY OF TARGETING SMALL CONFINED AREAS AND CIR-apse as well, by stimulating the release of GABA from the presynCUITS OF INTEREST”

aptic terminal, thereby resulting in another inhibitory pathway to reduce hyperkinesia¹. Overall, there are multiple observations of DBS causing axonal neuronal activity that results in increased regional action potential frequency output and dissociation from inhibited somatic activity¹. The last known mechanism of action of DBS is through antidromic action potentials (propagated backwards from the axon terminal to the soma) that are responsible for signaling from the basal ganglia nuclei back to the cortex¹. Overall, DBS seems to be effective in treating diseases like Parkinson’s by regularizing neuronal activity¹, and this is something that can be

applied in the treatment of neuropsychiatric disorders. For instance, neurosurgeon Emad Eskandar performs DBS on treatment-resistant obsessive-compulsive disorder (OCD) patients. In these patients, DBS reduces obsession and compulsion symptoms by targeting the pathway that connects motivation areas to the frontal cortex². Also, a recent pilot study conducted by Laura Salgado Lopez looked into the treatment of refractory schizophrenia using DBS. Although this prospective study is still in its preliminary stages, the patients reported improved social isolation and auditory hallucination symptoms³. The promising application of DBS in neuropsychiatric disorders lies in the fact that it provides the possibil-

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ity of targeting small confined areas and circuits of interest; this seems especially encouraging given the large proportion of ineffective treatments and side effects caused by pharmacologic drugs². The next step is to fully understand the molecular and cellular underpinnings neuropsychiatric disorders². It would also be useful to construct a device capable of not only stimulating the brain but also monitoring it to detect unpredictable changes possibly corresponding to the intermittent episodes characterizing disorders such as post-traumatic stress disorder (PTSD) or schizophrenia². Another element to consider is that many psychological disorders affect multiple anatomical locations and manifest themselves in a multifactorial fashion in unique phenotypes patients from patient². A research team led by Dr. Eskandar is already working on developing a DBS treatment tailored to the individual, where electrodes would be placed according to

symptoms and neuroanatomy of the patient²; this could possibly result in effective treatment of depression, PTSD and generalized anxiety disorder². Nonetheless, there are concerns that arise from DBS that should not be neglected. Some issues include, but are not limited to, the cost of maintaining the devices after the trial ends, or the unfairness of removing the devices at the end of a failed study given the invasiveness of the procedure⁴. Some patients also reported or worsening of symptoms after the generator is switched back off³. Likewise, the long-term effects of DBS are still unknown⁴ and possible complications related to surgery³ need to be considered. Therefore, while developments in DBS therapy seem to effectively treat neuropsychiatric disorders, further research has to resolve the ethical and technical issues related to it.

Image source: National Pain Report

References 1. Herrington TM, Cheng JJ, Eskandar EN. Mechanisms of deep brain stimulation. Journal of Neurophysiology. 2016;115(1):19-38. doi:10.1152/jn.00281.2015. 2. Adam Piore. “A shocking way to fix the brain”. MIT Technology Review. October 8 2015 https://www.technologyreview.com/s/542176/ a-shocking-way-to-fix-the-brain/ 3. American Association of Neurological Surgeons (AANS). "A pilot study of deep brain stimulation in treatment-resistant schizophrenia." ScienceDaily. ScienceDaily, 25 April 2017. <www.sciencedaily.com/releases/2017/04/170425153818.htm>. 4. Underwood E. “Researchers grapple with the ethics of tetsing brain implants” Brain & Behavior, Scientific Community, October 31 2017 doi:10.1126/science.aar3698

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Biomarkers in Neuropsychiatry Psychiatric disorders are genetically complex. There is no one specific contributing alteration that causes the illness. The traditional method of diagnosing psychiatric disorders is by utilizing the description of symptoms given by patients or their family members. This method of diagnosing is unreliable because of how subjective the interpretation of symptoms is: how patients interpret their symptoms is different from how a family member or mental health professional would interpret them. Moreover, one’s culture and society further influences their willingness to talk about such a sensitive issue1. With the use of biomarkers, the goal is to diagnose, not only more accurately but also diagnose the patient earlier on. This would allow for early intervention, as many studies have shown that early intervention is the key to treating patients effectively. As of now, there are no approved clinical tests to diagnose for psychiatric disorders, unlike many other illnesses. However, the National Institutes of Mental Health has proposed the usage of Research Domain Criteria (RDoC), which is classifies illness based on neurobiological and observational behavioral measures. Unlike other diagnostic handbooks, RDoC’s goal is to classify mental illness from a quantifiable biological perception and observable behaviour1,2. RDoC is focused on isolating genes, cells, circuits, molecules or physiological measures

References

Tanya Khimani that would be linked with distinct cognitive constructs across various systems2. RDoC will not be replacing the current method of diagnosing completely but it would enhance the current system1. Various other organizations are looking at solutions for psychiatric illnesses from different perspectives by characterizing the genetic link to mental illness, which would help in the identification of biomarkers of psychiatric disorders. Some other interesting approaches involve using proteomics and metabolomics to analyze blood based biomarkers, or analyzing the gut microbiome. Genomics and transcriptomics studies have already shown positive results; it has led to the identification of transcriptional profiles and genetic loci linked to many mental health disorders such as autism spectrum disorders, major depressive disorder, schizophrenia, etc. Another benefit of using biomarkers is that it allows for advent of personalized medication, giving physicians the opportunity to monitor the response of the patient to the medication or therapy prescribed. This would allow the treatment to be made to the individual’s needs and will allow the patient to be effectively treated1.

1. “Biologically-Inspired Biomarkers for Mental Disorders.” EBioMedicine 17 (2017): 1–2. PMC. Web. 18 Nov. 2017. 2. Abi-Dargham A, Horga G. “The search for imaging biomarkers in psychiatric disorders.” Nature Medicine. 2016;22(11):1248-1255.

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By Lucy Lu

An Interview with Dr. Freda Miller Dr. Freda Miller is a senior scientist at the Sick Kids Hospital and a professor at the University of Toronto. Her work centers on cellular mechanisms that regulate development of the mammalian nervous system, particularly regarding neuronal growth, survival and apoptosis. Dr. Miller is best known for her discovery of skin-derived precursors (SKPs), stem cells in skin that can form neural cells that may be useful in treatment of brain injuries or neurodegenerative diseases. Q1: DID YOU GO INTO (SKP) RESEARCH TO SOLVE THE ETHICAL ISSUE OF EMBRYONIC STEM CELLS? Yes. At the time, everyone was thinking in very defined frames. A bone stem cell only gives rise to bone, or a neural stem cell only to neurons. It was a complete shock when something grew, like it was almost too good and weird to be true. I’d like to think our work set the stage for other discoveries, like induced pluripotent stem cells (IPS). Q2: HAVE YOU MADE ANY ADVANCEMENTS ON SKPS SINCE THE 2009 DISCOVERY? We went two directions with them. One was to try to use them therapeutically, the other was find out why we have them in the first place. A collaboration with UBC led to a series of rat spinal cord experiments. We saw acute and chronic injuries models regain anatomical and functional repair. We tried to take this to humans but it’s proving difficult to harvest enough cells given the size of our spinal cords. The second direction of

what function they serve led to the discovery that they are stem cells that normally fix your dermis. So maybe if they can promote endogenous repair we can artificially induce this process. Repurposed small molecule drugs have shown to promote rodent skin wound healing, and this is now a company piloting in humans as well. Another fun side project its led to is digit tip regeneration. Like salamanders, humans can also regenerate, but only in our fingertips. This is a whole new field; not many people in the world are doing this. But that’s science – if it’s a good question, you follow it. Q3: METFORMIN IS A COMMONLY PRESCRIBED DIABETES DRUG. HOWEVER, STUDIES ARE BEGINNING TO SHOW ITS POSSIBLE ROLE IN NEUROGENESIS, STROKE RECOVERY, AND OTHER BRAIN PATHOLOGIES. YOU PUBLISHED A PAPER IN 2012 ILLUSTRATING THE PROMOTION OF NEUROGENESIS AND SPATIAL MEMORY FORMATION USING METFORMIN, AND ANOTHER 2015 PAPER ON THE MOLECULAR PATHWAYS IMPLICATED. FOLLOWING THIS AND OTHER CONTRIBUTING RESEARCH, THE NEXT STEP SEEMED TO BE BRINGING THIS

TO CLINICAL TRIALS. WHERE HAS METFORMIN GONE SINCE THEN? HAS A CLINICAL TRIAL BEEN STARTED?

Yes! A pilot project is wrapping up now, looking at acquired brain injuries from brain tumors in children. These kids end up getting cranial radiation for the tumor and grow up with decreased cognitive development. You can actually see the hippocampus, an area of neurogenesis, is smaller later on. We also found that the white matter is thinner, so the myelination is less. Related to that, Dr. Cindi Morshead showed Metformin causes oligodendrocyte-genesis. This trial is looking at kids with problems in their myelination from diseases like multiple sclerosis. It uses eye tracking machines to measure reaction time and therefore the demyelination in their visual system, while being very non-invasive. This is exciting because it allows earlier intervention. New studies are showing myelin is not static but changes with learning. So, if we can rescue and remyelinate, oligodendrocytes might be a more realistic target than

INTERNEURON

neural regeneration. Q4: METFORMIN SOUNDS LIKE A MIRACLE DRUG. DO YOU HAVE ANY RESERVATIONS ON ITS USE? Right now, we basically have nothing for neurological disease. So, if you can develop something for even a population of these patients that’s something. Metformin is so off-patent and cheap, and it’s been used in 2 to 100-yearolds, primarily to treat diabetes and metabolic disorders. So far, I think it’s as safe or safer than aspirin. There’s been proof of its anti-cancer properties, but now people are even taking it just as an anti-aging agent.

Q5: WHO IS YOUR DREAM COLLABORATOR? Depends on the project. Generically, someone who is as excited as you, rigorous in their work, has complimentary expertise, and often overlooked, does what they say they will do. Q6: IF YOU WERE A YOUNG NEUROBIOLOGIST STARTING OUT TODAY, WHAT WOULD YOU STUDY? I would either stay in the molecular biology field, where there are lots of discoveries happening. Or go into something completely different, like systems circuitry or cognitive

neuroscience. My advice for young scientists is to go into a relatively unexplored area, with some foundation though, and make breakthroughs there. I really believe this is the golden age of biology. The field is just exploding. A good quote but I can’t find anywhere to fit it: “One of the ways you know you’re a scientist. The pure excitement of just wanting to know the answer, even when it’s not your work.”

To conclude, after my interview with Dr. Miller, metformin really seems like a miracle drug in all regards, with more benefits being elucidated in this golden age of biology. With this clinical trial wrapping up, it will be exciting to see what impacts metformin can have in the real-world setting. Keep an eye out for the results of this trial come 2018 – perhaps metformin will soon become a commonplace preventative prescription.

Volume 5. Issue 2. December 2017

NAUS

Everything Neuroscience Conference Amar Dohlakia Saturday, November 4, 2017 marked the date of the highly anticipated Everything Neuroscience conference. Put together by none other than the hardworking NAUS executive team, the 6th annual symposium featured a research presentation and discussion with neuropsychiatry experts, followed by an undergraduate poster competition, and individualized “breakout sessions”. The event allowed a platform for the exhibition of modern research advances in the field of neuropsychiatry as well as an excellent opportunity for a diverse crowd of participating students to further their academic, social, and professional development. The day kicked off with the keynote presentation delivered by Dr. Jane Foster from McMaster University. In her presentation, she discussed crucial mutual links concerning the human microbiome and one’s mental state and wellbeing. Dr. Foster presented a variety of studies and research investigating the influence and importance of bacteria on a multitude of psychological outcomes, including hypothalamic secretion of cortisol, and parallels between the bacteriome and connectomes. Following Dr. Foster were Dr. Voineskos and Dr. Liu both from the Center for Addiction and Mental Health. Dr. Voineskos discussed novel brain stimulation technologies and their potential to deeply impact how we can potentially treat mood disorders. Dr. Voineskos’s take home message suggested that research may be on the brink of engineering and honing portable, non-invasive treatment, all accessible from the family room couch. Dr. Liu discussed her team’s links discovery of potential biomarkers using rodent models that may be re-

lated to the development of PTSD. She hopes that her research may be used in the future development of a PTSD treatment or therapy. Following a panel discussion, students were afforded the opportunity to attend a more intimate, individualized “breakout session”, where participants were able to network with professionals after a short presentation. The Interneuron was fortunate enough to attend the Obsessive Compulsive Disorder session, led by Dr. Gwyneth Zai, and Dr. Atwells. The trailblazing Dr. Atwells presented her work on inflammation in the neurocircuitry of OCD. Inspired by potential to use immunomodulatory treatments for OCD treatment, Dr. Atwells explored trends in inflammatory markers such as microglial activation and TSPO release in patients with OCD. She ultimately suggested that a treatment of OCD can be developed by evoking a shift from greater M1 inflammatory (microglia) activity to M2 (neuroprotective) activity. Culminating the conference, NAUS announced the results of the undergraduate poster contest, Safa Ansar. Safa explored the bases of associative learning and serotonin signaling in the C. elegans model, and concluded that even in the absence of five serotonin receptors, the worm was able to be conditioned in presence of an aversive stimuli. For her work, she was awarded a newly minted NAUS backpack, courtesy of the co-presidents. NAUS hosted yet another engaging and insightful installment of the Everything Neuroscience conference. The editors at the Interneuron would like to thank NAUS once again for their tireless effort in organizing such a successful event as well as giving us the opportunity to participate, network, and cover the conference. 27

Image source: pngtree

INTERNEURON

SSSCR Presents:

Stem Cells - Extending the Frontiers of Knowledge Avani Krishnan

Canada has always been at the very forefront of stem cell research. From being currently used for bone marrow transplants to treat cancers such as leukemia to recent clinical trials that use neural stem cells to treat spinal cord injuriesÂš, stem cells have the capacity to repair and mend our bodies. It is safe to say that the field is a stepping stone to transforming and restructuring health care as we know it. The prospects of stem cells seem quite straight forward, but one aspect remains unclear to the majority of the public-what is a stem cell? Stem cells are immature blood cells that have the ability to self-reproduce and differentiate into different types of tissues and cells. For example, a type called mesenchymal stem cells. that you can get from marrow or umbilical cords, can differentiate into red blood cells, white blood cells or plateletsÂ˛. Unlike specialized cells, such as muscle cells, that lack the ability to replicate and replace themselves, stem cells can divide and produce identical copies of themselves and has the ability to do so throughout the life of an organismÂł. In other words, stem cells replace damaged cells that our bodies cannot replace naturally. Stem cell research is only at its early stages of growth. However, by dwelling into this field, we can succeed in various therapeutic fields such as regenerative medicine since stem cells have the potential to create new cells, tissue and organs that can be used for transplantation, in turn saving millions of lives. With that being said, SSSCR would like to invite you to our annual Stem Cells ConReferences

ference, which will be held on January 27, 2018 at the Bahen Centre for Information Technology. The Student Society for Stem Cell Research, or SSSCR, is an international network dedicated to the advancement of scientific research for cures. The daylong conference will encompass the many advancements towards the improvement of medicine using stem cells. It will imbue the discoveries and progress in stem cell research, specifically pertaining to ethics, policies, innovation, publication and technology. Researchers from a variety of hospitals and institutions in Toronto will be invited to present their current work to an expected audience of 350 on the topic of stem cells and how it has pioneered a number of innovative techniques. In addition to researchers, graduate students will also be invited to present their research. Furthermore, speakers will have the opportunity to conduct smaller-scale discussions focusing on specialized subjects within the field. Ultimately, the day will conclude with a panel discussion examining leading issues involving the use of stem cells in medicine. This conference will provide a unique opportunity for attendees to expand their knowledge surrounding the principles of stem cell research and to make valuable connections with professionals in the field, all the while gaining valuable insight in the success stem cells research has had in extending the frontiers of knowledge. Follow us on twitter @ssscr_toronto and our Facebook event page Stem Cells: Frontiers to get updates about the conference and ticket information.

1. Morsehead, Cindi M. et al (1994). Neural Stem Cells in the Adult Mammalian Forebrain: A Relatively Quiescent Subpopulation of Subependymal Cells. Neuron, 13(5), 1071-1082. 2. Bayramova, AN (2017). The Role of Stem Cells of the Basal Layer of Endometrium in Gynaecological Diseases. Critical Care Obstetrics and Gynecology, 3(13). 3. Types of Stem Cells and Their Uses. (n.d.) Retrieved November 13, 2017, from https://www.eurostemcell.org/types-stem-cells-and-their-uses#collapse468

Volume 5. Issue 2. December 2017

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