The 2020 International Mental Health Research Virtual Symposium
This available to watch free On-Demand at https:// www.bbrfoundation.org/event/ international-mental-health-researchsymposium
The BBRF Outstanding Achievement Prizes acknowledge and celebrate the power and importance of neuroscience and psychiatric research in transforming the lives of people living with mental illness. The recipients of this year’s awards are recognized for their research achievements in suicide prevention, schizophrenia, autism, bipolar disorder, childhood trauma and cognitive neuroscience.
Dr. Jeffrey Borenstein, BBRF’s President & CEO, notes that “These exceptional scientists are on the cutting edge of finding new treatments, cures, and methods of prevention for mental illness. We celebrate their progress in brain and behavior research, which is paving the way for more people to live full, happy, and productive lives.”
Dr. Herbert Pardes, President of the BBRF Scientific Council, provides opening remarks for the Symposium and observes that the 2020 Outstanding Achievement Prizewinners are “making extraordinary contributions to advancing psychiatric research and eliminating the stigma of mental illness. Their work is providing insights in our understanding of the brain and how to treat and potentially cure psychiatric disorders.”
An overview of the entire Symposium is provided by Dr. Robert Hirschfeld, a BBRF Scientific Council member who has served as the moderator at the in-person Symposium for more than 30 years.
The symposium program features the prize-winning scientists each speaking for about 20 minutes as they take the audience through slides explaining their research results. In the four pages that follow, we summarize the subjects covered in each Symposium talk.
Anne S. Bassett, M.D., delivers a Symposium talk entitled Identifying A Genetic Subtype of Schizophrenia That is Clinically Relevant for Patients and Families. Dr. Bassett is Professor of Psychiatry & Director of the Clinical Genetics Research Program at the University of Toronto and the Centre for Addiction & Mental Health, and a 2002 BBRF Distinguished Investigator and 1997 BBRF Independent Investigator.
Her presentation highlights some of the technological advances making it possible to identify genetic changes with high impact that are clinically relevant for patients with schizophrenia and their families. These genetic changes, identifiable with a clinical blood test, can influence clinical care and are having important effects on our understanding of schizophrenia. Dr. Bassett is known for her work with individuals born with a piece missing from a section of chromosome 22, who have a one-in-four chance of developing schizophrenia. She has pioneered the world’s first clinic devoted to adults with the associated 22q11.2 deletion syndrome. Dr. Bassett says that for schizophrenia in general, such a human model provides enhanced power to understand the interacting factors and mechanisms that lead to the illness and their relationship to other brain disorders, as well as contribute to new animal and cellular models for study.
Symposium speaker Melissa Gymrek, Ph.D., discusses Dissecting the Role of Repetitive Regions of the Genome in Schizophrenia and Autism. An Assistant Professor in the Departments of Medicine and Computer Science & Engineering at the University of California San Diego, Dr. Gymrek’s major research interest is to understand complex genetic variants underlying changes that lead to human disease. Her recent work focuses on repetitive DNA variants known as short tandem repeats (STRs), which she has utilized as a model for complex genetic variation. She develops computational methods for analyzing and visualizing complex variation from large-scale sequencing data. These tools are allowing researchers for the first time to answer many questions regarding STRs and other variant types, including their contribution to neuropsychiatric disorders in humans In her lecture, Dr. Gymrek notes that repetitive regions of the genome are one of the largest sources of genetic variation across human populations and are well known to contribute to human traits. She observes that large sequencing efforts have largely ignored repeats, owing to the technical challenges they present. Hence, her team and others have sought to develop bioinformatics methods for analyzing genomic repeats at population scale. She explains her team’s efforts to integrate analysis of repeat variants into genome-wide association studies as well as wholegenome sequencing studies. This research identifies novel risk areas in the genome, called risk loci, and demonstrates that genetic variation at repeat sequences plays a key, but often overlooked, role in neuropsychiatric traits including schizophrenia and autism spectrum disorders.
Martin Alda, M.D., FRCPC, discusses Thinking Rationally about the Treatment of Bipolar Disorder in his Symposium talk. A Professor of Psychiatry and Killam Chair in Mood Disorders at Dalhousie University, and a 2003 and 1999 BBRF Independent Investigator, Dr. Alda has worked at the junction of clinical and basic research, investigating genetic and neurobiological markers of mood disorders and response to treatment. His clinical, genetic, pharmacogenetic, and brain imaging studies are based on carefully characterized prospective clinical samples.
The aim of his lab is to develop methods of personalized treatment in psychiatry. Dr. Alda points out that most people with bipolar disorder require ongoing treatment to prevent recurrence of mania and depression. While several medications have been found to be effective in this indication, each works only in a proportion of patients, he stresses. The treatment in individual patients is usually chosen by trial-and-error, with each trial taking many months. As a result, he notes, most people achieve stability after a considerable amount of time. He discusses how his research guides the way to rational selection of longterm treatment. Starting with the “gold-standard” mood stabilizer, lithium, his team has shown that the response to it has a genetic basis and can be predicted reliably with a combination of clinical and genomic data. They have also shown that patients who respond to a different class of medications called anticonvulsants differ from lithium responders in important clinical features. It is the goal of their work, he suggests, to help institute early and effective treatment, shorten the time to full recovery, and reduce the negative impact of the illness.
Gustavo Turecki, M.D., Ph.D., speaks about How Pain Shapes the Brain: The Impact of Childhood Trauma on Suicide Risk. Professor and Chair of Psychiatry at McGill University, Dr. Turecki is a 2016 BBRF Distinguished Investigator, 2008 BBRF Independent Investigator, and 2000 BBRF Young Investigator. Pioneering research he has led has increased our understanding of how traumatic life experiences impact gene function in brain cells and increase long-term risk for suicide by regulating critical genes involved in stress responses and behavioral development.
He discusses how childhood experiences have an important impact on the way emotional and behavioral brain processes are regulated. Childhood maltreatment or abuse, for instance, increase the likelihood of negative mental health outcomes, including increased risk of suicide over the lifespan. Dr. Turecki also discusses data from his research suggesting that childhood maltreatment leads to differential molecular regulation of a number of key brain molecular pathways. In turn, he suggests, these changes associate with differential behavioral and emotional trait regulation, which increases the risk of suicidal behavior.
Joan L. Luby, M.D., devotes her Symposium discussion to the question of How Early Childhood Experiences Shape Brain Development and Influence Mental and Physical Health Trajectories. Dr. Luby is Samuel and Mae S. Ludwig Professor of Psychiatry (Child) at Washington University School of Medicine. She is a member of the BBRF Scientific Council; a 2008 and 2004 BBRF Independent Investigator; the 2004 BBRF Klerman Prize winner for Exceptional Clinical Research; and a 1999 BBRF Young Investigator.
Dr. Luby’s presentation reviews how early experience alters brain development—either for benefit or detriment—during sensitive periods. She notes the importance of caregiver nurturance on healthy brain development and how a more detailed understanding of sensitive periods can be used to harness proactive prevention and health enhancement strategies. Her talk underscores the power of the early psychosocial environment on child health and well-being and in setting lifelong health trajectories.
The Symposium talk given by Angela Roberts, Ph.D., addresses Prefrontal Circuits That Regulate Threat and Reward-Elicited Behaviors. Dr. Roberts, Professor of Behavioral Neuroscience and Professorial Fellow at Girton College, University of Cambridge, UK, combines pharmacological, cardiovascular, neuroimaging, and genetic techniques to understand the brain basis of cognition and emotion. Her lab has worked to establish non-human primate models of positive and negative emotion regulation and trait anxiety.
Dr. Roberts has revealed distinct prefrontal cognitive processes that may underlie the varied causation of affective disorders and has elucidated the role of dopamine- and serotonin-system modulation of these processes that are essential for the more effective targeting of current pharmacotherapies. In her talk, Dr. Roberts discusses what happens when there is an inability to regulate emotions—a core symptom of many psychiatric disorders including anxiety and depression and often associated with altered activity of neurons in the brain’s prefrontal cortex. She explains that to further our understanding of its role in the prefrontal cortex’s failure to regulate response to reward and threat in mood and anxiety disorders, her team is studying threat and reward-elicited behaviors in the marmoset, a primate. These studies are revealing the multiple dysregulated pathways and distinct cognitive impairments within the prefrontal cortex, as well as mechanisms of action of current treatments, providing insight into the probable multiple causes of, and hence potentially differential treatment strategies for, anxiety and depression.
Robert Desimone, Ph.D., speaks at the Symposium about A Causal Analysis of the Attentional Network. The Doris and Don Berkey Professor of Neuroscience at the Massachusetts Institute of Technology and Director of the McGovern Institute for Brain Research, Dr. Desimone studies how the brain deals with the challenge of information overload. By studying the visual system of humans and animals, he has shown that when we attend to something specific, neurons in parts of the brain concerned with vision filter out distracting information, allowing us to concentrate on the task at hand. This visual filtering is under the control of parts of the brain, including prefrontal cortex, concerned with “executive function,” working memory, and the control of sensory processing.
Dr. Desimone’s discussion explores emerging insights from human and animal data about the network that supports attentive vision. He notes that the most behaviorally relevant stimuli in scenes we observe are selected for processing and control over behavior. The effects of selection on neuronal responses are widespread, he says, making it difficult to distinguish cause from effect in the attentional network. However, he suggests, the flow of control can be inferred through an analysis of the relative timing of neural signals and the use of methods such as pharmacological inactivation, optogenetics, and feedback training to establish the impact of one circuit upon another.
Also presenting at the BBRF Symposium is Myrna M. Weissman, Ph.D., a recipient of the 2020 Pardes Humanitarian Prize in Mental Health. Dr. Weissman devotes her Symposium discussion to Thirty Years of Studying Families at Risk for Depression: What Have We Learned? Dr. Weissman is Kemper Family Professor of Epidemiology in Psychiatry at the College of Physicians and Surgeons & Mailman School of Public Health, Columbia University, and Chief of the Division of Epidemiology at the New York State Psychiatric Institute.
Dr. Weissman’s talk summarizes an historic multi-decade study she has led that has analyzed the impact over three generations of major depressive disorder, and notes the role of these findings in humanitarian work in which she has been involved. Overall, Dr. Weissman’s work has shown that depression usually begins early in life; tends to recur in many people; runs in families; and is often highly amenable to treatment, with evidence-based methods. Her multi-generation study calls attention to differences in outcomes, focusing on families at high and low risk for depression. One important discovery of the study concerns the impact of maternal remission from depression upon offspring. The child of a parent who is depressed has a much higher risk of depression over the lifespan, Dr. Weissman notes. This is also true in families in which a child’s parent and a grandparent have suffered from depression. But Dr. Weissman’s research has demonstrated the power of treatment. For instance, if a depressed mother is promptly treated, with antidepressant medicines or psychotherapy or both, and her symptoms remit within 3 months, the studies show clearly that her children usually fare better as well.
Written By Peter Tarr, Ph.D.