Advances in the Neurobiology of Mental Illness

Advances in the Neurobiology of Mental Illness

Friday, October 7, 2016

The New York Academy of Sciences

Presented By

The New York Academy of Sciences

 

Mental health disorders can cause debilitating consequences on quality of life for individuals, families, and society. The World Health Organization has reported that mental illnesses are the leading causes of disability worldwide, accounting for 37 percent of healthy years lost from non-communicable diseases. Depression alone accounts for one third of this disability.

This symposium will provide a neutral forum for scientists, physicians, clinicians, other allied healthcare providers, policy makers, and patients across a range of scientific, clinical, industry, and government sectors to explore new scientific understanding of the neurobiology (including genetics, neurocircuitry, and neuroimmune mechanisms) of a range of mental illnesses. Plenary presentations will focus on schizophrenia, major depression, eating disorders, and childhood-onset psychiatric disorders such as autism. In addition to exploring the basic science underlying these illnesses, the symposium will also explore avenues for translating the basic science into treatments, new tools and technologies, and innovative ways to provide overall optimal care for this patient population.

Registration

Registration for the in-person event is Sold Out. However, space remains for the simulcast Webinar. Registration for the Webinar is free.

Please note: Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar.

Agenda

* Presentation times are subject to change.


Friday, October 7, 2016

8:00 AM

Registration and Breakfast

9:00 AM

Welcome and Introductory Remarks
Melanie Brickman Borchard, PhD, MSc, The New York Academy of Sciences

9:15 AM

Overview: State of the Science in Mental Illness
Husseini Manji, MD, FRCPC, Janssen Research & Development, LLC

9:50 AM

Audience Q&A

10:00 AM

Medical Consequences of Depression and Neuroimmune Interactions
K. Ranga Rama Krishnan, MBBS, Rush Medical College

10:30 AM

Audience Q&A

10:40 AM

Networking Coffee Break

11:10 AM

Prediction and Prevention of Psychosis: The Schizophrenia Prodrome
Tyrone D. Cannon, PhD, Yale University

11:40 AM

Audience Q&A

11:50 AM

Rapid Relief from Severe Depression and Suicidal Ideation Within Hours: from Synapses to Symptoms to New Treatments
Carlos A. Zarate Jr., MD, National Institute of Mental Health, U.S. National Institutes of Health; The George Washington University
 
* Dr. Zarate will not be participating in the webinar *

12:20 PM

Audience Q&A

12:30 PM

Networking Luncheon

1:45 PM

Innovative Tools Utilized as Biomarkers and Clinical Indicators in Autism Spectrum Disorder
Geraldine Dawson, PhD, Duke University School of Medicine
 
* Dr. Dawson will not be participating in the webinar *

2:15 PM

Audience Q&A

2:25 PM

Using Neuroscience to Inform Clinical Thinking: Applications in Pediatric Anxiety
Daniel S. Pine, MD, National Institute of Mental Health, U.S. National Institutes of Health

2:55 PM

Audience Q&A

3:05 PM

Networking Coffee Break

3:35 PM

The Emerging Neurobiology of Anorexia Nervosa
B. Timothy Walsh, MD, New York State Psychiatric Institute, Columbia University

4:05 PM

Audience Q&A

4:15 PM

Harnessing Mobile and Sensor Technology to Help Patients with Diseases of the Brain and Central Nervous System
Vaibhav Narayan, MBA, PhD, Janssen Research & Development, LLC

4:45 PM

Audience Q&A

4:55 PM

Closing Remarks

5:00 PM

Symposium Adjourns

Speakers

Tyrone D. Cannon, PhD

Yale University
website

Tyrone D. Cannon is the Clark L. Hull Professor of Psychology and Psychiatry at Yale University. Dr. Cannon earned his bachelor's degree at Dartmouth College (1985) and his doctoral degree at the University of Southern California (1990). He took his first academic appointment in the Department of Psychology at the University of Pennsylvania, where he advanced to Associate Professor. He joined the faculty at University of California Los Angeles in 1999 as Professor of Psychology and Psychiatry and Biobehavioral Sciences, before moving to his current position at Yale in 2012. Dr. Cannon's research addresses the interplay between psychological-level phenomena and neurobiological mechanisms as they relate to disturbances of perception, belief, motivation, and emotional processing in people with mental illness, principally schizophrenia. He pursues these themes in a variety of contexts, including longitudinal studies of at-risk populations and patients in various phases of illness and studies of twin-pairs concordant and discordant for these illness phenotypes. A primary aim of his work, which incorporates structural, functional, metabolic, and neurochemical brain imaging, as well as behavioral and genetics approaches, aims to identify the mechanisms underlying the emergence of psychosis during adolescence and early adulthood and to develop effective intervention and prevention strategies targeting these mechanisms.

Geraldine Dawson, PhD

Duke University School of Medicine

Geraldine Dawson is Professor, Departments of Psychiatry and Behavioral Sciences, Pediatrics, and Psychology and Neuroscience and Director of the Duke Center for Autism and Brain Development at Duke University, North Carolina. Dr. Dawson is President of the International Society for Autism Research. She serves as a member of the U.S. National Institutes of Health Interagency Autism Coordinating Committee, which develops the federal strategic plan for autism research, services, and policy. Dr. Dawson is an expert on autism, having published over 250 articles and 10 books on early detection and treatment of autism and brain development. Dr. Dawson is a Fellow of the American Psychological Society and American Psychological Association. Dr. Dawson's awards include a Lifetime Achievement Award from the Association for Psychological Science for outstanding contributions to the area of applied psychological research addressing a critical problem in society at large, among others. Her scientific research was recognized by the National Institutes of Health as a Top Advance in Autism Research in 2007, 2008, 2009, 2010, 2012, 2013, 2014, and 2015, and by TIME magazine as one of the top 10 medical breakthroughs of 2012. Dawson received a PhD in Developmental and Child Clinical Psychology from University of Washington and completed a clinical internship at the University of California, Los Angeles Neuropsychiatric Institute.

Husseini Manji, MD, FRCPC

Janssen Research & Development, LLC

Husseini K. Manji, MD, FRCPC, is the Global Therapeutic Head for Neuroscience at Janssen Research & Development, LLC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. He was previously Chief, Laboratory of Molecular Pathophysiology & Experimental Therapeutics, United States National Institutes of Health (NIH), and director of the NIH Mood and Anxiety Disorders Program, the largest program of its kind in the world. He is also a visiting professor at Duke University.

Dr. Manji received his BS (Biochemistry) and MD from the University of British Columbia. Following residency training, he completed fellowship training at the U.S. National Institute on Mental Health and obtained extensive additional training in cellular and molecular biology at the U.S. National Institute of Diabetes and Digestive and Kidney Diseases. The major focus of his research has been the investigation of disease- and treatment-induced changes in gene and protein networks that regulate synaptic and neural plasticity in neuropsychiatric disorders. His work has helped to conceptualize these illnesses as genetically-influenced disorders of synaptic and neural plasticity, and has led to the investigation of novel therapeutics for refractory patients. He has also been actively involved in the development of biomarkers to help refine these multifactoral diseases into mechanism-based subcategories to develop targeted therapeutics.

Vaibhav Narayan, MBA, PhD

Janssen Research & Development, LLC
website

Dr. Vaibhav is Senior Director, Neuroscience Therapeutic Area at Janssen R&D and currently Head of Neuroscience Integrated Solutions and Informatics at Janssen Pharmaceutical Companies of Johnson & Johnson, where his group is developing science-based, technology-enabled solutions for early diagnosis, relapse prediction, and adherence management in Alzheimer's disease, depression, and schizophrenia. Vaibhav joined Johnson & Johnson from Eli Lilly and Co., where he was the Head of Discovery and Medical Informatics group. Prior to Lilly, Vaibhav held multiple leadership roles at Celera Genomics where he participated in the sequencing, assembly, and analysis of the human genome. Vaibhav obtained his PhD from Yale University jointly from the Departments of Chemistry and Molecular Biophysics & Biochemistry in 1998, and an Executive MBA from Kellogg School of Management, Northwestern University in 2009.

Daniel S. Pine, MD

National Institute of Mental Health, U.S. National Institutes of Mental Health
website

Daniel S. Pine, MD, is Chief, Section on Development and Affective Neuroscience, in the National Institute of Mental Health Intramural Research Program. Pine moved to this position in 2000, after 10 years of training, teaching, and research at Columbia University. Since graduating from medical school at the University of Chicago, Pine has been engaged continuously in research on pediatric mental disorders, as reflected in more than 400 peer-reviewed papers. Currently, his group examines the degree to which pediatric mood and anxiety disorders are associated with perturbed neural circuitry function. Pine served as the chair of the Psychopharmacologic Drug Advisory Committee for the Food and Drug Administration, chair of the Child and Adolescent Disorders Work Group for the DSM-5 Task Force, and president of the Society of Biological Psychiatry. He is a member of the Institute of Medicine of the National Academy of Sciences and has received many other awards.

K. Ranga Rama Krishnan, MBBS

Rush Medical College
website

K. Ranga Rama Krishnan, MBBS, is the Dean of and senior vice president of Rush University Medical Center. Krishnan most recently served for seven years as the dean at the Duke–NUS Graduate Medical School Singapore, and previously as the school's executive vice dean.

Prior to and during his tenure in Singapore, Krishnan was professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center. He was chair of psychiatry at Duke from 1998–2009. The department included more than 490 faculty members who conducted more than 270 studies annually. Krishnan earned his medical degree in 1978 and completed a rotating internship at Government General Hospital and Madras Medical College in Madras, India. He then served as senior house officer at Queen Elizabeth Hospital, University of West Indies, Barbados, West Indies.

He is an elected member of the Institute of Medicine. He has been the recipient of many awards and honors, including: the 2007 Distinguished Scientist Award from the American Association for Geriatric Psychiatry; the 2008 C. Charles Burlingame Award, which recognizes outstanding leadership and lifetime achievement in psychiatric research and education; the Laughlin Fellow from the American College of Psychiatry; The Rafaelsen Fellowship Award, Collegium Internationale Neuro-Psychopharmacologicum; the Distinguished Investigator Award for Genetic Imaging Study in Bipolar Disorder, granted by National Alliance for Research on Schizophrenia and Depression; the research award for mood disorders and the research award for geriatric psychiatry from the American College of Psychiatry; the Gerald Klerman Award for Research in Mood Disorders, Depressive and Bipolar Support Alliance; and the Edward Strecker award from the University of Pennsylvania 2011.

At Duke University, Krishnan created a translational research center focused on depression in the elderly, the only such center in the United States funded by the National Institutes of Health.

B. Timothy Walsh, MD

New York State Psychiatric Institute, Columbia University
website

B. Timothy Walsh, MD, received his undergraduate degree in chemistry from Princeton University and MD from Harvard Medical School. After completing an internship in medicine at Dartmouth College, and a psychiatry residency and research fellowship at Albert Einstein College of Medicine, he joined the Department of Psychiatry at Columbia University. He brought with him an interest in understanding eating disorders that he continues to pursue.

Over the course of his career, he has published several hundred papers, including in Journal of the American Medical Association and the New England Journal of Medicine, and received numerous grant awards from United States National Institutes of Health. He has served as president of both of the major international eating disorders associations, and was a member of both the Diagnostics and Statistics Manual (DSM)-IV and DSM-5 Task Forces for which he chaired the eating disorders work group. He has received awards from the American Psychiatric Association, the Academy for Eating Disorders, the National Eating Disorders Association, and the Association for Behavior and Cognitive Therapies.

At Columbia University, he has held a number of leadership positions, including co-chair of the Institutional Review Board for almost a decade and acting department chair and interim director of the Psychiatric Institute for 18 months. He has been director of the Division of Clinical Therapeutics since its creation in 2007.

Carlos A. Zarate, Jr., MD

National Institute of Mental Health, U.S. National Institutes of Health; The George Washington University
website

Abstracts

Medical Consequences of Depression and Neuroimmune Interactions
K. Ranga Rama Krishnan, MBBS, Rush Medical College, Chicago

When we get a cold, a viral or bacterial infection, we often feel tired lethargic, a bit more sleepy, depressed, and irritable. This constellation of features called sickness behavior is very similar to the features of clinical depression. This behavior is related to the release of proinflammatory cytokines such as Interleukin 6, Tumor Necrosis Factor (TNF), etc. In animal experiments when TNF is centrally administered, it can induce sickness behavior. In humans, significant depression occurs when cytokines and interferons are administered. Major depression is more prevalent amongst patients with conditions that are related to chronic inflammation including psoriasis. The brain circuitry and mechanisms by which proinflammatory cytokines are linked to this behavior have not been fully elucidated. One putative mechanism is the marked reduction of tryptophan that happens when patients are given immunotherapy. This reduction is due to activation indoleamine 2,3 dioxygenase in the liver which can be mediated by TNF and interferons. This activation increases kynurenine which is metabolized in the brain one pathway can lead to production of quinolinic acid that work through the N-methyl-D-aspartate receptors. In a large study of patients with psoriasis using a TNF antagonist, the antagonist was shown to reduce depression and fatigue, supporting the notion that testing proinflammatory antagonists as a potential means of ameliorating depression may be worthwhile.

Prediction and Prevention of Psychosis: The Schizophrenia Prodrome
Tyrone D. Cannon, PhD, Yale University

Subtle changes in belief, thought, and perception appear to precede onset of delusions, formal thought disorder, and hallucinations in the majority of patients with schizophrenia and related disorders. In a young person who is distressed and treatment seeking, onset or worsening of these sub-psychotic features within the past 12 months portends a heightened risk for onset of schizophrenia or a related disorder. This talk will present findings on risk prediction algorithms and potential mechanisms of onset in youth at clinical high risk for psychosis. An independently validated individualized risk calculator is available that incorporates risk factors from clinical, demographic, neurocognitive, and psychosocial assessments to predict likelihood of conversion to psychosis among individuals who meet criteria for a prodromal risk syndrome. At risk individuals who convert to psychosis show a steeper rate of gray matter reduction, most prominent in prefrontal cortex, compared with those who do not. Higher levels of proinflammatory cytokines at baseline predict the accelerated reduction in prefrontal gray matter. These same markers are associated with microglial-mediated synaptic pruning and dendritic retraction in animal models. Processes that modulate microglial activation, such as dysregulated immune function and deficient synaptic plasticity, may represent convergent mechanisms that influence brain dysconnectivity and risk for onset of schizophrenia. This work encourages the development and testing of interventions that target the contributing molecular signaling pathways and that could potentially prevent onset of full symptoms and long-term functional disability in those at elevated risk.

Rapid Relief from Severe Depression and Suicidal Ideation within Hours: From Synapses to Symptoms to New Treatments
Carlos A. Zarate, Jr., MD, National Institute of Mental Health, U.S. National Institutes of Health

Currently approved antidepressant medications for major depressive disorder (MDD) and bipolar disorder act primarily on the monoaminergic system. Unfortunately, these pharmacological agents are efficacious in approximately two-thirds of patients. Glutamate is the major excitatory neurotransmitter in the central nervous system, and the glutamatergic system has been implicated in the pathophysiology of mood disorders. In this lecture, I will review the putative involvement of the glutamate receptor subtypes-N-methyl-D-aspartate (NMDA) and its allosteric sites—α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA), kainate, and metabotropic glutamate receptors (mGluRs)—in the development of novel treatments for MDD as well as preclinical and clinical trials of drugs targeting these receptors. Here, I highlight some of the most interesting results, including: 1) the glycine partial agonist GLYX-13 appears to be effective both as monotherapy and adjunctive treatment in the treatment of MDD. An oral analogue, NRX-1074, is currently under investigation; 2) glycine antagonists, 3) mGluR modulators targeting mGluR2 and mGluR5 have demonstrated convincing preclinical results, 4) Esketamine has rapid antidepressant and antisuicidal properties, and 6) The ketamine metabolite Hydroxyketamine, an AMPA potentiator, appears to be important to the antidepressant mechanisms of ketamine and a promising drug for further development. These targets may be of substantial interest in defining future directions in drug development, as well as in developing the next generation of therapeutic agents for the treatment of mood disorders. Overall, further study of these and similar drugs may lead to a better understanding of relevant and clinically useful drug targets in the treatment of these devastating illnesses.

Innovative Tools Utilized as Biomarkers and Clinical Indicators in Autism Spectrum Disorder
Geraldine Dawson, PhD, Duke Center for Autism and Brain Development, Duke University School of Medicine

Capitalizing on advances in genetics and neuroscience, recent research has identified novel therapeutics that have the potential to modify core symptoms of Autism Spectrum Disorder (ASD), such as deficits in social communication. Success in demonstrating the efficacy of these treatments will be enhanced if clinical trials use strategies to reduce the heterogeneity of ASD, measure target engagement, and objectively quantify symptom improvement. Dr. Dawson will discuss the potential utility of several biomarkers that can be used for stratification and assessing early efficacy in ASD clinical trials, with a focus on electroencephalographic, eye-gaze tracking, and magnetic resonance iamging measures. Two ongoing efforts to validate ASD biomarkers will be described. One is a multi-site study funded by the National Institutes of Health entitled the Autism Biomarker Consortium for Clinical Trials, and the second is a recently-completed study with the Janssen Autism Knowledge Engine (JAKE™). Autism Biomarker Consortium for Clinical Trials is a longitudinal study of 200 children with ASD and 75 typically-developing children, age 4–11 years, who are being followed over 6 months with a comprehensive phenotypic, genomic, and repeated measures electroencephalogram and eye-gaze tracking biomarker assessment battery. The JAKE™ study was designed to validate a comprehensive and scalable system that utilizes biosensors and novel behavioral assessments and is feasible for use in large multi-site ASD clinical trials. It is hoped that these novel approaches to clinical trial design will facilitate the development of new and more effective treatments for ASD.

Using Neuroscience to Inform Clinical Thinking: Applications in Pediatric Anxiety
Daniel S. Pine, MD, National Institute of Mental Health, US National Institutes of Health, Bethesda, Maryland, United States

This presentation will review research in three areas. First, the presentation briefly will review key principles in translational research applications to pediatric anxiety disorders. This will delineate the way in which neuroscience concepts can be applied to clinical problems at a relatively broad level, with specific relevance to pediatric anxiety. Second, the presentation will describe the ways in which brain-behavior relationship differ in healthy children and adolescents, relative to children and adolescents with anxiety disorders. This will focus on specific aspects of attention and memory. Third, the presentation will describe the way in which this understanding of brain-behavior relationships informs understandings of developmental trajectories and novel approaches to treatment. As such, across these three levels, the presentation will describe research on pediatric anxiety disorders, as it relates to underlying brain circuitry and clinically-relevant extensions of research in animal models.

The Emerging Neurobiology of Anorexia Nervosa
B. Timothy Walsh, MD, New York State Psychiatric Institute and College of Physicians & Surgeons, Columbia University

Anorexia nervosa is an enigmatic disorder. Many individuals who develop it make a complete recovery, physically, psychologically, and behaviorally. Yet others become chronically ill, and may even die. The salient behavioral problem is a simple one: insufficient food intake. Affected individuals are not psychotic, and some have good insight into their illness, but, even so, find it very difficult to change their eating behavior. These facts, universally acknowledged, challenge our current understanding of anorexia nervosa.
 
This talk will briefly review recent studies probing the neurobiology of anorexia nervosa, and describe a newly formulated hypothesis that attempts to explain the persistence of the disorder using recent insights from cognitive neuroscience.

Harnessing Mobile and Sensor Technology to Help Patients with Diseases of the Brain and Central Nervous System
Vaibhav Narayan, MBA, PhD, Janssen Research & Development, LLC

This talk will focus on how advances in mobile computing and sensor technology may be harnessed to develop solutions that help us move from a "diagnose and treat" to a "predict and preempt" paradigm in treating diseases of the brain and central nervous system. Today, ubiquitous mobile technologies and small unobtrusive sensors make it possible to capture streaming data that report aspects of patients' physiology, behavior, and symptoms, both quantitatively and in real time. The growing content available from these devices, and the fact that these data can be passively collected and analyzed in real-time present a tremendous opportunity for early detection and monitoring of brain and CNS diseases. Measures of changes in daily activity levels, sleep, energy consumption, and social interaction patterns could have ramifications in predicting and preempting relapse in neuropsychiatric diseases such depression, bipolar disorder and schizophrenia. Neurodegenerative diseases such as Alzheimer's impact cognitive domains related to episodic memory, spatial orientation, and processing speed, all of which can be measured passively and unobtrusively.

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