Scientists receive NARSAD Distinguished Investigator Grants for mental health research

Grants Valued At $1.5 Million go to scientists pursuing innovative mental health research

The Brain & Behavior Research Foundation today announced the award of NARSAD Distinguished Investigator Grants valued at $1.5 million to 15 scientists, who are full professors or the equivalent, conducting innovative projects in diverse areas of neurobiological and behavioral research. Recipients of the $100,000, one-year grants are seeking new potential targets for understanding and treating psychiatric disorders that affect one in four people, including schizophrenia, depression, anxiety, bipolar disorder and forms of substance abuse.

Recipients of the 2014 NARSAD Distinguished Investigator Grants for basic research, new technologies and next generation therapies were selected by the Foundation's Scientific Council, which comprises 146 leading experts across disciplines in brain and behavior research, including two Nobel Prizewinners; four former directors of the NIMH; 13 members of the National Academy of Sciences; 20 chairs of Psychiatry and Neuroscience Departments at leading medical institutions; and 45 members of the Institute of Medicine.

"The Distinguished Investigator awards encourage proven scholars to stretch in different directions or take a broader view of their current work in order to ask important questions they may not be able to examine under current funding structures," says Foundation President and CEO Jeffrey Borenstein, M.D. "The Foundation's distinctive funding model supports scientists at all levels of their careers, which is critical as traditional funding has declined. In the field of mental illness, NARSAD grants serve as 'venture capital' to fund the development of the most creative new ideas."

"The awards for 2014 represent a broad and extremely exciting and important set of projects," said Jack D. Barchas, M.D, Chair and Barklie McKee Henry Professor of Psychiatry at Weill Cornell Medical College, and Psychiatrist-in-Chief at Weill Cornell Medical College, NewYork-Presbyterian Hospital and Paine Whitney Clinic, who chairs the Scientific Council's Distinguished Investigator selection committee. He noted that the committee was particularly interested in research that looked at patient populations with unique or unusual characteristics and central nervous system developments.

"The underlying fundamental neurobiology and psychobiology are beginning to come together in ways which suggest the emergence of a new integrative science for dealing with mental illness and addictive states," says Dr. Barchas, "The nature of syndromes and the multiplicity of forms of disorders have become important matters. Are there scores of causes and types of treatments? Even disease such as diabetes, once thought to be relatively clear cut in its causes and treatments, is now recognized as extremely complex. Will depression, to take just one example, be like that? We believe so."

The Recipients of the 2014 Distinguished Investigator Grants are as follows:

Basic Research:

Karen Faith Berman, M.D., National Institute of Mental Health (NIMH/NIH) (Autism)

Dr. Berman will investigate the effect of genetic variation in autism spectrum disorder by comparing copy number variation (CNV) in autism and Williams syndrome, a rare developmental disorder. Dr. Berman hopes to uncover basic information about the neurogenetic mechanisms of social behavior, cognitive disability and brain plasticity during fetal development that play a role in autism.

Gerard Sanacora, M.D., Ph.D., Yale University (Depression)

Dr.Sanacora will seek deeper understanding of the mechanisms underlying major depressive disorder by exploring the role of glial-mediated glutamate clearance in stress sensitivity. The hope is that increasing or preserving glial glutamate transporter function will reverse or attenuate the changes associated with stress commonly seen in the brains of patients with depression and provide novel targets for future pharmacological treatment development.

Angelique Bordey, Ph.D., Yale University (Schizophrenia)

Dr. Bordey hopes to gain insight into how brain circuits and networks are altered to give rise to psychiatric disorders, in particular schizophrenia, by focusing on the exchange of exosomes between neurons. The working hypothesis is that exosomes released from diseased neurons act as disease carriers that spread and amplify cellular and molecular abnormalities across developing neuronal networks.

Jane R. Taylor, Ph.D., Yale University School of Medicine, Yale University (Schizophrenia)

Dr. Taylor will create rodent models to explore the cognitive impairments of schizophrenia, which are not understood and for which effective pharmacotherapies are lacking.

Suzanne Zukin, Ph.D., Albert Einstein College of Medicine of Yeshiva University (Schizophrenia)

Dr. Zukin's overall objective is to identify mechanisms that affect N-methyi-D-aspartate receptors (NMDARs) during normal and abnormal brain development in order to understand cognitive impairments associated with schizophrenia.

Jill M. Goldstein, Ph.D., Brigham and Women's Hospital, Harvard University (Multiple Disorders)

To explore why major depressive disorder appears to increase the risk for late-life cognitive decline and Alzheimer's disease, with twice the risk for women, Dr. Goldstein will test the hypothesis that inflammation during fetal develop disrupts the hypothalamic-pituitary-adrenal (HPA) axis development. Dr. Goldstein proposes to link immune pathway disruptions transmitted in utero with sex-dependent depression and later memory circuitry deficits using data from a 50-year cohort of adults followed since gestation.

Robert D. Hawkins, Ph.D., Columbia University (Multiple Disorders)

Dr. Hawkins is studying synapse formation during long-term plasticity. Synaptic plasticity, a change in synaptic connections between neurons, is thought to underlie neural circuit formation and memory and to be disrupted in many psychiatric disorders, including schizophrenia, autism, ADHD, Rett syndrome, Alzheimer's disease and drug addiction.

Tracey J. Shors, Ph.D., Rutgers University (Multiple Disorders)

Dr. Shors's goal is to validate a novel animal model known as SCAR, which stands for Sexual Conspecific Aggressive Response, which produces persistent deficits in learning, neurogenesis and maternal behavior in pubescent female rats exposed to sexually aggressive males. Dr. Shors will use the model to identify the necessary and sufficient brain processes and mechanisms that induce negative, long-lasting consequences on affect and cognition in women in response to early sexual trauma.

Claes Wahlestedt, M.D., Ph.D., University of Miami (Multiple Disorders)

Dr. Wahlestedt will investigate the role of microRNA, miR -134, in the epigenetic dysregulation in schizophrenia and depression. He will also expand his focus from microRNAs to epigenetic enzymes as possible targets for pharmaceutical treatment of schizophrenia and depression.

Yi E. Sun, Ph.D. University of California, Los Angeles

Dr. Sun is studying the differing roles of a microRNA, miR-9, in regulating fear-related learning and memory during development and in adulthood. Having confirmed a developmental role of miR-9, Dr. Sun now wants to investigate the molecular mechanisms underlying adult-onset miR- 9 activity in the regulation of fear memory.

New Technologies:

Henry A. Lester, Ph.D. California Institute of Technology (Addiction)

To better understand nicotine addiction, Dr. Lester will lead a proof-of-principle project of a new tool he and colleagues have developed for determining nicotine concentration in subcellular compartments in neurons.

Next Generation Therapies

David Eldon Clapham, M.D., Ph.D., Harvard Medical School, Harvard University (Anxiety)

Dr. Clapham is investigating the role of TRPC channels as novel regulators of fear and anxiety and as potential therapeutic targets. He hopes to improve knowledge of the neuronal microcircuits they affect and how genes influence these circuits in normal behavior and in anxiety-related disorders.

Lee Stuart Cohen, M.D., Massachusetts General Hospital, Harvard University (Depression)

Dr. Cohen will investigate the neurobehavioral effects of fetal exposure to maternal use of the widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants. The outcomes will help to inform the care of reproductive-age women treated with psychiatric medications and the relative subsequent risks to their children of using these agents during pregnancy.

Lisa M. Monteggia, Ph.D., University of Texas Southwestern Medical Center at Dallas (Depression)

Dr. Monteggia wants to learn how and where in the brain the antidepressant ketamine works. While remarkably faster and more effective for more patients than currently available antidepressants, ketamine's use has been limited by problematic side effect. Working with mouse models, Dr. Monteggia will build on her findings of ketamine action in the hippocampus, a brain region implicated in the pathophysiology and treatment of depression.

Paul F. Worley, M.D., Johns Hopkins University (Schizophrenia)

Dr. Worley is investigating a possible new treatment target for schizophrenia by looking at a gene called Arc that is significantly linked to schizophrenia and is implicated in other diseases of cognition.

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