NEW YORK CITY (Dec. 8, 2015)-- The Brain & Behavior Research Foundation today announced the award of its 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, bipolar disorder, substance abuse, PTSD and autism spectrum disorders.
Recipients of the 2015 Distinguished Investigator Grants were selected by the Foundation's Scientific Council, which comprises 165 leading experts across disciplines in brain and behavior research, including two Nobel laureates; four former directors of the NIMH; 13 members of the National Academy of Sciences; 23 chairs of Psychiatry and Neuroscience Departments at leading medical institutions; and 52 members of the Institute of Medicine.
"The Distinguished Investigator awards encourage established scientists to explore new areas of neurobiological or behavioral research, or broaden their current research in ways that may not be possible under current funding structures," says Foundation President and CEO Jeffrey Borenstein, M.D. "These grants inspire creative approaches to understanding and treating psychiatric disorders."
"We received a large number of outstanding proposals. Some deal with a specific research problem in one area of mental illness; many are relevant for a number of illnesses; some involve basic research that will serve as the basis of clinical or translational research; and others start from a translational or clinical foundation. We are able to see the growth of the field and the manifestations of the enhanced power of research related to mental illness that have come about with the remarkable support of the Brain & Behavior Research Foundation," 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.
The Recipients of the 2015 Distinguished Investigator Grants are as follows:
Yavin Shaham, Ph.D., of the National Institute on Drug Abuse has created a rat model to investigate the mechanisms underlying voluntary abstinence from methamphetamines following addiction. Past research suggests that both humans and rats experience stronger methamphetamine cravings the longer they choose to abstain from the drug. In this study, Dr. Shaham's team will test how those increased cravings are driven by particular connections within the brain. Those connections emanate from part of the brain structures called the insula, which contribute to diverse functions from survival instincts to self-awareness, and are traced to the central part of the amygdala, the brain's emotion center. Better understanding of this circuit's impact on drug cravings, the team hopes, will improve approaches to preventing relapse among methamphetamine users.
Autism Spectrum Disorder
Daniel H. Geschwind, M.D., Ph.D., of the University of California, Los Angeles, seeks to understand the genetic basis of social and communication deficits in autism spectrum disorders. Some of these deficits can be reduced in animal models with infusions of the hormone oxytocin into the nervous system, which promotes context-dependent social behaviors. Dr. Geschwind's team will explore the genetic and molecular mechanisms driving oxytocin's effects in autism. To do so, they will study a gene expressed in oxytocin-producing neurons that encodes a chemical called Cntnap2 (for contactin-associated protein-like 2). The team will test whether the Cntnap2 gene contributes to social deficits in autism by regulating the structure of, and signaling from, oxytocin-producing neurons.
Nahum Sonenberg, Ph.D., of McGill University, will explore the activity of a protein that helps regulate gene expression, and specifically the process by which other proteins are generated, in many parts of the brain, with implications for treating autism spectrum disorder. The protein, called e-IF4E, has already been linked to autism-like deficits in animal models. Using human cells, Dr. Sonenberg's team will create different mutations affecting e-IF4E. They will then track which genes show altered expression as a result of the mutations. Since e-IF4E-controlled gene expression is already FDA-approved as a target for drug compounds, this work aims to bring researchers one step closer to exploiting e-IF4E to treat disorders on the autism spectrum.
Alan Stewart Brown, M.D., M.P.H., of Columbia University, hopes to more clearly identify which prenatal risk factors can increase a child's likelihood of developing bipolar disorder (BD). His work will focus on a cohort of 19,000 individuals born between 1959 and 1967 whose data was used to find prenatal risks for schizophrenia. Building on those findings, Dr. Brown and colleagues will investigate the effects of a mother's immune system, smoking habits and levels of thyroid hormone on children's later development of bipolar disorder. They will also study how these effects differ by sex and family history of psychiatric disorders. The findings may help inform public health interventions that improve prenatal care to reduce the risk of bipolar disorder.
Michel Barrot, Ph.D., of the University Pierre & Marie Curie, will investigate the imprint of depression on part of the brain crucial for the dopamine system. Dopamine, a chemical in the brain, plays a role in a range of neurological and psychiatric disorders. The dopamine-rich region Dr. Barrot will study is the tail of the ventral tegmental area, or the tVTA. Looking at a rat population, Dr. Barrot's team will try to identify genes with high rates of expression in the tVTA, as possible drug targets for regulating dopamine activity. Then, they will induce depression in rats to examine what the disorder looks like in the tVTA. By examining these aspects of the tVTA, the team hopes to broaden our understanding of the region's role in mood and other disorders.
Catherine G. Dulac, Ph.D., of Harvard University, will explore how different patterns of connections in the brain contribute to behaviors that define postpartum depression. Affecting about 10 percent of mothers and five percent of fathers in the U.S., postpartum depression describes prolonged emotional disruptions in parents after childbirth that can interfere with parent-child bonding. Using mouse models that parallel the biology and behavior of human parenting, Dr. Dulac's team will study connections to parenting-associated brains cells that may mediate postpartum depression. These cells are in the medial preoptic area of the hormone-producing hypothalamus. By examining these cells' neural connections, gene expression, and effects on parental behavior, the team hopes to shed light on the pathology of postpartum depression and identify possible chemical targets for treatment.
Jeffrey H. Meyer, M.D., Ph.D., FRCP(C), of the University of Toronto, hopes to shed light on periods of major depressive disorder that have been linked to abnormalities in the immune system. Some people do not get relief from depression while taking commonly prescribed SSRI-class antidepressant medication like Prozac. Dr. Meyer and colleagues recently found that in certain brain regions of some treatment-resistant patients, there are signs of increased inflammation, which reflects immune system activity. Continuing this work, Dr. Meyer's team will give such patients an anti-inflammatory drug. The team expects that among these patients, high levels of inflammation in the brain will predict strong relief from depression symptoms in response to the drug. Confirming this prediction would advance attempts to personalize depression treatment by targeting immune response in certain patients who do not respond well to current antidepressant options.
Bernice Ann Pescosolido, Ph.D., of Indiana University, will repeat and reinvent the largest U.S. survey examining persistent stigma toward mental illness. Past surveys of attitudes toward mental illness have found that many Americans do harbor prejudices about mental illness, ironically, even as more people accept neurobiological explanations for the most prevalent disorders. Dr. Pescosolido will examine whether that trend has changed in the past decade and will expand the research to other factors, including what it is like to experience mental illness-based discrimination and respondents' amount of contact with mental health diagnoses. With this research, her team aims to help reduce the health burden of stigma, which has negative effects on important recovery factors ranging from self-esteem to willingness to seek help.
Post-Traumatic Stress Disorder
Ismene L. Petrakis, M.D., of Yale University, hopes to lay the groundwork for the pharmacological treatment of overlapping post-traumatic stress disorder (PTSD) and alcohol abuse disorder. Although it is common for people to suffer from both conditions, current pharmacological treatments only target one or the other. With this study, Dr. Petrakis will investigate the hormone progesterone as a treatment option. Best known for its role in the female reproductive cycle, progesterone can also promote healthy brain activity. It has been shown to reduce alcohol withdrawal symptoms and soften physiological responses to mental stress. Among people diagnosed with both PTSD and alcohol abuse disorder, Dr. Petrakis' team will test progesterone's effects on alcohol consumption, stress responses to trauma, mood, cognition and motor coordination (while controlling for women's internal progesterone levels).
Moses V. Chao, Ph.D., of New York University, will study proteins in the brain that have previously been associated with aggressive behavior in schizophrenia. In particular, his team will expand on their previous work examining genes that encode proteins called neurotrophins. Neurotrophins support the development and function of brain cells. Dr. Chao's team hopes to identify rare mutations in neurotrophin-encoding genes linked to aggression in schizophrenia, and explore how those mutations affect signaling between brain cells. They hope to shed light on the pathology underlying aggression, which is significantly more common among people with schizophrenia and other conditions that involve distorted experiences of reality.
Paul J. Kenny, Ph.D., of the Icahn School of Medicine at Mount Sinai, will study genetic mechanisms that may give rise to behavioral deficits in schizophrenia. Specifically he will study microRNAs, or miRNAs. These brief messages copied from genes do not, like much longer RNA molecules, contain the code for manufacturing proteins. Rather, they appear to play regulatory roles. Some miRNAs are thought to help regulate structure, function and plasticity of neurons in the brain. One particular miRNA, miR-206, has been linked in schizophrenia to low amounts of the brain chemical GABA -- crucial for tamping down, and thus helping to control, communication activity among neurons. It has also been linked to symptoms of psychosis, or distorted perceptions of reality. Studying a mouse population, Dr. Kenny's team will disrupt miR-206 in certain brain cells known as interneurons, which play key modulating roles in communication networks. The team expects these disruptions to create schizophrenia-like behavioral deficits in the mice, shedding light on the miRNA's role in the disorder.
Anthony John Koleske, Ph.D., of Yale University, seeks to uncover potential drug targets to reverse the loss of connections between brain cells seen in schizophrenia. These connection deficits appear in the form of reduced dendrite structures, the branching thread-like filaments that connect neurons. Reduced dendrite structures are believed to be associated with disruptions in perception, cognition, emotional expression and motor skills among people with schizophrenia. One type of protein that may contribute to dendritic deficits is the Trio family. Dr. Koleske plans to expand his past work on Trio proteins by studying the proteins--and genes that encode them -- in greater detail. The findings, he hopes, will point toward Trio as a promising target for new schizophrenia drugs.
Edwin S. Levitan, Ph.D., of the University of Pittsburgh, will explore the precise effects of antipsychotic drugs on transmission of the brain chemical dopamine. Often used to treat schizophrenia and bipolar disorder, antipsychotics work by blocking activity at docking ports for dopamine located on the surface of nerve cells. These drugs can also enter the structures within neurons, called vesicles, that store and release dopamine. Dr. Levitan and colleagues will investigate how the buildup and release of dopamine in vesicles alters the effects of antipsychotic drugs when those drugs are also released from vesicles. Their findings may influence the design of antipsychotics and other drugs whose ingredients can get trapped in brain chemical storage sites.
Jonathan S. Mill, Ph.D., of the University of Exeter, will continue to investigate genetic patterns that build a foundation for schizophrenia. Known to have a strong genetic component, schizophrenia also has been tied to epigenetic variation -- chemical groups attaching to genes that affect gene activity. People with schizophrenia have shown unique epigenetic markers within genes that direct brain development in the fetal stage. In this study, Dr. Mill plans to study a specific epigenetic modification and how that modification changes during fetal development. This work aims to sharpen our picture of the neurodevelopment trajectory underlying schizophrenia.
David L. Sulzer, Ph.D., of Columbia University, will study brain chemicals linked to schizophrenia at the molecular level, aiming for a better understanding of the chemical processes driving the illness. Antipsychotic medications commonly used to treat schizophrenia target docking ports for the chemical dopamine, which can in turn promote the production of the chemical norepinephrine. Looking at mice, Dr. Sulzer will examine the release of dopamine and norepinephrine in response to the drug amphetamine. Amphetamine has previously been used to identify abnormalities in the dopamine systems of people with schizophrenia. His team will also look at dopamine and norepinephrine release during working memory tasks, which are impaired in schizophrenia. They hope to use this work to identify genetic factors and communication points in the brain that alter dopamine release in schizophrenia.
To learn more about the Distinguished Investigator grantees, visit: https://bbrfoundation.org/2015-narsad-distinguished-investigator-grantees
About the Brain & Behavior Research Foundation:
The Brain & Behavior Research Foundation is committed to alleviating the suffering of mental illness by awarding grants that will lead to advances and breakthroughs in scientific research. The Foundation funds the most innovative ideas in neuroscience and psychiatry to better understand the causes and develop new ways to treat brain and behavior disorders. These disorders include depression, bipolar disorder, schizophrenia, autism, attention-deficit hyperactivity disorder, anxiety, borderline personality disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Since 1987, the Foundation has awarded more than $342 million to fund more than 5,000 grants to more than 4,000 leading scientists around the world. This has led to over $3 billion in additional funding for these scientists. The Foundation is also dedicated to educating the public about mental health and the importance of research including the impact that new discoveries have on improving the lives of those with mental illness, which will ultimately enable people to live full, happy and productive lives. For more information, visit http://www.bbrfoundation.org.