July 27, 2007

Grants bolster research into psychiatric disorders

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Herbert Meltzer, M.D.

Grants bolster research into psychiatric disorders

NARSAD: The Mental Health Research Association recently awarded grants for neurobiological research into psychiatric disorders to four researchers at Vanderbilt University Medical Center.

Herbert Meltzer, M.D., professor of Psychiatry and Pharmacology and director of the Division of Psychopharmacology, has been selected to receive a Distinguished Investigator Award, which supports highly significant research by established scientists. The grant will provide a one-year grant of $100,000 to advance Meltzer's work in identifying candidate genes associated with schizophrenia.

He is focusing on candidate genes for specific aspects of the disorder. He will use the award to look at specific domains of cognition, such as working memory, and of psychopathology, such as hallucinations. Meltzer plans to study these behavioral processes over time to identify gene differences associated with these specific components and determine how they relate to one another, paying particular attention to genes involved in serotonin and dopamine pathways.

With the assistance of Ron Emeson, Ph.D., in Pharmacology, Meltzer's NARSAD award will also enable the creation of a transgenic mouse which will overexpress one of the key mutations which may convey vulnerability to schizophrenia. These methods can then be applied to examining the response to medications, which could result in genetic tests to improve therapeutics.

In addition, three other Vanderbilt scientists have received NARSAD's 2007 Young Investigator Award, which was established to help promising new investigators — post-doctoral fellows, advanced-standing medical residents and assistant professors — to generate pilot data necessary for larger grants. Each of the scientists will receive $60,000 from NARSAD for the next two years to advance specific research projects.

Alexandre Bonnin, Ph.D., a research fellow in Pharmacology, will study serotonin, a neurotransmitter thought to regulate many aspects of brain development. He will attempt to define serotonin's role in brain circuit formation using a mouse model in which serotonin levels are dramatically decreased in the embryonic forebrain. He will also investigate the possibility that serotonin could influence the formation of its own circuit at early stages of development.

Ana Carneiro, Ph.D., instructor in Pharmacology, plans to study two proteins present both in blood platelets and in neurons — one that activates the platelets to form blood clots; the other to control levels of serotonin both in the blood and in the brain, and which is also the main target of antidepressant drugs. Carneiro has discovered that when these two proteins bind together, the activation of one protein is directly transmitted to the other. Carneiro's study suggests a common molecular link in the pathophysiology of depression and heart attacks that could explain the increased risks observed in the population.

Mei Huang, Ph.D., research fellow in Psychiatry, will explore the role of certain cell receptors that may be involved in regulating the release of the neurotransmitter dopamine in the medial prefrontal cortex area of the brain. This research, using so-called knockout mice in which genes have been inactivated, is aimed at elucidating receptor mechanisms that may help to explain how atypical antipsychotic drugs such as clozapine, olanzapine and risperidone affect dopamine transmission, and why some of these atypical antipsychotics are clinically superior to other antipsychotic drugs.