June 3, 2005

Investigators nab schizophrenia research grants

Investigators nab schizophrenia research grants

The National Alliance for Research on Schizophrenia and Depression (NARSAD) has awarded grants for neurobiological research to seven investigators at Vanderbilt University Medical Center.

Randy D. Blakely, Ph.D., has received a one-year, $100,000 Distinguished Investigator Award for a novel approach to explore antidepressant action in vivo.

Six other scientists have received Young Investigator Awards, which provide up to $30,000 per year for one or two years.

NARSAD is the largest donor-supported organization in the world devoted exclusively to supporting scientific research on brain and behavior disorders, according to its Web site. Since 1987, NARSAD has awarded $175.7 million in research grants to 2,067 scientists throughout the world.

Blakely and colleagues study neurotransmitter transporters, proteins that act like “molecular vacuum cleaners” to clear neurotransmitters from the synaptic space between nerve cells. Blakely was the first to isolate genes for the transporters that clear norepinephrine and serotonin. Drugs with important clinical or addictive properties, including antidepressants, cocaine, and amphetamines, interfere with the function of these transporter molecules.

Blakely's team, including postdoctoral fellow Keith Henry, Ph.D., and graduate student Julie Field, has identified mutations in the serotonin transporter that selectively disable recognition of a number of antidepressants, like Prozac and Lexapro, but leave serotonin recognition unperturbed. The mutations also diminish cocaine recognition.

The investigators plan to generate mice with this selectively disabled serotonin transporter in the place of the normal serotonin transporter. Such mice represent a novel model for investigating antidepressant and psychostimulant action and discovering changes in gene expression that depend on serotonin signaling, said Blakely, Allan D. Bass Professor of Pharmacology and director of the Center for Molecular Neuroscience,.

Investigators receiving 2005 Young Investigator Awards are:

• Stefania Bonaccorso, M.D., clinical fellow in Psychiatry — Bonaccorso is working with Herbert Y. Meltzer, M.D., director of the Division of Psychopharmacology, to assess divalproic acid as an adjunct therapy with antipsychotic drugs in the treatment of schizophrenia and schizoaffective disorder.

• Yuejin Chen, M.D., Ph.D., assistant clinical professor of Psychiatry — Atypical antipsychotic drugs and anticonvulsant mood stabilizers are often combined to treat schizophrenia and bipolar disorder, with a risk of metabolic side effects including insulin resistance. Chen and Meltzer will identify offending combinations and develop guidelines for safer use of combination treatment.

• Mei Huang, Ph.D., research fellow in Psychiatry — Huang and Meltzer are studying the mechanism of action of antipsychotic drugs used to treat schizophrenia and depression. Using microdialysis, Huang will evaluate the role of two types of serotonin receptors in antipsychotic drug-induced release of dopamine and acetylcholine, which is believed to contribute to drug efficacy in schizophrenia treatment.

• Harish C. Prasad, M.D., Ph.D., postdoctoral research fellow in Pharmacology — Prasad is working with Blakely to study the functional genomics of the human serotonin transporter in mood disorders. He will assess how variations in the transporter gene sequence affect the protein's function, and he will look for evidence that gene variants are present in patients with major depression.

• Tianlai Tang, M.D., Ph.D., assistant clinical professor of Psychiatry — Tang and Meltzer are evaluating the usefulness of Holter monitor recording versus routine EKG in determining the risk of arrhythmia in patients taking specific antipsychotic drugs. They hope the study will help clarify why the risk of sudden death is increased in patients with schizophrenia.

• Chong-Bin Zhu, M.D., Ph.D., research assistant professor of Pharmacology — Recent studies suggest that compromised immune function and inflammatory mediators play a role in triggering, modulating or sustaining psychiatric diseases. Zhu, mentored by Blakely and William A. Hewlett, M.D., Ph.D., associate professor of Psychiatry, will examine how inflammatory mediators modulate serotonin transporter function.