Project Summary

Herbert Meltzer, M.D. (Distinguished Investigator 2007) of Vanderbilt University, aims to identify candidate genes associated with schizophrenia that determine the genetic component of specific domains of cognition, e.g. working memory, and psychopathology, e.g. hallucinations, at an initial assessment and longitudinally, including a 10 year to15 year follow-up period, in patients with schizophrenia. He further plans to apply multifactor-dimensionality reduction to improve the identification of the polymorphism combinations associated with cognitive impairment and psychopathology. Additionally, he proposes to determine the ability of candidate genes to predict response to antipsychotic drug (APD) treatment; and to determine the functional effects of the serl23lcys SNP of the 5-HT2C receptor by producing a transgenic mouse which overexpresses a possibly functional mutant form of the 2C receptor and comparing its phenotype with the wild type by determining cortical and limbic dopamine and acetylcholine efflux using microdialysis. This work should greatly contribute to the understanding of the genetics of cognition and psychosis with implications for understanding the relationships between cognition and psychopathology.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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