Project Summary

John S. March, M.D. (Distinguished Investigator 2006) of Duke University, is investigating genetic mutations potentially involved in behavioral activation or suicide-related behavior in youth exposed to the antidepressant medications known as serotonin reuptake inhibitors (SSRIs). Behavioral activation involves aspects of mania, disinhibition, and motor restlessness and is difficult to characterize; however, incidence is probably 2 to 10percent of children and adolescents treated with SSRIs. Adverse drug reactions (ADRs) to SSRIs are a common problem. Emerging evidence suggest that ADRs are influenced by polymorphic genes. Dr. March will seek to establish a genetic susceptibility database by creating a DNA repository of patients with drug-induced behavioral activation or suicide-related behavior, identify genetic mutations responsible for the development of behavioral activation or suicide-related behavior using a candidate gene approach, and create a DNA repository of closely matched SSRI-tolerant controls. Ultimately, Dr. March believes that individuals susceptible to ADRs associated with genetic polymorphisms can be determined by advances in pharmacogenomics, though, to date, specific mutations responsible for ADRs related to marketed drugs are not yet defined

Program Area: MOOD DISORDERS

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