MECHANISM OF ETHNIC DIFFERENCES IN PSYCHOTROPHIC RESPONSES

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To compare the response and explore potential reasons for differences in response to psychotropic medication in different ethnic groups. The factors hypothesized in determining response are: inherited differences in drug metabolizing liver enzyme systems, protein binding, and dietary influences. To evaluate subjects from Puerto Rican, Native American, African-American, Asian, Caucasian and Hispanic backgrounds with extensive physical and laboratory examinations. The investigation will be composed of two parts: part 1 will be devoted to pharmacogenetics and protein binding and will start in year one and continue for the duration of the five year grant, while part II will address dietary influences and start in the third year. Results will lead to the development of a panel of pharmacogenetic tools that can be applied in clinical settings for predicting the pharmacokinetics and effects of many psychotropics as well as a better understanding of environment and diets in the activity of these drug metabolizing enzymes. Preliminary results indicate mutations of CYP2D6 as highest in Caucasians and lowest in Asians. Data on African and Mexican-Americans, however, suggest significant intermixing of ancestral groups for 2D6.