Alcohol and HIV risk: Genetic and endophenotype approaches

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Alcohol use Is a significant behavioral cofactor for HIV transmission. The association of alcohol with sexual risk behavior appears especially strong among high-risk adolescents, including adjudicated adolescents, who are at particular risk due to high rates of alcohol use and comorbid psychiatric disorders. Theoretical models of sexual risk behavior rely almost exclusively on social-cognitive perspectives. Basic knowledge about biological influences on HIV risk behavior, including alcohol-related risk taking, is virtually non-existent. Externalizing behaviors in adolescence and young adulthood show a common genetic diathesis, suggesting common biological and/or temperamental influences. In particular, shared genetic risk for a spectrum of externalizing behaviors, including sexual behavior, is attributed to a highly heritable factor reflecting behavioral disinhibition. Recent research has linked specific genetic variants to cognitive, behavioral and neurobiological phenotypes associated with behavioral disinhibition and externalizing disorders. Given the importance of the mesolimbic dopamine system in reward-related behavior and risk-based decision-making, genes with implications for dopaminergic function are high-priority candidates. The goal of the proposed research is to evaluate genetic factors that may a) predict common risk for alcohol use, sexual risk behavior and other externalizing behaviors, and/or b) moderate the association of alcohol use and HIV risk behavior. This research will take place in the context of a prospective investigation of genetic and neurobiological correlates of alcohol and HIV risk-taking among adjudicated adolescents (R01AA017390-01). Analyses will examine genetic influences on alcohol use, HIV risk behaviors and externalizing behaviors using impulsivity/disinhibition as a plausible endophenotype. Specific hypotheses concerning the moderating effect of the DRD4 VNTR polymorphism on alcohol-related sexual risk behavior will be evaluated. This project, which responds to the need for integrative and translational methods in studies of alcohol and HiV risk, will contribute basic information about genetic factors and related behavioral characteristics that may place some individuals at elevated risk for HIV via the propensity for externalizing behaviors, including alcohol use.