About 5% of adult women in the US develop alcohol dependence. Findings from clinical populations and alcohol use surveys report more women than men with family histories of alcoholism. This application requests continued support for research aimed at identifying biological and behavioral markers that could more precisely predict risk of alcoholic and control men, or men with positive (FHP) versus negative (FHN) family histories of alcoholism. To facilitate analysis of possible gender differences, we have designed studies of women that parallel measures examined n men in other laboratories. Earlier and ongoing studies of physiological, behavioral, and subjective marker that we have conducted found differential alcohol sensitivities to alcohol in FHP and FHN women. We now propose to further refine and extend ongoing research to examine ACTH level, as well as cortisol and prolactin , following alcohol or placebo, and to perform in vitro perturbation assays of platelet monoamine oxidase (MAO) and adenylate cyclase (AC) activities. STUDY 1 will examine acute 0.56 g/kg alcohol versus placebo effects on ACTH, cortisol, and prolactin levels, subjective effects, and task performance in healthy woman ages 21 to 28 who consume about 2 alcohol drinks twice a week. Subjects will be screened for family history of alcoholism in biological parents and full siblings. Woman with alcoholic fathers will be classified as FHP, and women with no family history of alcoholism as FHN. Subjects will be matched for age, alcohol use, height- wight ratio, and education. Thirty FHP and 30 FHN women will be studied in a group design wherein 15 FHP and 15 FHN women receive alcohol and 15 FHP and 15 FHN women received placebo. Studies will occur during the follicular menstrual cycle phase to minimize hormonal variability. In vitro perturbation of platelet MAO and AC activities were first reported as possible alcoholism markers in men. Our pilot data confirmed the potential importance of these putative risk marks for development of alcoholism by extending investigation to FHP and FHN women. STUDY 2 will add assays of in vitro perturbation of platelet MAO and AC activities to STUDY 1 measures and also will assess possible differential MAO or AC activities in alcoholic FHP and FHN women. It is important to examine possible gender differences in putative risk marker of alcoholism because these indices may have implications for understanding pathogenesis as well as for developing prevention strategies. Studies that are proposed in this application will provide a more comprehensive end integrated view of biological, behavioral, and subjective risk factors that could illuminate possible mechanisms involved in predisposition to alcohol abuse. If consistent and reliable behavioral and biological changes differentiate FHP from FHN women, a multivariate profile could yield more powerful indication so potential risk than any single variable.
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