We propose to identify consistent predictors of reactivity to alcohol challenge based on (a) family history of alcohol abuse, (b) individual behavioral, personality, and cognitive risk factors, and (c) recent drinking history. We will study three samples of young adults: (1) Subjects selected for differential risk based on differences in family history of alcohol abuse; (2) Discordant sibling pairs selected for differential risk, so that one sibling has the heightened profile of behavioral, personality, and cognitive risk factors reported for subjects with a family history of alcohol abuse, while the other sibling shows a low risk profile, similar to subjects with no family history of alcohol abuse; and (3) Monozygotic (MZ) twins assessed for the same risk factors as the first two samples. Exploiting the naturalistic weekend drinking patterns of young adults, all subjects will be tested in alcohol challenge once after several days of drinking, and once after several days abstinence, allowing evaluation of the effects of recent drinking and interactions of those effects with risk status. We will extend previous work on disinhibition as a risk factor for alcohol problems by conducting multi-method assessments of disinhibitory characteristics, and we will evaluate the association of those characteristics with family risk and reactivity to alcohol challenge. The MZ twins will be tested both in our oral dosing protocol and in the clamping protocol proposed by our colleagues at IUSM, providing an estimate of consistency of individual differences in reactivity across protocols, and an upper bound estimate of the heritability of individual differences in risk factors and in the alcohol response patterns assessed in each site. In combination, the three sampling strategies and the within-subject evaluation of recent drinking effects provide an efficient program for evaluating putative markers of genetic risk.
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