Family history of alcoholism mediates the frontal response to alcoholic drink odors and alcohol in at-risk drinkers

Although a family history of alcoholism is the strongest risk factor for developing alcohol dependence, there are few studies of the association between familial alcoholism and the human brain's reward system activity. We used functional magnetic resonance imaging (fMRI) to determine how family history affects the brain's response to subjects' preferred alcoholic drink odors (AO) as compared to appetitive control odors (ApCO). Fourteen non-dependent heavy drinkers (HD) who were family history positive (FHP) participated, as did 12 HD who were family history negative (FHN). Subjects were imaged under both alcohol intoxication and placebo, using intravenous infusion and pharmacokinetic modeling to target a blood alcohol level of 50 mg%. Under placebo, HD-FHP had a larger medial frontal [AO>ApCO] effect than did HD-FHN. Alcohol intoxication dampened this response in the HD-FHP but potentiated it in the HD-FHN. This suggests that a family history of alcoholism and brain exposure to alcohol interact in heavy drinkers to differentially affect how the brain responds to alcohol cues.