Individuals family-history positive (FHP) for alcoholism have increased risk for the disorder, which may be mediated by intermediate behavioral traits such as impulsivity. Given the sex differences in the risk for and clinical presentation of addictive disorders, risk for addiction may be differentially mediated by impulsivity within FHP males and females. FHP (N ¼ 28) and family-history negative (FHN, N ¼ 31) healthy, non-substance-abusing adults completed an fMRI Go/No-Go task and were assessed on impulsivity and alcohol use. Effects of family history and sex were investigated as were associations between neural correlates of impulse control and out-ofscanner measures of impulsivity and alcohol use. FHP individuals showed greater activation in the left anterior insula and inferior frontal gyrus during successful inhibitions, an effect that was driven primarily by FHP males. Higher self-reported impulsivity and behavioral discounting impulsivity, but not alcohol use measures, were associated with greater BOLD signal in the region that differentiated the FHP and FHN groups. Impulsivity factors were associated with alcohol use measures across the FHP and FHN groups. These findings are consistent with increased risk for addiction among FHP individuals being conferred through disrupted function within neural systems important for impulse control. Keywords: impulsivity; family history of alcoholism; insula; inferior frontal gyrus (IFG); addiction; sex differences.
INTRODUCTIONAlcohol use disorders (AUDs) are prevalent and associated with detrimental health and societal outcomes (Li, 2008). Individuals with a family history of alcoholism (familyhistory positive (FHP)) have increased risk for alcoholism driven by genetic and environmental factors (Lieb et al, 2002;Slutske et al, 2002). Healthy FHPs model addiction vulnerability without confounding effects of excess alcohol on cognition and brain function.Increased AUD risk among FHPs may be conferred via heritable impulsive tendencies (Dick et al, 2010;Tessner and Hill, 2010). Impulsivity is a multi-factorial construct, where distinct sub-components appear to have differential neural bases and relationships with addiction (de Wit, 2009;Lejuez et al, 2010;Rogers et al, 2010). Aspects of impulsivity may both predispose to and be exacerbated by addictive behaviors. Impulsivity predicts development of AUDs; is higher in FHPs with more alcohol-dependent relatives (ie higher family-history load); and partially mediates the relationship between FHP and alcohol and substance use disorder (for review, see de Wit, 2009;Dick et al, 2010;Lejuez et al, 2010;Verdejo-Garcia et al, 2008). Other less well-studied impulsivity-related constructs (eg, sensationseeking, risk-taking, compulsivity, behavioural activation/ inhibition, reward/punishment sensitivity) have been related to addiction vulnerability, and addictions therefore warrant consideration (eg, Meda et al, 2009).Sex differences are important to consider as they are observable for rates, clinical presentation, and health cons...