Sex Differences in the Effect of Nucleus Accumbens Volume on Adolescent Drinking: The Mediating Role of Sensation Seeking in the NCANDA Sample

Objective: In adolescence, sensation seeking is associated with earlier onset of alcohol use, which is a risk factor for a variety of negative consequences later in life. Individual differences in sensation seeking are related to brain function in the nucleus accumbens (NAcc), a brain region that undergoes considerable structural development during adolescence. Therefore, the goal of this study was to determine whether NAcc volume in alcohol-naive adolescents was associated with future sensation seeking and alcohol use and whether these associations differed by sex. Method: High-resolution magnetic resonance imaging was used to measure NAcc volume at baseline in 514 alcohol-naive adolescents (50.2% female) from the National Consortium on Alcohol & Neurodevelopment in Adolescence study. Direct effects of NAcc volume on adolescent drinking 2 years after baseline, and indirect effects mediated through sensation seeking 1 year after baseline, were assessed. Results: An indirect effect of NAcc volume on subsequent drinking through sensation seeking was significant for males, but not females. This effect was driven by a positive association between NAcc volume and sensation seeking observed in male, but not female, participants. A direct effect of NAcc volume on subsequent alcohol use was detected in females, but not males. In females, no association between NAcc volume and sensation seeking was detected, but NAcc volume was positively associated with future alcohol use. Conclusions: These findings suggest that delayed structural maturation of the NAcc may be a risk factor for alcohol use in adolescence; however, the mechanism by which the structure of the NAcc confers risk differs by sex.