Second, we found that PAU-PRS are associated with thicker supramarginal gyrus cortex. Greater supramarginal gyrus thickness has been found in substance-naïve children of alcohol dependent individuals (8); however, the supramarginal gyrus is thinner among those with alcohol dependence (2). It is possible that some brain structure correlates of alcohol involvement may be developmentally dependent. Indeed, throughout childhood and adolescence neuronal pruning appears to support long term planning, working memory performance, language, and attention (34). It has been postulated that greater indices of gray matter among those at familial risk for alcohol problems may reflect a developmental delay in neural pruning that places adolescents at risk for substance use, which, in turn, accelerates neuronal pruning in later development (35). Given that the supramarginal gyrus is thicker among those at elevated risk for problematic alcohol use and this region supports cognition and language (36), this is plausible. However, supramarginal gyrus cortical thickness was not significantly correlated with cognition (Supplemental Table 4).
