Limitations notwithstanding, our study provides convergent evidence that smaller GMV in the insula and DLPFC associated with alcohol use may represent a genetically conferred liability that promotes early alcohol use. While early alcohol use may in turn lead to accelerated volume loss within these and other regions, these findings challenge predominant interpretations that smaller brain volumes tied to alcohol use emerge primarily from the atrophy-inducing effects of alcohol. As larger prospective samples are acquired (e.g., via the Adolescent Brain Cognitive Development study) (79), it will be interesting to examine the interplay of genetic risk and substance use on the trajectories of brain development.
