Excessive alcohol use is an escalating international health problem that accounts for over 5% of global deaths and disease burden (1). Alcohol use and use disorders have been reliably associated with magnetic resonance imaging (MRI)-derived brain structure phenotypes, particularly among regions and pathways that feature prominently in executive function, incentive salience, and negative emotionality (2,3). For instance, the largest mega-analysis of Alcohol Use Disorder in adults (n cases = 898, n controls = 292) found lower volume and cortical thickness of subcortical (n=11; e.g., hippocampus, amygdala, nucleus accumbens, putamen) and cortical regions (n=27; e.g., insula, superior frontal gyrus; orbitofrontal cortex), respectively (2). Consistent with evidence from non-human animal models, it is widely speculated that these structural reductions arise as a consequence of chronic alcohol exposure and contribute to the development of alcohol-related comorbidities (e.g., risk taking, Alzheimer’s Disease) (4,5). However, emerging data challenging this common interpretation suggest that these brain structure correlates may, at least partially, reflect genetically conferred predisposing risk factors for alcohol involvement (6,7). For example, studies of substance naïve children of parents with AUD have observed similar
