The rapid advances and growing interest in neuroimaging have begun to identify a number of structural brain features that may qualify as endophenotypes for AUD [13]. Disentangling premorbid differences from the effects of alcohol on the brain is an inherent difficulty of work in this area, as it is known that even subclinical alcohol use disrupts typical neurodevelopment [85] and chronic alcohol abuse accelerates loss of white and gray matter volume [86]. Brain structure is highly heritable (e.g., frontal and language-related structures (h2 > 80%) [87] and white matter volume (h2 = 96%) [88]). Alcohol-dependent individuals have reduced volume in the right hippocampus compared to unaffected controls [89, 90]. Brain volume differences are also observed in alcohol-naïve children, adolescents, and young adults who are at high familial risk for AUD, as evidenced by reduced gray matter volumes across multiple brain regions (superior frontal, cingulate and parahippocampal gyri, amygdala, thalamus, and cerebellum) compared to matched controls at low familial risk for AUD [91]. In this same study, smaller gray matter volumes in many of these regions were associated with elevated externalizing
