Along similar lines and consistent with the propositions put forth by the research domain criteria (RDoC) initiative,55 it is possible that the neural risk phenotypes we identified may predispose to two distinct cross-disorder vulnerabilities: one associated with impulse control and behavioral disinhibition, and one associated with negative emotion dysregulation, broadly defined, rather than simply two distinct pathways of risk for “pure” AUD. In further support of this notion and consistent with prior literature,56, 57 more than one third of the participants meeting criteria for AUD in the current sample had a comorbid disorder (Supplementary Table 2). While the current study is underpowered to detect contributions of each neural risk phenotype to specific diagnostic comorbidities, this notion can be tested in cohorts enriched for other psychiatric disorders and/or followed longitudinally to assess lifetime comorbidity.
