Independent Effects of Alcohol Use Disorder and Early Life Stress on Negative Emotionality

Background Early life stress (ELS) is a risk factor for alcohol use disorder (AUD) and may contribute to heterogeneity in clinical presentation. Using the Addictions Neuroclinical Assessment (ANA) framework, this study examined (1) associations between ELS and ANA domains within AUD; and (2) effects of AUD and ELS on ANA domains using a case–control design. Methods Adults with AUD (n=100) and controls (n=95) completed the Adverse Childhood Experiences (ACE) Questionnaire and phenotypic battery. Participants were classified as no-ELS, moderate-ELS, or high-ELS. Within AUD, ELS group differences in ANA domains were tested with univariate ANOVA. For case–control analyses, ELS and AUD effects were examined using 2 (AUD, control) × 3 (ELS groups) ANOVAs. Linear regression examined associations between continuous ACE scores and ANA domains. Results In AUD, the high-ELS group exhibited elevated negative emotionality versus no-ELS and moderate-ELS groups (p=0.008), with no effects on incentive salience or executive dysfunction (p’s>0.06). In case-control analyses, there were main effects of AUD and ELS (p’s<0.001) on negative emotionality. The AUD group reported greater negative emotionality than controls, and those with high-ELS reported greater negative emotionality than no-ELS or moderate-ELS groups. An AUDxELS interaction on executive dysfunction (p=0.03) revealed controls with no-ELS demonstrated the least executive dysfunction. When ELS was modeled continuously, findings were consistent for negative emotionality, but the AUDxELS interaction for executive dysfunction was not observed (p=0.16). Conclusion Findings support a clinically distinct AUD subtype defined by high-ELS and elevated negative emotionality and suggest independent effects of AUD and ELS on this domain.