Sex/gender differences in orbitofrontal cortex reactivity underlying the associations between stress, social relationships, and problematic alcohol use

Background Accumulating evidence suggests that stress, social relationships, and sex/gender differences in brain function, particularly of the orbitofrontal cortex (OFC), may drive problematic alcohol use. How these factors interact to effect alcohol use, and if they do so differently in men and women, has yet to be explored. Methods Using a subsample of the publicly available Human Connectome Project data consisting of young adults with problematic alcohol use (N = 491; 41.75% women, ≥1 symptom of alcohol abuse/dependence), we used a moderated moderation approach to test whether perceived stress and sex/gender moderated the effect of a multidimensional measure of social relationship quality on drinking levels. We subsequently tested whether OFC function moderated these effects. Results We found that in women, higher friendship and companionship had a protective effect on drinking levels, particularly for women under high stress. In contrast, in men, higher friendship and companionship were linked to increased drinking levels under stress. Preliminary evidence suggested that this effect in men was driven by a subgroup of men with higher OFC reactivity to negative emotional faces. Conclusions Our findings suggest that women benefit from friendship and companionship as a form of stress-relief in the context of problematic drinking, whereas men do not, supporting the need of interventions that facilitate emotionally supportive, pro-recovery social environments particularly in men. Preliminary evidence further suggests a role of emotional dysregulation in men. Overall, our findings support the importance of developing sex/gender and neurobiologically informed interventions that target stress-related alcohol use.