Alcohol misuse and negative emotion processing in neurotypical drinkers: Sex differences in behavioral and neural markers

Negative emotion contributes to problem drinking. Men and women may differ in the mechanisms of negative emotion processing and the pathophysiology of alcohol misuse. However, few have investigated sex-differences in the impact of alcohol misuse on negative emotion processing. We addressed this issue in a community sample of 148 drinkers (71 women) evaluated with Alcohol Use Disorder Identification Test (AUDIT; men/women 4.4±5.4/4.2±5.6, mean±SD) and functional imaging in a Hariri task. Men and women did not differ in reaction time (RT Neg-Neu ) in matching negative vs. neutral images. Linear regression revealed significant sex-differences, with men showing faster but women showing longer RT Neg-Neu in correlation with AUDIT score. Whole-brain regression identified bilateral middle frontal gyrus (MFG) with activities (β’s) each showing positive and negative correlation with AUDIT score, in men and women, respectively. We tested whether the MFG activity supports downstream motor or higher-level cognitive processes in relation to alcohol use driven by negative emotions, in models with RT Neg-Neu and the Inventory of Drinking Situations 42 Negative Emotions (IDS42-NE) score, respectively, as the dependent variable. The latter model showed a significant sex interaction, with the MFG β and IDS42-NE score negatively and positively correlated in women and in men, respectively. Together, these findings suggest sex differences in negative emotion processing in link with alcohol misuse. Women relative to men appeared more vulnerable to the interference of negative emotion, as reflected in higher RT Neg-Neu , and showed diminished prefrontal cortical activation in association with individual differences in the impact of negative emotion on problem drinking.