The Sex-Dependent Relationship between Amygdala Activation and Depressive Symptoms with Problematic Drinking

Biol Psychiatry. 2026 Feb 19:S0006-3223(26)00063-6. doi: 10.1016/j.biopsych.2026.02.007. Online ahead of print.

ABSTRACT

BACKGROUND: Although the initiation of alcohol consumption is common in adolescence, some individuals express binge drinking behavior that could lead to harmful consequences such as developing alcohol use disorder later in life. Evidence suggests a relation between depressive symptoms and harmful alcohol consumption that seems to vary depending on sex. Furthermore, amygdala activation in response to negative emotional stimuli has been suggested to influence drinking due to depressive mood states. Therefore, we expected a sex-dependent effect of neuronal activation and depressive symptoms on risky drinking.

METHODS: Here, we test our hypothesis using a large dataset of 19-year-old participants (n= 958) in the IMAGEN study. Amygdala activation during an emotional faces task were extracted and entered into sex-moderated mediation models that also included scores from the Alcohol Use Disorders Identification Test and Adolescent Depression Rating Scale.

RESULTS: Moderated mediation models indicated that amygdala activation was associated with hazardous drinking through enhanced depressive symptoms in males, while amygdala reactivity in females was associated with decreased risky drinking.

CONCLUSIONS: Taken together, our findings reveal sex differences in negative emotional processing in at-risk adolescents. These associations have the potential to inform the development of sex-specific strategies as well as the detection of early neuronal risk factors to effectively curtail alcohol risk behavior.

PMID:41722886 | DOI:10.1016/j.biopsych.2026.02.007