Home > The sex-dependent relationship between amygdala activation and depressive symptoms with problematic drinking.

Rosenthal, Annika and Rothkirch, Marcus and Krasniqi, Samanda and Bode, Erik L and Daedelow, Laura S and Banaschewski, Tobias and Barker, Gareth J and Bokde, Arun L W and Brühl, Rüdiger and Desrivières, Sylvane and Flor, Herta and Garavan, Hugh and Gowland, Penny and Grigis, Antoine and Martinot, Jean-Luc and Paillère Martinot, Marie-Laure and Artiges, Eric and Nees, Frauke and Orfanos, Dimitri Papadopoulos and Poustka, Luise and Smolka, Michael N and Holz, Nathalie and Vaidya, Nilakshi and Walter, Henrik and Whelan, Robert and Wirsching, Paul and Schumann, Gunter and Heinz, Andreas (2026) The sex-dependent relationship between amygdala activation and depressive symptoms with problematic drinking. Biological Psychiatry, 100, (3), pp. 317-325. DOI: 10.1016/j.biopsych.2026.02.007.

External website: https://www.biologicalpsychiatryjournal.com/articl...

BACKGROUND: Although the initiation of alcohol consumption is common during adolescence, some individuals engage in binge drinking behavior that could lead to harmful consequences such as developing alcohol use disorder later in life. Evidence suggests a relationship between depressive symptoms and harmful alcohol consumption that seems to vary depending on sex. Furthermore, it has been suggested that amygdala activation in response to negative emotional stimuli influences 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 tested our hypothesis using a large dataset of 19-year-old participants (n = 958) in the IMAGEN study. Amygdala activation during an emotional faces task was extracted and entered into sex-moderated mediation models that also included scores from the Alcohol Use Disorders Identification Test and the 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.


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