Summary: Does a highly reactive brain make someone more likely to drink? New research shows the answer depends on biological sex. Analyzing fMRI and behavioral data from 958 nineteen-year-olds in the IMAGEN study, investigators found that amygdala reactivity—the brain’s response to emotional threat—acts like a double-edged sword: in young males it links to depressive symptoms that predict heavier drinking, while in young females the same neural sensitivity appears to reduce the likelihood of problematic alcohol use.
The study clarifies why prior research on depression-related drinking produced mixed results: the neural pathways that connect emotional processing to alcohol use differ by sex. Understanding these sex-specific mechanisms can improve early identification of risk and inform more effective, targeted prevention strategies.
Key Facts
- Critical Risk Window: Late adolescence and early adulthood are peak periods for hazardous drinking. Although many people “mature out” of heavy alcohol use, early frequent drinking strongly predicts later Alcohol Use Disorder (AUD).
- Sex-Specific Neural Mechanisms: In this sample, amygdala sensitivity produced opposite effects across sexes—feeding depressive symptoms that were associated with greater drinking in males, while in females the same sensitivity correlated with lower drinking, consistent with a threat-avoidance pattern.
- IMAGEN Cohort: The analysis used data from 958 19-year-old participants in the European IMAGEN multisite project, which tracks adolescent brain development with behavioral measures and functional MRI.
- Implications for Prevention: The results indicate that while addressing depressive symptoms is important for everyone, prevention programs may be more effective if they account for sex-specific neural drivers of risk.
Study Overview
Published in Biological Psychiatry, the study examined how the amygdala—an area of the brain involved in processing emotions and detecting threat—responded when participants viewed brief video clips of faces showing threatening expressions. Researchers measured amygdala activation using fMRI and assessed depressive symptoms and hazardous drinking with validated questionnaires, including the Alcohol Use Disorders Identification Test and the Adolescent Depression Rating Scale.
The researchers used moderated mediation models to test whether amygdala reactivity predicted hazardous drinking through depressive symptoms, and whether that pathway differed by biological sex. Overall, males reported higher levels of problematic drinking, while females reported higher depressive symptom scores. Crucially, the amygdala-to-depression-to-drinking pathway was significant in males but not in females. Instead, higher amygdala reactivity in females was linked directly to lower hazardous-drinking scores, consistent with a behavioral tendency to avoid risky or threatening situations.
Lead author Annika Rosenthal, PhD, explains that these findings resolve apparent contradictions in earlier studies: “Some prior reports found depression more predictive of alcohol problems in women, others in men. By examining the underlying brain responses to negative emotion, we identified sex-specific neural origins that help explain those inconsistencies.”
Editor John Krystal, MD, notes that pinpointing this neural mechanism is an important step toward tailored prevention: identifying adolescent males whose amygdala response feeds depressive symptoms could help clinicians offer early coping strategies for social stress and reduce the likelihood they will use alcohol to self-medicate.
Key Questions Answered:
A: Researchers describe this as a “threat-avoidance” profile. A highly sensitive amygdala can create greater caution around social or risky situations. Since binge drinking often involves social or physical risks, an active neural alarm system may discourage engagement in those settings, lowering alcohol risk.
A: The surprising finding was that female participants reported more depressive symptoms overall, but their depression was not linked to amygdala threat reactivity in the same way as males. This implies that the neural origins of depression—and therefore behavioral responses to it—differ between sexes.
A: Not yet. These results are an important step toward identifying neural risk markers, particularly for young males, but clinical application will require more research and careful validation before routine neuroimaging screening could be recommended.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed.
- Additional context was provided by editorial staff.
About this AUD and neuroscience research news
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Image credit: Neuroscience News
Original Research: Open access. “The Sex-Dependent Relationship Between Amygdala Activation and Depressive Symptoms With Problematic Drinking” by Annika Rosenthal et al., on behalf of the IMAGEN Consortium. Biological Psychiatry. DOI: 10.1016/j.biopsych.2026.02.007
Abstract
The Sex-Dependent Relationship Between Amygdala Activation and Depressive Symptoms With Problematic Drinking
Background
Alcohol use typically begins in adolescence, and while many individuals reduce consumption as they age, some engage in binge drinking that raises the risk for later Alcohol Use Disorder. Prior evidence links depressive symptoms to harmful drinking, but sex differences in that relationship have been inconsistent. Because amygdala responses to negative emotional stimuli can influence mood, the authors hypothesized a sex-dependent effect of amygdala activation and depressive symptoms on risky drinking.
Methods
The study analyzed data from 958 nineteen-year-olds in the IMAGEN cohort. Amygdala activation during an emotional faces task was extracted from fMRI data and entered into sex-moderated mediation models along with Alcohol Use Disorders Identification Test scores and Adolescent Depression Rating Scale scores.
Results
Moderated mediation indicated that, in males, higher amygdala activation predicted greater depressive symptoms, which in turn predicted hazardous drinking. In females, higher amygdala reactivity was associated with decreased risky drinking, and the amygdala-to-depression pathway observed in males was not present.
Conclusions
These results reveal sex differences in how negative emotional processing relates to alcohol risk in adolescents. Recognizing sex-specific neural pathways may guide the development of targeted prevention strategies and early detection of neuronal risk factors to reduce hazardous drinking behavior.