Sex-specific cognitive profiles and correlations with dimensional symptoms in first-episode major depressive disorder

This study explored sex-related cognitive differences and their associations with clinical symptom in first-episode, drug-naive patients with major depressive disorder (MDD).

We enrolled 410 MDD patients and 287 healthy controls (HCs). Cognitive function across five domains and depressive symptoms were assessed. Multivariate analysis of covariance (MANCOVA) was used to examine the main and interaction effect of diagnosis and sex. Stratified correlation and regression analyses were performed to explore symptoms and cognitive associations by sex.

MDD patients exhibited significant impairments across five cognitive domains. Main effects of diagnosis and sex were significant. A tentative diagnosis × sex interaction was observed for processing speed, while the interaction for executive function was no longer significant after multiple comparison correction. Symptom-cognition associations differed evidently between males and females. In male patients, sleep disturbance was independently associated with poorer processing speed. In females, sleep disturbance showed negative correlations with processing speed, verbal learning, and executive function; anxiety-somatization was weakly positively related to processing speed, verbal learning, and visual learning, and psychomotor retardation was positively associated with attention.

First-episode MDD presents notable cognitive deficits and distinct sex-specific symptom-cognition relationships. These findings provide preliminary evidence for future studies on sex-specific interventions targeting cognitive dysfunction.