Sex versus gender associations with depressive symptom trajectories over 24 months in first-episode schizophrenia spectrum disorders

Background: Females with schizophrenia often experience more severe and persistent depressive symptoms than males, in particular during the acute phase of the illness. In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and depression in schizophrenia. Aim: We examined the associations of sex versus gender with visit-wise changes in depressive symptoms over 24 months in patients with first-episode schizophrenia spectrum disorders (FES) (n = 77) compared to matched healthy controls (n = 64). Methods: The Bem Sex Role Inventory was used to measure feminine gender role endorsement. The Calgary Depression Scale for Schizophrenia was used to measure depressive symptoms at baseline, weeks 2, 4, and 6, and months 3, 6, 9, 12, 15, 18, 21, and 24. We used mixed models for continuous repeated measures to examine the moderating effects of childhood trauma, premorbid adjustment, age of psychosis onset, and cannabis use on the associations of sex and gender with depressive symptoms. Results: Higher feminine gender role endorsement, independent of biological sex, was associated with more severe baseline depression and worse initial treatment trajectories. Childhood trauma exposure was also associated with worse depression outcomes, and mediated the association between gender and pre-treatment depression severities. Conclusions: Gender, but not sex, was associated with depressive symptom trajectories in FES. The consideration of both sex and gender offered a more nuanced insight into depressive symptoms compared to biological sex alone.