Sex Differences in Verbal Memory Predict Functioning Through Negative Symptoms in Early Psychosis

Abstract

Verbal memory (VM) is one of the most affected cognitive domains in first-episode psychosis (FEP) and is a robust predictor of functioning. Given that healthy females demonstrate superior VM relative to males and that female patients show less-severe illness courses than male patients, this study examined whether normative sex differences in VM extend to FEP and influence functioning. Four hundred and thirty-five patients (299 males, 136 females) with affective or nonaffective psychosis were recruited from a catchment-based specialized FEP intervention service and 138 nonclinical controls (96 males, 42 females) were recruited from the same community. One of the two neurocognitive batteries comprising six cognitive domains (VM, visual memory, working memory, attention, executive function, processing speed) were administered at baseline. In patients, positive and negative symptoms were evaluated at baseline and functioning was assessed at 1-year follow-up. Patients were more impaired than controls on all cognitive domains, but only VM showed sex differences (both patient and control males performed worse than females), and these results were consistent across batteries. In patients, better baseline VM in females was related to better functioning after 1 year, mediated through fewer baseline negative symptoms. Supplemental analyses revealed these results were not driven by affective psychosis nor by age and parental education. Thus, normative sex differences in VM are preserved in FEP and mediate functioning at 1-year follow-up via negative symptoms. This study highlights the importance of investigating sex effects for understanding VM deficits in early psychosis and suggests that sex may be a disease-modifying variable with important treatment implications.

Keywords: outcomes; cognition; first-episode psychosis; sex effects.

Fig. 1.

z-Scores for neurocognitive domains by sex and group. Significant sex difference in verbal memory z-score (p < .01). Significant group difference across all cognitive domains (p < .05).

Fig. 2.

Verbal memory performance by sex and group. (a) Batteries combined. Significant sex difference in verbal memory z-score (p < .01). Significant group difference in verbal memory z-score (p < .01). (b) Wechsler Memory Scale (WMS-III). Significant sex difference in verbal memory z-score (p < .01). Significant group difference in verbal memory z-score (p < .01). (c) CogState Research Battery (CSRB). Significant sex difference in verbal memory z-score (p < .01). Significant group difference in verbal memory z-score (p < .01).

Fig. 3.

Mediation model illustrating association between sex and functioning at 1-year follow-up. For the categorical variable sex, males were coded as 0 and females as 1. Therefore, a positive β value for a₁ (as was reported) indicated that females had greater verbal memory scores compared with males.