Sex differences in prevalence and clinical correlates for psychotic symptoms in first-episode drug-naïve patients with bipolar disorder: a cross-sectional study

BACKGROUND: Psychotic symptoms, which affect a significant proportion of patients with bipolar disorder (BD), are associated with adverse prognostic outcomes. Currently, sex-specific patterns of psychotic symptoms remain inadequately characterized in BD. This study seeks to investigate sex-based differences in psychotic symptoms among first-episode drug-naïve (FEDN) BD patients among Han Chinese population. METHODS: A total of 577 FEDN BD patients, comprising 271 males and 306 females, were recruited in this study. Demographic characteristics were collected using a specialized questionnaire. The positive subscale of the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Scale, Young Mania Rating Scale, and Clinical Global Impression Scale-Severity of Illness were used to evaluate clinical symptoms. Moreover, fasting blood glucose, prolactin, lipids, and thyroid hormone levels, alongside metabolic syndrome (MetS) were assessed. RESULTS: The prevalence of psychotic symptoms showed no significant sex differences in the FEDN BD cohort (p = 0.968). Nevertheless, multiple linear regression revealed that MetS score (p = 0.001) was significantly associated with the PANSS Positive subscale score (PANSS-P) among males, whereas thyroid-stimulating hormone (TSH) levels (p < 0.001) and high-density lipoprotein cholesterol (HDL-C) levels (p < 0.001) were significantly associated with PANSS-P among females. Binary logistic regression revealed that MetS score (p = 0.002) was a significant correlate of the prevalence of psychotic symptoms among males only, whereas TSH levels (p < 0.001) significantly correlated with the prevalence of psychotic symptoms among females only. CONCLUSIONS: Among Han Chinese FEDN BD patients, our study revealed the following: (1) No significant sex difference was observed in the prevalence of psychotic symptoms; (2) HDL-C functions as a meaningful protective factor against the prevalence of psychotic symptoms in both males and females, while its association with symptom severity is observed exclusively in females; (3) Sex-specific indicators correlate with psychotic symptoms, specifically MetS dominates in males, while TSH in females. Our results call for sex-informed clinical protocols that integrate metabolic-endocrine monitoring and targeted interventions to reduce psychosis risk in BD.