Sex Effects on the Relationship Between Stress and Psychosis in Schizophrenia

Stress has an important role in schizophrenia symptomology and many stress-related biological and psychological responses are sex-specific. Previous studies have established links between schizophrenia and stress-related hormones, subjectively experienced stress, and history of stressful experiences respectively. We hypothesized that the relationship between stress and psychosis in schizophrenia would be sex-dependent. N=52 patients with schizophrenia (38.4±14.0 years, 37 males) and N=41 healthy controls (45.3±15.4 years, 17 males) were evaluated for stress and symptoms. Stress was quantified by overnight urinary norepinephrine (NE) levels, the Perceived Stress Scale (PSS), the Major Life Events Checklist (MLEs) and the Childhood Trauma Questionnaire (CTQ). Symptoms severity was assessed using the psychosis subscale of the Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptom Scale (BNSS). We examined the relationship between NE, PSS, MLEs, and CTQ and the BPRS psychosis and BNSS total scores and evaluated the significance of sex by stress interaction. Patients had significantly higher PSS, MLEs, and CTQ (all p < 0.05) and trend-level higher NE (p = 0.06) than controls. Significant sex by stress interaction was observed for BPRS psychosis in patients. For male, BPRS psychosis was significantly positively associated with urinary NE (p = 0.004) and the CTQ total score (p = 0.0003). For female, BPRS psychosis was significantly positively associated with total PSS (p = 0.02). Preliminary analyses supported sex-dependent relationship between stress and psychotic symptoms in patients with schizophrenia. Replication in a larger sample was necessary to confirm these sex-dependent relationships.