Meta-analysis of blood cortisol levels in individuals with first-episode psychosis

Objective: Schizophrenia is associated with abnormal neuroimmunoendocrine function. There is evidence for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in individuals with first-episode psychosis (FEP). However, some previous meta-analyses have focused on heterogeneous sample sources and patient populations. We performed a meta-analysis of baseline (i.e., one sample) blood cortisol levels in individuals with FEP and minimal exposure to antipsychotics. Method: Articles were identified by searching PubMed, PsycInfo, Web of Science, and Science Direct, and the reference lists of these studies. Results: Twenty-six studies (comprising twenty-seven samples) met the inclusion criteria. Blood cortisol levels were significantly increased in individuals with FEP compared to controls with a small-to-medium effect size (standard mean difference [SMD] = 0.37, 95% CI 0.16-0.57, p < 0.001). In meta-regression analyses, geography was a significant moderator of this association, with larger effects seen in studies conducted in Asia versus the Middle East. Conclusion: We found elevated blood cortisol levels in individuals with FEP, providing additional, complementary evidence for abnormal HPA axis function in this disorder. This finding, which does not inform on mechanism, is consistent with the “neural diathesis-stress” model of psychosis. Given the immunomodulatory effects of cortisol, methodologically rigorous longitudinal studies of cortisol parameters, inflammatory markers, and psychopathology in this patient population are warranted.