Cortisol in schizophrenia spectrum disorders: A comprehensive meta-analysis

Schizophrenia spectrum disorders (SSD) are characterized by alterations in cortisol levels across various parameters, including stress reactivity, hair cortisol, and baseline levels, which may be influenced by antipsychotic treatment. To provide a comprehensive overview of cortisol dysregulation in SSD, we conducted meta-analyses assessing (1) the effects of antipsychotic treatment in SSD patients, and additionally comparing cortisol in SSD patients versus healthy controls (HC) (2) following stress induction (metabolic, physiological, psychological stressors), (3) in hair and (4) baseline levels. Systematic literature searches in PubMed, Web of Science, and PsycINFO (November 2024) identified 121 studies (9049 SSD patients) for inclusion. Meta-analytic results revealed that antipsychotic treatment significantly reduced cortisol levels in SSD (k = 16, g = -0.480, 95 % CI [-0.818, -0.142], p = 0.005). Additionally, compared to HC, SSD was associated with reduced cortisol suppression following dexamethasone exposure (k = 9, g = 0.299, 95 % CI [0.091, 0.507], p = 0.005) and with elevated baseline cortisol levels in the morning (k = 71, g = 0.38, 95 % CI [0.210, 0.546], p < 0.001) and evening (k = 11, g = 0.368, 95 % CI [0.076, 0.661], p = 0.014). However, there were no significant group differences in afternoon baseline cortisol, hair cortisol or cortisol reactivity to stress (p > 0.05). These findings offer a detailed understanding of cortisol alterations in SSD and improve our understanding of HPA axis dysregulation in SSD.