Meta-Analyses Investigating Basal and Stress-Induced Cortisol Levels in Schizophrenia

Abstract

Evidence is accumulating for dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in schizophrenia, with several studies pointing to a central role for cortisol in this severe psychiatric disorder. Elevated cortisol levels in the morning and a blunted cortisol awakening response (CAR) are common findings in patients with schizophrenia compared to healthy controls. However, inconsistent conclusions have been drawn regarding afternoon and evening cortisol levels, as well as with cortisol reactivity to psychosocial and physical stress in schizophrenia. Therefore, we performed meta-analyses comparing patients with schizophrenia to healthy controls on several cortisol outcomes to improve our understanding of HPA axis dysregulation in schizophrenia. Our analyses revealed schizophrenia to be associated with significantly elevated baseline cortisol levels both in the morning and in the evening. However, no significant group differences were found in afternoon cortisol levels and, contrasting previous meta-analytic findings, we also did not find evidence for an altered CAR in schizophrenia. Our results on cortisol stress reactivity indicate a similar pattern of cortisol secretion in patients with schizophrenia and healthy controls in response to mental and physiological stress. Overall, we found meta-analytic evidence of time-specific alterations in baseline cortisol secretion in association with schizophrenia. The lack of differences in cortisol response to stress in our findings should be interpreted cautiously given the paucity of studies investigating mental and physiological stress in schizophrenia. This work highlights the need for further empirical investigation and warrants replication studies related to the current findings in order to gain insight into how schizophrenia and HPA axis functioning are related.