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.
