Disturbances of cortisol awakening response in psychotic disorders and at-risk states – a literature review

Background and objective: According to the diathesis-stress model, disturbances of the hypothalamic-pituitary-adrenal (HPA) axis are thought to play a role in the development, onset, and progression of psychosis. The aim of this paper is to present the available body of evidence on the abnormalities of the cortisol awakening response (CAR) in psychotic disorders and at-risk states. Methods: Review of literature from the years 2011-2022 available across three databases (Scopus, PubMed and Google Scholar) was performed. With an aim to: i) ensure that the review covers a wide range of research related to psychotic presentations as manifested in a broad range of clinical populations (from CHR/UHR to full-blown psychosis), and ii) identify the neurobiological background thereof, the following combination of search terms was applied: "chr" OR "uhr" OR "arms" OR "first-episode schizophrenia" OR "psychosis" AND "cortisol" OR "HPA axis" OR "CAR" OR "cortisol awakening response". Results and conclusion: Research suggests that abnormalities of the HPA axis (in this case, disturbances of the CAR) appear to be an important factor in the pathogenesis of psychotic disorders. The cortisol awakening response was blunted in patients with first-episode psychosis or schizophrenia. On the other hand, in subjects with at-risk states, the results were inconclusive. These findings, however, are based on a small number of studies; therefore, more research in this area is required