Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: The role of stress and of antipsychotic treatment Valeria Mondelli * , Paola Dazzan, Nilay Hepgul, Marta Di Forti, Monica Aas, Alessandro D’Albenzio, Marco Di Nicola, Helen Fisher, Rowena Handley, Tiago Reis Marques, Craig Morgan, Serena Navari, Heather Taylor, Andrew Papadopoulos, Katherine J. Aitchison, Robin M. Murray, and Carmine M. Pariante Institute of Psychiatry, King’s College London, Division of Psychological Medicine, London, United Kingdom Abstract First-episode psychosis (FEP) patients show hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, but the mechanisms leading to this are still unclear. The aim of this study was to investigate the role of stress and antipsychotic treatment on diurnal cortisol levels, and on cortisol awakening response, in FEP. Recent stressful events, perceived stress and childhood trauma were collected in 50 FEP patients and 36 healthy controls using structured instruments. Salivary cortisol was obtained at awakening, at 15, 30, and 60 min after awakening, and at 12 and 8 pm. Patients experienced more recent stressful events, perceived stress and childhood trauma than controls (p < 0.001). Patients had a trend for higher diurnal cortisol levels (p=0.055), with those with less than two weeks of antipsychotics showing significantly higher cortisol levels than both patients with more than two weeks of antipsychotics (p=0.005) and controls (p=0.002). Moreover, patients showed a blunted cortisol awakening response compared with controls, irrespectively of antipsychotic treatment (p=0.049). These abnormalities in patients were not driven by the excess of stressors: diurnal cortisol levels were negatively correlated with the number of recent stressful events (r=-0.36, p=0.014), and cortisol awakening response was positively correlated with a history of sexual childhood abuse (r=0.33, p=0.033). No significant correlations were found between perceived stress or severity of symptoms and cortisol levels, either diurnal or in the awakening response. Our study shows that antipsychotics normalize diurnal cortisol hyper- secretion but not the blunted cortisol awakening response in FEP; factors other than the excess of psychosocial stress explain HPA axis abnormalities in FEP. © 2009 Elsevier B.V. All rights reserved. * Corresponding author. Sections of Perinatal Psychiatry & Stress, Psychiatry and Immunology (SPI-Lab), Centre for the Cellular Basis of Behaviour, The James Black Centre, Institute of Psychiatry, Kings College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom. Tel.: +44 0 20 7848 0726; fax: +44 0 20 7848 0986. valeria.mondelli@kcl.ac.uk (V. Mondelli). . Contributors Valeria Mondelli contributed to the study design, recruitment of the subjects, data collection, analysis and interpretation, and writing of the manuscript. Paola Dazzan, Marta Di Forti, Helen Fisher, Craig Morgan, Kathy J. Aitchison, Robin M. Murray and Carmine M. Pariante contributed to the study design, analysis and interpretation of the data, and writing of the manuscript. Nilay Hepgul, Monica Aas, Alessandro D’Albenzio, Marco Di Nicola, Rowena Handley, Tiago Reis Marques, Serena Navari and Heather Taylor contributed to the recruitment of the subjects, collection of the data and wiring of the manuscript. Andrew Papadopoulos contributed to the analysis of the cortisol samples, interpretation of the data and writing of the manuscript. Conflict of interest All other authors declare that they have no conflicts of interest. Europe PMC Funders Group Author Manuscript Schizophr Res. Author manuscript; available in PMC 2012 December 04. Published in final edited form as: Schizophr Res. 2010 February ; 116(2-3): 234–242. doi:10.1016/j.schres.2009.08.013. Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts