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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 hypersecretion but not the blunted cortisol awakening response in FEP; factors other than the excess of psychosocial stress explain HPA axis abnormalities in FEP.

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Background Evidence from animal and human studies suggests that early-life stress such as physical maltreatment has long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis and is associated with blunted HPA axis reactivity in adulthood. Few studies have investigated whether blunted HPA axis reactivity observed in children exposed to early-life stress signals social, emotional, and behavioral problems. Methods Participants were 190 12-year-old children (50.5% males) recruited from the Environmental Risk Longitudinal Twin Study, a nationally representative 1994 to 1995 cohort of families with twins. Cortisol responses to psychosocial stress were measured in maltreated/ bullied (n = 64) and comparison children (n = 126). We ascertained maltreatment and bullying victimization using mothers’ reports and assessed children’s social, emotional, and behavioral problems at ages 5 and 12 using mothers’ and teachers’ reports. Results Piecewise multilevel growth curve analyses indicated that maltreated/bullied and comparison children showed distinct cortisol responses to stress. Specifically, maltreated/bullied children had lower cortisol responses than comparison children who exhibited a significant increase. Lower cortisol responses were, in turn, associated with more social and behavioral problems among maltreated/bullied children. Conclusions These findings provide support for the influence of childhood harm on blunted HPAaxis reactivity and its potential impacton children’s functioning. Our findings emphasize the need to integrate stress biomarkers in guiding prevention efforts for young victims.