Cortisol awakening response is decreased in patients with first-episode psychosis and increased in healthy controls with a history of severe childhood abuse.

BACKGROUND: Childhood abuse is highly prevalent in psychosis patients, but whether/how it affects hypothalamic-pituitary-adrenal (HPA) axis at the onset of psychosis remains unclear. We aimed to investigate the effects of severity of childhood abuse on HPA axis activity, in first-episode psychosis (FEP) and healthy controls. METHODS: We recruited 169 FEP patients and 133 controls with different degrees of childhood physical and sexual abuse (i.e. no abuse exposure, non-severe abuse exposure, and severe abuse exposure). Saliva samples were collected to measure cortisol awakening response with respect to ground (CARg), increase (CARi) and diurnal (CDD) cortisol levels. Two-way ANOVA analyses were conducted to test the relationships between severity of childhood abuse and psychosis on cortisol levels in individuals with psychosis and healthy controls with and without childhood abuse history. RESULTS: A statistically significant interaction between childhood abuse and psychosis on CARg was found (F(2,262) = 4.60, p = 0.011, ω2 = 0.42). Overall, controls showed a U-shaped relationship between abuse exposure and CARg, while patients showed an inverted U-shaped relationship. CARg values were markedly different between patients and controls with either no abuse history or exposure to severe childhood abuse. No significant differences were found when looking at CARi and CDD. CONCLUSIONS: Our results show a divergent effect of severe childhood abuse on HPA axis activity in patients with first-episode psychosis and in controls. In the presence of exposure to severe childhood abuse, a blunted CARg and a less reactive HPA axis may represent one of the biological mechanisms involved in the development of psychosis.

Hypothalamic-pituitary-adrenal axis and clinical symptoms in first-episode psychosis.

BACKGROUND: Abnormalities in hypothalamic-pituitary-adrenal (HPA) axis activity have been reported in patients with psychosis, but it is still unclear how these are related to the clinical symptomatology. Inconsistent findings have emerged from previous studies on the association between cortisol levels and clinical symptoms. Methodological and/or clinical factors, such as patients' diagnosis or illness phase, might partially account for these inconsistencies. The aim of this study was to investigate the association between HPA axis activity and clinical symptoms in first-episode psychosis, taking into account diagnosis and illness phase. METHOD: Saliva samples were collected in 55 subjects with first-episode psychosis to assess the Cortisol Awakening Response (CAR) and diurnal cortisol levels (AUC-DAY). Severity of symptoms was assessed with the Positive and Negative Syndrome Scale (PANSS). Scores for subscales and symptom dimensions were used as predictors in multivariate analyses in different diagnostic subgroups and in clinically remitted patients. In addition, a systematic review of the literature on this topic was conducted. RESULTS: In subjects with schizophrenia (n=36), the CAR was predicted by the severity of positive symptoms (beta=0.47, p=0.04); in subjects with depressive psychoses (n=8) the CAR was predicted by excitement (beta=0.58, p=0.005), disorganization (beta=0.39, p=0.007) and depressive symptoms (beta=0.32, p=0.005). In patients with bipolar psychoses (n=11) AUC-DAY was predicted negatively by disorganization (beta=-2.82, p=0.009) and positively by excitement (beta=2.06, p=0.009) and positive symptoms (beta=1.28, p=0.02). In the sample in clinical remission (n=9), the CAR was associated with the severity of positive symptoms (beta=1.34, p=0.009) and, negatively, with excitement (beta=-1.05, p=0.04). The systematic review (on a total of 28 papers, including n=1022 patients), found that in patients with psychosis cortisol levels have been associated with the severity of multiple symptom dimensions. CONCLUSIONS: HPA axis activity is associated with the severity of multiple types of symptoms in first-episode psychosis. Patients' diagnosis and clinical phase partially influence these associations.

Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment.

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 60min after awakening, and at 12 and 8pm. 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.