Attenuated cortisol response to acute psychosocial stress in individuals at ultra-high risk for psychosis.

We recently reported that individuals at ultra-high risk for the development of psychosis (UHR) have elevated levels of chronic stress and deficits in the putative protective factors self-esteem, social support and coping skills. The aim of the present study was to assess endocrine and autonomic responses to acute psychosocial stress and their associations with self-ratings of stress and protective factors in individuals at UHR. Twenty-one patients diagnosed with an "at risk mental state" (12 male, 9 female; mean age 20.8 ± 3.27) and 21 healthy age and gender matched community controls were exposed to the Trier Social Stress Test (TSST). Saliva samples for cortisol assessment and measurements of heart rate and blood pressure were taken throughout the testing period. Levels of perceived chronic stress, protective factors and depression were assessed with reference to the preceding month and year (stress only). Compared to healthy controls, individuals at UHR reported significantly higher levels of depression, deficits in protective factors, and a trend for higher chronic stress levels. Cortisol levels and systolic blood pressure during the TSST were significantly lower in the UHR group, while heart rate changes were comparable to controls. Lower cortisol levels in the UHR group were associated with higher self-ratings of stress in the past year and a lower level of education. Attenuated cortisol responses to acute psychosocial stress in the presence of high chronic stress could indicate a desensitization of the HPA axis. Associated poor metabolic and psychological adjustment to stress might increase vulnerability for the development of psychosis.

Sex differences in the cortisol response to awakening in recent onset psychosis.

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.