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

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.

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.

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.

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.