HPA-axis function, symptoms, and medication exposure in youths at clinical high risk for psychosis

Increased basal cortisol secretion has been associated with heightened clinical risk for psychosis, and among at-risk individuals, has been variably related to positive and mood symptoms, as well as clinical outcome.

Basal salivary cortisol secretion was assessed in 33 patients at clinical high risk (CHR) for psychosis (21 medication-free and 12 taking a serotonin reuptake inhibitor and/or atypical antipsychotic), and 13 healthy controls. Among the CHR patients, we also examined associations of basal salivary cortisol with symptoms (positive, negative, mood, stress sensitivity) and clinical outcome.

Basal salivary cortisol secretion was significantly higher in CHR patients who were medication-free compared to CHR patients taking medications and to healthy controls. In this small cohort, basal salivary cortisol secretion was associated at trend level with stress sensitivity, and was not significantly related to other symptoms.

Our finding of elevated basal cortisol secretion in CHR patients supports the premise that excess activation of the HPA axis and/or neuroendocrine abnormalities characterize the psychosis risk state for at least a subset of patients. Our findings further suggest that psychotropic medications may have a normalizing effect on HPA-axis dysfunction in CHR patients, which could potentially inform intervention strategies for the prodrome.