Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone-sulphate in first-episode schizophrenia: relationship to gender, aggression and symptomatology.

Dehydroepiandrosterone (DHEA) is a major circulating neurosteroid in humans and its administration has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence and activity levels. Since recent findings have suggested the role of neurosteroids in general, and DHEA in particular, in the symptomatology and pharmacotherapy of schizophrenia patients with chronic illness, we investigated DHEA and DHEA-S blood levels in individuals in their first-episode of psychosis in order to exclude effects of age, chronic illness, long-term treatment and institutionalization. Blood levels for DHEA, DHEA-S and cortisol were obtained for 37 first-episode schizophrenia subjects and 27 normal age- and sex-matched controls and correlated with a range of clinical and side-effect rating scales. Baseline DHEA and DHEA-S levels were significantly higher in schizophrenia patients (p<0.05 and p<0.001, respectively). No gender differences were noted in DHEA levels; however, DHEA-S levels were significantly higher in male patients. DHEA-S levels inversely correlated with severity of illness (p<0.05) and aggressive behavior (p<0.05). Patients with higher DHEA-S levels tended to have shorter hospitalizations. Results suggest that individuals in their first-episode of schizophrenia psychosis may develop a neurosteroid response to the first onset of psychosis, which may be associated with a reduction in various adverse clinical features including aggression. Such a putative mechanism may become desensitized with the onset of chronic illness. While preliminary, these results further imply the role of these neurosteroids in the pathophysiology and management of schizophrenia.