Altered levels of circulating GABAergic 5α/β-reduced pregnane and androstane steroids in schizophrenic men

The role of GABAergic pathways in the pathophysiology of schizophrenia is generally accepted. Therefore, the information concerning alterations of the steroid metabolome associated with the disease and/or its treatment is of interest with regard to the pathophysiology of the disease. Hence, we assessed 18 serum steroids and steroid polar conjugates in a group of drug-naive patients (13 adult men) and after 6-months therapy by atypical antipsychotics and age-matched controls (19 men) using gas chromatography-mass spectrometry analysis. This study, for the first time, demonstrates the altered circulating GABAergic steroids in schizophrenic men as well as the effect of the therapy with two types of atypical antipsychotics. The GABAergic androsterone (3α5α) and etiocholanolone (3α5β) are reduced in schizophrenic men but the therapy with atypical antipsychotics reinstates their levels. This reinstatement could be of importance when considering that the GABAergic substances generally improve the well-being of patients. In addition to the unconjugated androsterone, being the most abundant GABAergic steroid in men, most of the other GABAergic steroids also tended to decrease in the patients. By contrast, the conjugated 5β-pregnanolone isomers were elevated in the patients. In conclusion, although schizophrenia status in adult men is associated with unfavorable alterations in neuroactive steroids, the treatment with antipsychotics could at least partly reinstate their circulating levels.