Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects Michael Ritsner a,b, ⁎ , Rachel Maayan c , Anatoly Gibel a , Abraham Weizman c,d a Sha'ar Menashe Mental Health Center, Mobile Post Hefer 38814, Israel b Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel c Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Beilinson Campus, Petah Tikva, Israel d Research Unit, Geha Psychiatric Hospital, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Received 4 May 2006; received in revised form 15 September 2006; accepted 5 October 2006 Abstract Background and objective: Contradictory and confusing reports on serum dehydroepiandroster- one (DHEA) levels in schizophrenia led us to compare the serum concentration of its precursor, pregnenolone (PREG), between medicated schizophrenia patients and healthy subjects. The neurosteroid levels were monitored for two months and the relationship of these neurosteroids with schizophrenic symptomatology, emotional distress, and anxiety was examined. Method: We determined blood levels of PREG, and DHEA in 15 schizophrenia patients and 12 healthy controls at four time points: at the start of the study, after 2, 4 and 8 weeks. Analysis of covariance and canonical correlations across four time points were applied. Results: Controlling for age, serum concentrations of PREG were lower, while the DHEA level and the molar ratio values of DHEA/PREG were higher in schizophrenia patients compared to healthy controls. Both levels of PREG and DHEA and their molar ratio did not change significantly during the study's period either among schizophrenia patients or healthy controls. The blood levels of PREG appear to be associated with trait-anxiety scores in the schizophrenia patients, while associations of clinical symptoms with two neurosteroids did not reach a significant level when the confounding effect of emotional distress, and anxiety scores was controlled. Conclusion: Low serum pregnenolone concentrations in schizophrenia appear to be associated with trait-anxiety scores independent of symptoms. Further research into the role of pregnenolone in schizophrenia is warranted. © 2006 Elsevier B.V. and ECNP. All rights reserved. KEYWORDS Pregnenolone; Dehydroepiandrosterone; Neurosteroids; Schizophrenia; Anxiety; Emotional distress 1. Introduction Pregnenolone (PREG) and its principal metabolite dehydroe- piandrosterone (DHEA) are neurosteroids: they have ⁎ Corresponding author. Sha'ar Menashe Mental Health Center, Mobile Post Hefer 38814, Hadera, Israel. Tel.: +972 4 6278750; fax: +972 4 6278045. E-mail address: ritsner@shaar-menashe.org.il (M. Ritsner). 0924-977X/$ - see front matter © 2006 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2006.10.001 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2007) 17, 358—365