Alterations in DHEA metabolism in schizophrenia: Two-month case-control study Michael Ritsner a,b, * , Anatoli Gibel a , Edward Ram c , Rachel Maayan c Abraham Weizman c,d a Acute Department & Clinical Psychobiology Laboratory, Sha’ar Menashe Mental Health Center, Mobile Post Hefer 38814, Hadera, 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 6 March 2005; accepted 21 July 2005 Abstract Objective: The goals of this study were to determine whether alterations in serum dehydroepiandrosterone (DHEA), its sulfated conjugate (DHEAS), androstenedione, testoster- one, and progesterone concentrations occur in schizophrenia patients compared with healthy controls over two months, and their associations with psychopathology, emotional distress, and antipsychotic treatment. Method: Serum hormones were repeatedly determined for 21 antipsychotic-treated male DSM-IV schizophrenia patients and 14 healthy controls. Observations were at four time points: upon entry into the study, and after 2, 4 and 8 weeks. Results: In schizophrenia patients compared with healthy controls serum concentration of DHEA and androstenedione found increased, but that of DHEAS decreased, while progesterone and testosterone showed normal levels. Schizophrenia patients were also characterized by elevated androstenedione / DHEAS molar ratios, and reduced DHEAS / DHEA and testosterone / androste- nedione molar ratios compared with healthy controls. Concentrations and molar ratios of serum hormones did not significantly change during the study either among schizophrenia patients, or healthy controls. Among patients alterations in DHEA, DHEAS and androstenedione were associated with emotional distress, anxiety, dysphoric mood, positive and activation symptoms, serum prolactin levels, but were not related to age, antipsychotic agents, and extrapyramidal side effects. Conclusions: Alterations in DHEA metabolism in schizophrenia are attributed to the 0924-977X/$ - see front matter D 2005 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2005.07.007 * Corresponding author. Acute Department & Clinical Psychobiology Laboratory, 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). KEYWORDS Dehydroepiandroster- one; Progesterone; Androstenedione; Neurosteroids; Prolactin; Schizophrenia; Prospective study European Neuropsychopharmacology (2006) 16, 137 — 146 www.elsevier.com/locate/euroneuro