Original Article

Neuropsychopharmacology (2005) 30, 1913–1922. doi:10.1038/sj.npp.1300747; published online 4 May 2005

Clinical Research

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Michael Ritsner1,2, Anatoly Gibel1, Rachel Maayan3, Yael Ratner1, Edward Ram3, Hassan Biadsy1, Ilan Modai1,2 and Abraham Weizman3,4

  1. 1Sha'ar Menashe Mental Health Center, Hadera, Israel
  2. 2The Rappaport Faculty of Medicine, Technion, Haifa, Israel
  3. 3Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Campus Beilinson, Petah Tikva, Israel
  4. 4Research Unit, Geha Mental Health Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence: Professor M Ritsner, Acute Department, Sha'ar Menashe Mental Health Center, Mobile Post Hefer 38814, Hadera, Israel. Tel: +972 4 6278750; Fax: +972 4 6278045; E-mail: ritsner@shaar-menashe.org.il

Received 28 September 2004; Revised 8 February 2005; Accepted 16 March 2005; Published online 4 May 2005.

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Abstract

Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

Keywords:

dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, neurosteroids, schizophrenia, responsivity to treatment, prospective study

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