Altered glutathione redox state in schizophrenia

Issue title: Disease Markers of the Nervous System

Article type: Research Article

Authors: Yao, Jeffrey K.^{; ;} | Leonard, Sherry | Reddy, Ravinder^;

Affiliations: VA Pittsburgh Healthcare System, 7180 Highland Drive, Pittsburgh, PA 15206, USA | Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA | Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA | VA Denver Health-care System, Denver, CO and Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, USA

Note: [] Corresponding author: Jeffrey K. Yao, Ph.D., FACB, VA Pittsburgh Healthcare system (Bldg. #13), 7180 Highland Drive, Pittsburgh, PA 15206, USA. Tel.: +1 412 365 4465; Fax: +1 412 365 5917; E-mail: jkyao@pitt.edu

Abstract: Altered antioxidant status has been reported in schizophrenia. The glutathione (GSH) redox system is important for reducing oxidative stress. GSH, a radical scavenger, is converted to oxidized glutathione (GSSG) through glutathione peroxidase (GPx), and converted back to GSH by glutathione reductase (GR). Measurements of GSH, GSSG and its related enzymatic reactions are thus important for evaluating the redox and antioxidant status. In the present study, levels of GSH, GSSG, GPx and GR were assessed in the caudate region of postmortem brains from schizophrenic patients and control subjects (with and without other psychiatric disorders). Significantly lower levels of GSH, GPx, and GR were found in schizophrenic group than in control groups without any psychiatric disorders. Concomitantly, a decreased GSH:GSSG ratio was also found in schizophrenic group. Moreover, both GSSG and GR levels were significantly and inversely correlated to age of schizophrenic patients, but not control subjects. No significant differences were found in any GSH redox measures between control subjects and individuals with other types of psychiatric disorders. There were, however, positive correlations between GSH and GPx, GSH and GR, as well as GPx and GR levels in control subjects without psychiatric disorders. These positive correlations suggest a dynamic state is kept in check during the redox coupling under normal conditions. By contrast, lack of such correlations in schizophrenia point to a disturbance of redox coupling mechanisms in the antioxidant defense system, possibly resulting from a decreased level of GSH as well as age-related decreases of GSSG and GR activities.

Keywords: Glutathione, glutathione disulfide, glutathione peroxidase, glutathione reductase, cigarette smoking, age, postmortem caudate, schizophrenia

Journal: Disease Markers, vol. 22, no. 1-2, pp. 83-93, 2006