Brief ReportsHuman plasma glutathione peroxidase and symptom severity in schizophrenia
Introduction
Free radical-mediated pathological processes may have a role in schizophrenia Lohr and Browning 1995, Reddy and Yao 1996, and underlie some previous findings in schizophrenia, specifically our recent findings of red blood cell (RBC) and platelet membrane defects Yao and van Kammen 1994, Yao and van Kammen 1996, Yao et al 1994a, Yao et al 1994b, Yao et al 1996 and other findings of membrane pathology in brains of schizophrenic patients Horrobin et al 1991, Pettegrew et al 1993. Indices of abnormal free radical metabolism have been associated with negative symptoms, tardive dyskinesia, neurological “soft” signs, and Parkinsonian symptoms (Reddy and Yao 1996).
Decreased activity of RBC glutathione peroxidase (GSH-Px), a key antioxidant enzyme, in schizophrenic patients has been reported in some studies Abdalla et al 1986, Stoklasova et al 1985, but not all (Reddy et al 1991). We recently reported that RBC GSH-Px activity was not significantly different between male chronic schizophrenic patients and normal control subjects; however, RBC GSH-Px was significantly higher (p = .037, n = 39, paired t test) after haloperidol withdrawal than during treatment (Yao et al in press b). Moreover, RBC GSH-Px was significantly correlated with psychosis ratings (Yao et al unpublished data).
In addition to the classical GSH-Px, two structure-related proteins are known: phospholipid hydroperoxide GSH-Px (Ursini et al 1985) and human plasma GSH-Px (hpGSH-Px)Maddipati et al 1987, Takahashi et al 1987. To examine whether the findings of GSH-Px defect in the antioxidant defense system extends also to the hpGSH-Px, we applied an enzyme-linked immunoassay method to determine hpGSH-Px in male schizophrenic patients using within-subject, repeated-measures, on–off haloperidol treatment design, compared with age- and gender-matched healthy volunteers. Using the above clinical paradigm, we have reported plasma antioxidant status (Yao et al in press a) and RBC antioxidant enzymes (Yao et al in press b) in essentially the same group of patients and normal control subjects.
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Patients
Male patients (n = 55) were recruited from the VA Pittsburgh Healthcare System. Clinically stable patients who met both DSM-III-R (Spitzer et al 1989) criteria and Research Diagnostic Criteria for schizophrenia were hospitalized, after informed consent. The average age of patients was 39 years (range, 25–49 years), age of onset of illness was 24 years (16–35 years), and duration of illness was 16 years (3–27 years). All patients were admitted to an inpatient research unit for the duration of
Results
hpGSH-Px levels were not significantly different between schizophrenic patients (either haloperidol-treated or drug-free treatment conditions; .111 ± .048 and .111 ± .041 μg/mg protein, respectively) and normal control subjects (.108 ± .043 μg/mg protein). There was no correlation between plasma haloperidol and hpGSH-Px levels. Further, there were no significant differences between on- and off-haloperidol treated (.107 ± .035 and .111 ± .041 μg/mg protein, respectively); <5 weeks and >5 weeks
Discussion
The present data demonstrate that hpGSH-Px was not significantly different between chronic schizophrenic patients relative to matched normal control subjects. These findings are consistent with those previously reported for RBC GSH-Px (see review by Reddy and Yao 1996) and more recently from our laboratory (Yao et al in press b). Similar to RBC GSH-Px, hpGSH-Px is also a selenoprotein catalyzing the reduction of peroxides Maddipati et al 1987, Takahashi et al 1987. Whereas GSH-Px is primarily
Acknowledgements
This study was supported by the Office of Research and Development (Merit Review, JKY), Department of Veterans Affairs, and the Highland Drive VA Pittsburgh Healthcare System.
The authors are grateful to C. Korbanic and L. McElhinny for their technical assistance. Appreciation is also owed to the patients and nursing staff of the Schizophrenia Research Unit under the leadership of Doris McAdam (RN) for their participation and collaboration.
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