Progress in Neuro-Psychopharmacology and Biological Psychiatry
Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings
Introduction
Reactive oxygen species (ROS) are oxygen-containing molecules that have a higher reactivity than ground state molecular oxygen. ROS include free radicals such as the superoxide anion radical (O2−) and the hydroxyl radical (.OH), and molecules such as singlet oxygen (1O2) and hydrogen peroxide (H2O2). Free radicals, formed in tissues, have very short half-lifes, and thus determination of their levels is difficult (Kuloglu et al., 2002). However, they can be evaluated indirectly by the measurement of antioxidant enzyme levels such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and plasma Thiobarbituric Acid Reactive Substances (TBARS) as an indicator of free radical-induced lipid peroxidation (Halliwell, 1999, Gutteridge and Halliwell, 2000).
Recently, there has been abundant evidence that free radicals are involved in membrane pathology in the central nervous system (CNS) and may play a role in many diseases such as schizophrenia (Lohr, 1991, Mahadik and Mukherjee, 1996, Yao et al., 2001, Yao et al., 2004, Reddy et al., 2003, Fendri et al., 2006). Schizophrenia, a serious hereditary disease, is a biological disorder of the brain resulting from abnormalities that arise early in life and disrupt normal development of the brain. The chemical nature of the schizophrenic brain is still not completely understood. Oxidative stress damage might be the biochemical basis of the neurodevelopmental abnormalities in schizophrenia (Horrobin, 1998).
Observations on the role of oxidative stress, the imbalance between the formation of reactive oxygen species and the activity of Antioxidant Defense System (AODS) in schizophrenia have been controversial (Reddy et al., 1991, Mahadik and Mukherjee, 1996, Reddy and Yao, 1996, Kuloglu et al., 2002, Reddy et al., 2003). Impaired antioxidant enzyme defense and increased lipid peroxidation have been reported in chronic-medicated (Herken et al., 2001, Khan et al., 2002) and in drug-naïve first-episode schizophrenic patients (Mukherjee et al., 1996, Mahadik et al., 1998, Reddy et al., 2003).
Large numbers of studies have shown that schizophrenia runs in families, that is, the morbid risk of developing schizophrenia increases with the greater genetic relatedness to an individual with the disorder (Hovatta et al., 1997, Tsuang et al., 1999). No known reports relate to oxidative stress markers in genetically vulnerable subjects, such as first degree relatives of schizophrenic patients.
In the present study, Red Blood Cell (RBC) antioxidant enzyme (SOD, GSH-Px and CAT) activities and plasma TBARS were determined in clinically stable patients with schizophrenia and their unaffected siblings.
Section snippets
Methods
A case-controlled study was conducted during the first semester 2003 in a collaboration between the Biophysics Laboratory of the Faculty of Medicine and the Psychiatry Department of the University Hospital of Monastir.
Antioxidant enzyme activities
RBC antioxidant activities of SOD and CAT were not related to age and not affected by gender or smoking for each group, whereas RBC antioxidant GSH-Px activity correlated positively with age in unaffected siblings of schizophrenic patients (r = 0.41, P = 0.02) and in control subjects (r = 0.37, P = 0.06). Thus, differences in the RBC antioxidant GSH-Px activity between the study groups were tested by performing an ANOVA, adjusted by age. Schizophrenic patients and their unaffected siblings had
Discussion
The major findings of the present study were that (1) RBC activities of SOD, CAT and GSH-Px were decreased in clinically stable schizophrenic patients treated with neuroleptics; (2) there were differential alterations in antioxidant enzyme activities in their unaffected siblings; (3) Plasma TBARS were high in schizophrenic patients; (4) Plasma TBARS were not related to RBC antioxidant enzyme activities in all groups. These findings suggest that schizophrenic patients, with the decrease in
Conclusion
The results obtained showed a decrease in antioxidant enzyme activities and an increase in lipid peroxidation confirming the existence of oxidative stress in schizophrenic patients treated with neuroleptics. On the other hand, in unaffected siblings, genetically vulnerable subjects, SOD and CAT levels were significantly lower whereas GSH-Px antioxidant activity was significantly increased compared to control subjects. The increase in GSH-Px antioxidant activity in unaffected siblings may be a
Acknowledgments
We thank the participants in our study and Moncef Rassas (Faculty of Medicine of Monastir) and Susan Gamon (Trace Element- Institute for UNESCO) for their valuable help with an earlier draft of this article.
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