Oxidative injury and enzymic antioxidant misbalance in schizophrenics with positive, negative and cognitive symptoms.


Uma Devi P and Chinnaswamy P

With its hallucinations, delusions, thought disorder, and cognitive deficits, schizophrenia affects the most basic human processes of perception, emotion, and judgment. Evidence increasingly suggests that schizophrenia is a subtle disorder of brain development and plasticity and oxidative injury contributes largely to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and altered levels of enzymatic antioxidants in schizophrenic patients. However, the status of antioxidants and the extent of lipid peroxidation in erythrocytes have not been investigated so far in schizophrenia patients with different symptoms. In the present study, in order to examine the antioxidant status and lipid peroxidation in the schizophrenics with positive, negative and cognitive symptoms, the activities of three free radical scavenging enzymes glutathione transferase (GST), glucose-6-phosphate dehydrogenase (G6PD), ceruloplasmin ferroxidase (Cp) and the level of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation were analyzed. Results showed that there was a significant increase in GST activity in all the schizophrenics when compared to normal and it was observed that there was a significant decrease in erythrocyte, G6PD and ceruloplasmin ferroxidase levels in patients with schizophrenia, when compared to controls. Schizophrenics with positive symptomology were found to have pronounced decrease in the activities of Cp ferroxidase and statistically more significant decrease in G6PD levels were found in patients with negative symptoms. Further a significant rise in oxidative stress and decreased secondary enzymic antioxidant status was observed in the chronic stage of schizophrenics as compared to those in acute condition. The study showed that the level of malondialdehyde was increased in schizophrenics with positive (163%), negative (137%) and cognitive (132%) symptoms compared to control groups .The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress. The decreased concentrations of the antioxidants status support the hypothesis that lipid peroxidation is an important causative factor in the pathogenesis of schizophrenia. These data reveal that antioxidant defense mechanisms might be impaired in schizophrenic patients. Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments.

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