The Significance Of Free Radical Injuries In Psychopathology In Patients With Schizophrenia

OBJECTIVES:Up to now, the pathogenesis of schizophrenia is still unclear. There are a number of hypotheses that have been suggested to explain its etiological basis. Increasing evidence revealed that free radical-mediated central nervous system (CNS) neuronal dysfunction was involved in the pathophysiology of schizophrenia. Free radicals (oxyradicals, such as superoxide, hydroxyl, and nitric oxide) cause cell injury when they are generated in excess or the antioxidant defense function is impaired. Both of these processes seem to be affected in schizophrenia. In this study, we systematically measured the contents or activity of oxyradical scavengers and nitric oxide in the plasma or erythrocytes of patients with schizophrenia and controls.METHODS: 83 drug-naive patients (42 male and 41 female, age range 16-48, mean age 26.4?.3) and 90 age and sex-matched normal volunteers (45 male and 45 female, age range 16-50, mean age 27.8?.9) were included to measure the contents of nitric oxide (P-NO), lipid peroxide (P-LPO), vitamin C (P-VC), vitamin E (P-VE), beta-carotene (P- P -CAR) in their plasma,and the activity of superoxide dismutase (E-SOD), catalase (E-C AT), glutathione peroxidase (E-GSH-Px) in their erythrocytes; These itemswere remeasured in 36 patients after 4 weeks treatment with clozapine, risperidone, olanzapine. All patients were evaluated by Positive And Negative Syndrome Scale (PANSS) before and after treatment.RESULTS: Three enzymes activity and the contents of P-VC, P-VE, P-P -CAR were founded to be significantly lower in the patients than in the normal controls(P<0.001); the results also showed a marked increase in the contents of P-LPO and E-LPO(P<0.001); the patients had significantly higher contents of P-NO compared to the controls(P<0.001). In the patients under twenty , the average value of P-NO positively correlated with the value of Total Scale (TS) of PANSS , that of P-β-CAR negatively correlated with the value of TS; the values of P-NO, P-LPO, E-LPO positively correlated with the value of Positive Scale (PS) of PANSS, those of P-VC, P-VE, P- P -CAR, E-SOD, E-GSH-Px negatively correlated with the value of PS; there was no correlation between all indexes with the value of Negative Scale (NS) and General Scale(GS) of PANSS. Along with the growth of age, the number of indexes that correlated with the value of scales reduced gradually. After 4 weeks treatment ,the average levels of P-NO, P-LPO, E-LPO decreased ,while those of E-SOD, E-CAT, E-GSH-Px, P-VC, P-VE, P- P -CAR increased.CONCLUSIONS: The results of this study were in agreement with the hypothesis that there is not one but several kinds of neurotransmitter abnormalities in the patients with schizophrenia. Free radical (oxyradicals and nitric oxide) injuries may play a mediating role in the psychopamologyof schizophrenia that was caused by the abnormalities of dopamine and glutamic acid.