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Disrupted Antioxidant Enzyme Activity and Elevated Lipid Peroxidation Products in Schizophrenic Patients With Tardive Dyskinesia

J Clin Psychiatry 2007;68(5):754-760

Background: Free radical-mediated pathology has been implicated in the development of tardive dyskinesia (TD). Antioxidant defense system alterations and increased lipid peroxidation have been postulated as a possible mechanism for neuronal damage associated with TD. However, the relationship between antioxidant enzymes, lipid peroxidation products, and the severity of TD symptoms has not been determined within a single patient group.

Method: Plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation, superoxide dismutase, glutathione peroxidase, andcatalase were examined in 80 patients with schizophrenia (DSM-IV criteria) and TD (Schooler-Kane criteria) and 45 schizophrenia patients without TD. Results were compared to those of 50 age-, sex-, and smoking status-matched controls. Tardive dyskinesia severity was assessed using the Abnormal Involuntary Movement Scale, and patient psychopathology was assessed using the Positive and Negative Syndrome Scale.

Results: Patients with TD had lower plasma superoxide dismutase, glutathione peroxidase, and catalase levels but higher MDA levels than those without TD. In the patients with TD, MDA levels were positively correlated with Abnormal Involuntary Movement Scale total score and with Positive and Negative Syndrome Scale negative subscore. Superoxide dismutase and catalase activities were inversely correlated with MDA levels.

Conclusions: Our data support the hypothesis that oxidative stress is involved in the pathophysiology of TD. These data also suggest a relationship between oxidative stress and the severity of dyskinesia in TD patients. Increased lipid peroxidation may likely be a result of decreased endogenous antioxidant enzyme activities in TD.