Antioxidant Enzymes and Weight Gain in Drug-naive First-episode Schizophrenia Patients Treated with Risperidone for 12 Weeks: A Prospective Longitudinal Study

Background: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities. Objective: The activities of plasma superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls. Methods: Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities, and MDA levels were measured at baseline and during follow-up. Results: Compared with healthy controls, the patients showed higher activities of SOD and CAT but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with body weight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparing SOD, CAT, GPx activities and MDA levels between the WG group and the non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in the non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up. Conclusion: These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment.