Theory of oxidative stress is suggested in the pathophysiology of schizophrenia. To determine the cause of impaired antioxidant defense system in schizophrenia, a meta-analysis was performed by selecting studies published from 1964 to 2021 from Pubmed and Scopus databases. Data were analysed using Comprehensive Meta-Analysis version 2 and calculated effect sizes were compared between unmedicated and medicated patients with schizophrenia and healthy controls. Heterogeneity, publication bias assessments and subgroup analyses of drug-free and drug-naïve patients, and patients treated with atypical and typical antipsychotics were conducted. Subgroup analysis of confounding factors including age, gender, illness duration and patient status was also conducted. We found that glutathione peroxidase (GPx) was significantly decreased in all patients. Significantly lower catalase (CAT), glutathione (GSH) and albumin (ALB) were found in unmedicated patients only. Both groups showed significantly weakened non-enzymatic antioxidant capacity. Subgroup analyses indicated that weakened non-enzymatic antioxidant capacity may be associated with schizophrenia. Antioxidant status was more impaired in drug-free patients compared with other subgroups. This indicated that antipsychotics may improve antioxidant defense system. Although effect sizes were smaller, future studies may focus on the effect of antipsychotic discontinuation. In overall, schizophrenia was associated with impaired antioxidant defense system especially the non-enzymatic antioxidant system.
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