Smoking Affects the Predictive Roles of Antioxidant Enzymes in the Clinical Response to Risperidone in Schizophrenia: A Large-scale Cohort Study

Objectives: There is overwhelming evidence of the relationship between smoking and schizophrenia (SZ). Tobacco smoke is considered to ameliorate the symptoms and reduce the side effects of antipsychotics in SZ patients. However, the underlying biological mechanism by which tobacco smoke improves symptoms in SZ remains unclear. This study was designed to examine the effects of tobacco smoke on antioxidant enzyme activities and psychiatric symptoms after receiving 12-week risperidone monotherapy. Methods: Two hundred and fifteen antipsychotic-naïve first-episode (ANFE) patients were recruited and treated with risperidone for 3 months. The severity of the patient’s symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS) at baseline and at post-treatment. Plasma SOD, GSH-Px, and CAT activities were determined at baseline and follow-up. Results: Relative to nonsmoking patients with ANFE SZ, patients who smoked had higher baseline CAT activity. In addition, among non-smokers with SZ, baseline GSH-Px was associated with clinical symptom improvement, while baseline CAT was associated with positive symptom improvement in smokers with SZ. Conclusion: Our findings demonstrate that smoking affects the predictive role of baseline SOD, GSHPx, and CAT activities on clinical symptom improvement in patients with SZ.