Changes in metabolism and microbiota after 24-week risperidone treatment in drug naïve, normal weight patients with first episode schizophrenia
Objective: This study was to examine the alterations in metabolic parameters, anti-oxidant superoxide dismutase (SOD), inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and microbiota after 24-week risperidone treatment in drug naïve, normal weight, first episode schizophrenia patients; the study further examined the relationship between metabolic changes and changes in microbiota. Methods: Forty-one patients completed the 24-week study and 41 controls were enrolled in this study. Metabolic parameters, SOD, hs-CRP and the copy numbers of 5 fecal bacteria were measured at baseline (both groups) and at different time points (patients only). Results: Patients had significantly lower numbers of fecal Bifidobacterium spp., Escherichia coli, Lactobacillus spp. compared with healthy controls (HC) (ps < 0.001); in contrast, the numbers of fecal Clostridium coccoides group were significantly higher in the patient group compared with HC (p < 0.001). After 24-week risperidone treatment, there were significant increases in body weight, BMI, fasting blood-glucose, triglycerides, LDL, hs-CRP, SOD and HOMA-IR (p < 0.001), significant increases in the numbers of fecal Bifidobacterium spp. and E. coli (ps < 0.001), and significant decreases in the numbers of fecal Clostridium coccoides group and Lactobacillus spp. (ps < 0.001). Hierarchical multiple linear regression analysis shows that after controlling for potential confounding variables, only the changes in fecal Bifidobacterium spp., among 4 types of fecal bacteria, entered into the model and significantly correlated with the changes in weight (unstandardized coefficient B = 4.413, R 2 change = 0.167, p = 0.009) and BMI (B = 1.639, R 2 change = 0.172, p = 0.008) after 24-week treatment. Conclusion: Drug naïve, first episode schizophrenia patients show abnormalities in microbiota composition. Risperidone treatment causes significant changes in certain fecal bacteria, which are likely associated with antipsychotic medication induced metabolic changes.