The Association Between BDNF Levels and Risperidone-induced Weight Gain is Dependent on the BDNF Val66Met Polymorphism in Antipsychotic-naive First Episode Schizophrenia Patients: a 12-week Prospective Study

A growing number of studies have shown that brain-derived neurotrophic factor (BDNF) is associated with weight gain during antipsychotic treatment in schizophrenia patients. However, there is still a lack of research results in the initial stage of antipsychotic treatment. This study aimed to evaluate the relationship between weight gain caused by risperidone monotherapy for 12 weeks and BDNF level in antipsychotic-naive and first-episode (ANFE) patients with schizophrenia, and we hypothesize that this may depend on BDNF Val66Met gene polymorphism. In a 12-week longitudinal trial, 225 ANFE patients were enrolled and treated with risperidone. Body weight was measured at baseline and during the 12-week follow-up. After treatment, the average weight of ANFE patients increased by 2.6 kg. Furthermore, we found that in patients with Val/Val genotype, the increase in serum BDNF levels was negatively correlated with risperidone-induced weight gain (r = -0.44, p = 0.008). Regression analysis showed that the baseline BDNF level was a predictor of weight gain after treatment (β = -0.45, t = -3.0, p = 0.005). Our results suggest that the BDNF signaling may be involved in weight gain caused by risperidone treatment. Furthermore, the negative association between weight gain and increased BDNF levels during risperidone treatment in ANFE schizophrenia depends on the BDNF Val66Met polymorphism.