Risperidone-induced weight gain in referred children with autism spectrum disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C receptor gene.

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70  mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5-16 years) in relation to -759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 ± 0.017 body mass index-standardized z scores (1.84 ± 1.51  kg) versus 0.64 ± 0.35 z (3.23 ± 1.47  kg) for non-T-allele carriers (p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the -759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.