Dopamine-related genotypes and the dose-response effect of methylphenidate on eating in attention-deficit/hyperactivity disorder youths

Abstract

Objective: There are individual differences in the effects of methylphenidate (MPH), a dopamine (DA) transport inhibitor, on appetite in children with attention-deficit/hyperactivity disorder (ADHD). One potential moderating factor is variation in brain DA activity, which is influenced by dopamine-related genes: the DA transporter (DAT) (SLC6A3), the DA D2 receptor (DRD2), and the DA D4 receptor (DRD4) genes. The purpose of this study was to explore the relationship between dopamine-related gene polymorphisms and food consumption in ADHD children receiving varying doses of MPH. Methods: In a randomized, within-subject, double-blind design, 58 ADHD children (ages 6-12 years) received placebo, 0.15, 0.3, or 0.6mg/kg of MPH three times daily over 9 weeks. Observations of percent lunch consumed as a function of dopamine-related genotypes and MPH dose were analyzed using mixed effects regression models. Results: A significant dose-response reduction in eating was observed across all genotypes (p<0.001). There was an interaction of DAT SLC6A3 and DRD2 genotypes and dose, because 9/9 DAT children showed a stronger effect of dose when compared with the 9/10 and 10/10 children (p<0.001) and DRD2 A2/A2 children showed a stronger effect of dose when compared with A1/A1 and A1/A2 children combined (p=0.007). There was no significant interaction of dose by DRD4 genotype. Conclusions: Lunch consumption decreased as a function of MPH dose. DA-related genotypes associated with greater brain DA signaling moderated the influence of drug on consumption. These results provide information relevant to predicting which children are likely to experience the greatest appetite suppression when taking MPH. © 2009, Mary Ann Liebert, Inc.