Dopamine Transporter Genotype and Stimulant Dose-Response in Youth with Attention-Deficit/Hyperactivity Disorder

Abstract

This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD). Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS. Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype. ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.