Objective The goal of the study was to examine the relationship between DAT1 3′ genotypes and parent ratings of stimulant side effects and to test if children homozygous for the 9 repeat allele of the DAT1 3′ UTR VNTR (DAT1 3′) display a different side effect profile compared with other DAT1 3′ genotypes.
Method Data on adverse events and DAT1 3′ genotypes were combined from two, double-blind, placebo-controlled, crossover studies of methylphenidate conducted in child psychiatric outpatient clinics in Montreal and Washington, DC. Participants were 177 5–16 year olds (mean age 8.99 years, SD 2) with attention deficit hyperactivity disorder. Parents completed the stimulant side effect scale (SERS) after a week of placebo and a week of methylphenidate treatment.
Results Principal components analysis of the SERS resulted in three factors that accounted for 57% of the variance in stimulant side effects: emotionality, somatic complaints and over-focused. Children with the 9/9 genotype displayed higher scores on the emotionality factor during placebo than the 9/10 and 10/10 genotype groups; emotionality scores increased further during methylphenidate treatment (F(2,151) = 3.24, p<0.05). Children with the 10/10 genotype displayed a significant increase in somatic complaint factor scores during methylphenidate treatment relative to the other genotype groups (F(2,150 = 3.4, p<0.05).
Conclusion Children with the 9/10 genotype were less susceptible to adverse effects than either of the homozygous groups who displayed increased susceptibility to different types of adverse events. Pharmacogenetic analysis utilising DAT1 variants shows promise for identifying individuals at increased or decreased risk of poor tolerability.
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