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World J Biol Psychiatry. 2017 Dec 15:1-10. doi: 10.1080/15622975.2017.1410221. [Epub ahead of print]

DRD4 exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate.

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a Department of Human Genetics , McGill University , Montreal , QC , Canada.
b Douglas Mental Health University Institute , Verdun , QC , Canada.
c Department of Psychiatry , McGill University , Montreal , QC , Canada.
d Department of Neurology and Neurosurgery , McGill University , Montreal , QC , Canada.



Dopamine plays an important role in modulating attention and motor behaviours, dimensions altered in attention deficit/hyperactivity disorder (ADHD). Numerous association studies have linked dopamine receptor 4 (DRD4) to increased risk of ADHD. This study investigated the effect of DRD4 exon 3 polymorphism on child behaviours in response to treatment with methylphenidate.


A total of 374 children diagnosed with ADHD (ages 6-12 years) were evaluated under three experimental conditions: baseline, placebo and MPH (0.5 mg/kg/day). This was a 2-week prospective within-subject, placebo-controlled, crossover trial. The Conners' Global Index for parents and for teachers was used to evaluate the behaviours of the children. One-way repeated measures analysis of variance was used to test the effect of the interaction between DRD4 genotype and experimental conditions.


A significant interaction between DRD4 genotype and treatment was detected when the child's behaviour was evaluated by the parents (P = 0.035, effect size of 0.014), driven by a better treatment response in children homozygous for long 7-repeat allele.


According to the parent assessment, children homozygous for the long 7-repeat allele were more responsive to experimental condition. This is the largest pharmacogenetic investigation of the effect of DRD4 exon 3 polymorphism in childhood ADHD.

TRIAL REGISTRATION:, identifier NCT00483106.


ADHD; DRD4 7-repeat; methylphenidate; pharmacogenetics; treatment response

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