DRD4 exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate. (3rd July 2019)

• Record Type: Journal Article
• Authors: Naumova, Darya; Grizenko, Natalie; Sengupta, Sarojini M.; Joober, Ridha
• Is Part Of: World journal of biological psychiatry. Volume 20:Number 6(2019)
• Page Start: 486
• Page End: 495
• Publication Date: 2019-07-03
• Subjects: ADHD -- DRD4 7-repeat -- methylphenidate -- pharmacogenetics -- treatment response; Biological psychiatry -- Periodicals; Biological Psychiatry -- Periodicals; 616.89
• DOI: 10.1080/15622975.2017.1410221
• Languages: English
• ISSNs: 1562-2975

Abstract

Abstract: Objectives: 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. Methods: 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. Results: 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. Conclusions: 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: clinicaltrials.gov, identifier NCT00483106.