Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA)

Am J Med Genet B Neuropsychiatr Genet. 2004 May 15;127B(1):73-7. doi: 10.1002/ajmg.b.30020.

Abstract

Towards further clarifying the role of dopamine D5 receptor (DRD5) microsatellite polymorphism in the etiology of ADHD, we used a robust family based strategy to test for association between DRD5 and this disorder. Additionally, a neuropsychological mechanism by which this allele may confer risk was explored by examining the relationship between DRD5 genotype and scores on a continuous performance test. DNA was obtained from 164 probands and their parents. Additionally, the majority of these probands were administered a computerized continuous performance test, the Test Of Variables of Attention (TOVA). We first confirmed preferential transmission (TDT chi(2) = 7.02, P = 0.008) of the 148 base pair allele in 155 informative transmissions (94 transmitted and 61 non-transmitted 148 bp allele). Additionally, we used a family-based association test (FBAT) and observed significant multivariate association using FBAT between TOVA scores before methylphenidate administration and the DRD5 microsatellite polymorphism across all four TOVA variables: multi-allelic, multivariate test chi(2) = 16.32, P = 0.037 when the 148 bp allele was compared to all others (collapsed genotype) that was also significant (chi(2) = 59.20, P = 0.025) when all 14 alleles (full genotype) were analyzed. Following methylphenidate, no significant association was observed (chi(2) = 12.08, P = 0.147 for 148 bp versus all others) and, similarly, for all 14 alleles (chi(2) = 47.18, P = 0.343). In summary, the main finding of this report is that the DRD5 repeat polymorphism confers a small but significant risk for ADHD consistent with previous reports. Provisional results in this single investigation suggest that the DRD5 microsatellite also affects performance scores on the TOVA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Child
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D1 / genetics*
  • Receptors, Dopamine D5
  • Task Performance and Analysis

Substances

  • DRD5 protein, human
  • Receptors, Dopamine D1
  • Receptors, Dopamine D5
  • DNA