Association of the Dopamine D5 Receptor with Attention Deficit Hyperactivity Disorder (ADHD) and Scores on a Continuous Performance Test (TOVA)

Iris Manor, Marylis Corbex, Jacques Eisenberg, Inga Gritsenkso, Rachel Bachner-Melman, Samuel Tyano, Richard P. Ebsteins

Research output: Contribution to journalArticlepeer-review

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 χ2 = 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 χ2 = 16.32, P = 0. 037 when the 148 bp allele was compared to all others (collapsed genotype) that was also significant (χ2 = 59.20, P = 0.025) when all 14 alleles (full genotype) were analyzed. Following methylphenidate, no significant association was observed (χ2 = 12.08, P = 0.147 for 148 bp versus all others) and, similarly, for all 14 alleles (χ2 = 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.

Original languageEnglish
Pages (from-to)73-77
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume127 B
Issue number1
DOIs
StatePublished - 15 May 2004

Keywords

  • Attention deficit hyperactivity disorder (ADHD)
  • Dopamine D5 receptor
  • Microsatellite polymorphism
  • QTDT
  • TOVA

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