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

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 χ 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 χ 2  = 16.32, P  = 0.037 when the 148 bp allele was compared to all others (collapsed genotype) that was also significant (χ 2  = 59.20, P  = 0.025) when all 14 alleles (full genotype) were analyzed. Following methylphenidate, no significant association was observed (χ 2  = 12.08, P  = 0.147 for 148 bp versus all others) and, similarly, for all 14 alleles (χ 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. © 2004 Wiley‐Liss, Inc.