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 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.
Manor
Iris
I
ADHD Unit, Geha Mental Health Center, Petach-Tiqva, & Sackler School of Medicine, Tel-Aviv University, Israel.
Corbex
Marylis
M
Eisenberg
Jacques
J
Gritsenkso
Inga
I
Bachner-Melman
Rachel
R
Tyano
Samuel
S
Ebstein
Richard P
RP
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050641:Receptors, Dopamine D5; D013647:Task Performance and Analysis
C493605:DRD5 protein, human; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D004247:DNA