Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD.
OBJECTIVE
Association between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a variant (a 48 bp variable number of tandem repeats) in the dopamine D4 receptor gene (DRD4) has been widely documented. A meta-analysis of 21 studies revealed evidence of significant association. In this article the authors examine whether the DRD4 7-repeat allele is associated with performance on a variety of neuropsychological tasks in children with ADHD.


METHODS
The presence or absence of the 7-repeat allele was determined in 133 drug-naive children 6 to 13 years of age who fulfilled diagnostic criteria for ADHD. These children were then assessed on several neuropsychological tests known to be associated with attention, impulse control, and response inhibition (the Continuous Performance Test, Matching Familiar Figures Test, Go/No Go Task, and Stop Task). Activity levels were assessed with an actigraph. Children with and without at least one 7-repeat allele were compared with each other and with children in a previous population-based study.


RESULTS
Children who had the 7-repeat allele had significantly more incorrect responses on the Matching Familiar Figures Test (16.1 versus 14.3) than children who did not have the allele. Children with the allele also had shorter mean reaction times for incorrect responses on the Matching Familiar Figures Test (846.1 versus 1103.7 msec) and on the Stop Task (116.6 versus 134.1 msec) than children without the allele. Children with the allele also displayed higher activity levels. The children with and without the allele did not differ significantly in number of ADHD symptoms when the symptoms were split into the areas of inattention and hyperactivity/impulsivity. Both groups of children with ADHD were more neuropsychologically impaired than the nonpatient comparison group.


CONCLUSIONS
In children with ADHD, possession of the DRD4 7-repeat allele appears to be associated with an inaccurate, impulsive response style on neuropsychological tasks that is not explained by ADHD symptom severity.
Langley
Kate
K
Department of Psychological Medicine, University of Wales College of Medicine.
Marshall
Lucy
L
van den Bree
Marianne
M
Thomas
Hollie
H
Owen
Michael
M
O'Donovan
Michael
M
Thapar
Anita
A
D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000523:psychology; D007266:Inhibition, Psychological; D008297:Male; D009483:Neuropsychological Tests; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D012720:Severity of Illness Index; D020080:Tandem Repeat Sequences
C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4