The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA)

I. Manor, S. Tyano, J. Eisenberg, R. Bachner-Melman, M. Kotler, R. P. Ebstein

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

One particular candidate gene, the dopamine D4 receptor (DRD4), has been the focus of intense study regarding ADHD since the original investigation by La Hoste et al, an observation confirmed by a recent metaanalysis. However, two previous studies from Israel failed to observe this association. We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test, preferential transmission of the short allele. Additionally, we now report the effect of the DRD4 repeat region on the Test Of Variables of Attention (TOVA), a widely used computerized continuous performance test. Probands with the short exon III repeat performed significantly worse on the TOVA measured both by errors of commission and response time variable. Intriguingly, a 'dose effect' was observed. Increasing repeat size is accompanied by a reduced number of errors of commission and a significant difference is observed between the 2 vs 7 repeats. On the whole, our results lend credence to the notion that the relationship between the DRD4 receptor and ADHD is complex and may be reflecting linkage disequilibrium between the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a neighboring locus.

Original languageEnglish
Pages (from-to)790-794
Number of pages5
JournalMolecular Psychiatry
Volume7
Issue number7
DOIs
StatePublished - 2002
Externally publishedYes

Funding

FundersFunder number
Ministry of Health, State of Israel

    Keywords

    • Association
    • Attention deficit hyperactivity disorder
    • Complex genetic
    • Continuous performance test
    • Dopamine D4 receptor
    • Neuropsychological functioning
    • Polymorphism
    • TOVA
    • Transmission disequilibrium test

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