¹Geha Mental Health Center, Petak Tikvah, Israel

²Research Laboratory, S Herzog Memorial Hospital, Jerusalem, Israel

³Child Psychiatry Clinic, S Herzog Memorial Hospital, Jerusalem, Israel

Beersheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel

Correspondence to: Prof R P Ebstein, Research Laboratory, S Herzog Memorial Hospital, PO Box 35300, Jerusalem 91351, Israel. E-mail: ebstein@netmedia.net.il

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,¹ an observation confirmed by a recent metaanalysis.² However, two previous studies from Israel failed to observe this association.^3,4We have now recruited an additional sample and, overall, in the combined sample of 178 triads we observe using the transmission disequilibrium test,^5,6 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.⁷ 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.

Molecular Psychiatry (2002) 7, 790-794. doi:10.1038/sj.mp.4001078

dopamine D4 receptor; attention deficit hyperactivity disorder; polymorphism; association; transmission disequilibrium test; complex genetic; TOVA; continuous performance test; neuropsychological functioning