Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Katherine A Johnson, Simon P Kelly, Ian H Robertson, Edwina Barry, Aisling Mulligan, Michael Daly, David B Lambert, Caroline McDonnell, Thomas J Connor, Ziarih Hawi, Michael Gill, Mark Andrew Bellgrove

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Abstract

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed time-series analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d ) than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance.
Original languageEnglish
Pages (from-to)927 - 937
Number of pages11
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume147
Issue number6
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

Johnson, Katherine A ; Kelly, Simon P ; Robertson, Ian H ; Barry, Edwina ; Mulligan, Aisling ; Daly, Michael ; Lambert, David B ; McDonnell, Caroline ; Connor, Thomas J ; Hawi, Ziarih ; Gill, Michael ; Bellgrove, Mark Andrew. / Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls. In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2008 ; Vol. 147, No. 6. pp. 927 - 937.
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abstract = "Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed time-series analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d ) than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance.",
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Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls. / Johnson, Katherine A; Kelly, Simon P; Robertson, Ian H; Barry, Edwina; Mulligan, Aisling; Daly, Michael; Lambert, David B; McDonnell, Caroline; Connor, Thomas J; Hawi, Ziarih; Gill, Michael; Bellgrove, Mark Andrew.

In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Vol. 147, No. 6, 2008, p. 927 - 937.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Robertson, Ian H

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AU - Mulligan, Aisling

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AB - Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed time-series analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d ) than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance.

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