Absence of the 7-Repeat Variant of the DRD4 VNTR Is Associated With Drifting Sustained Attention in Children With ADHD But Not in Controls

School of Psychology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 09/2008; 147B(6):927-37. DOI: 10.1002/ajmg.b.30718
Source: PubMed


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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Available from: Ziarih Hawi, Oct 13, 2015
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    • "Thirty-two adults with combined-type ADHD who underwent careful clinical assessment as children when taking part in genetic and neuropsychological studies [Brookes and Faraone, 2006; Johnson et al., 2008] were compared with 32 healthy controls matched for age, sex, handedness, and educational level. The IQ during childhood did not significantly differ between groups. "
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    ABSTRACT: Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N = 32) and were paired with age, gender, and education matched healthy controls (N = 32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N = 17) or remitted ADHDs (remitters, N = 15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P < 0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 08/2015; DOI:10.1002/hbm.22944 · 5.97 Impact Factor
    • "This technique partitions participant response variability into two forms: fast-frequency moment-to-moment variability and slowfrequency gradual variability (Johnson, Kelly, et al., 2008). As the name suggests, moment-to-moment variability reflects quick momentary fluctuations in participant responding over the course of the task. "
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    ABSTRACT: Based on attention restoration theory we proposed that micro-breaks spent viewing a city scene with a flowering meadow green roof would boost sustained attention. Sustained attention is crucial in daily life and underlies successful cognitive functioning. We compared the effects of 40-second views of two different city scenes on 150 university students’ sustained attention. Participants completed the task at baseline, were randomly assigned to view a flowering meadow green roof or a bare concrete roof, and completed the task again at post-treatment. Participants who briefly viewed the green roof made significantly lower omission errors, and showed more consistent responding to the task compared to participants who viewed the concrete roof. We argue that this reflects boosts to sub-cortical arousal and cortical attention control. Our results extend attention restoration theory by providing direct experimental evidence for the benefits of micro-breaks and for city green roofs.
    Journal of Environmental Psychology 05/2015; 42. DOI:10.1016/j.jenvp.2015.04.003 · 2.40 Impact Factor
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    • "underlying various psychiatric disorders, including ADHD, with sustained attention as an endophenotypic assay. Searches of the published literature revealed that most studies have focused on dopaminergic genes, such as DAT1, DRD4, and DRD2 (Barnes et al., 2011; Bellgrove & Mattingley, 2008; Johnson et al., 2008). Few studies have analyzed noradrenergic genes. "
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    ABSTRACT: To investigate the genetic contributors to ADHD sustained attention deficit among noradrenergic genes responsible for the synthesis (dopamine-β-hydroxylase gene, DBH), transport (norepinephrine transporter gene, NET1), reception (alpha-2A adrenergic receptor gene, ADRA2A), and metabolism (monoamine oxidase A gene, MAOA) of noradrenalin (NE). A total of 456 children with ADHD and 108 normal controls were included in a digit cancellation test (DCT). DNA was collected from 242 participants and genotyped for 14 single nucleotide polymorphisms (SNPs) of noradrenergic genes. Compared with normal controls, children with ADHD showed a lower total score and higher mean error rate in the DCT, indicating poorer sustained attention function. Analysis of covariance showed an association between MAOA genotypes and ADHD performance in DCT, with poorer performance in risk allele carriers. No association was found for other noradrenergic genes. Children with ADHD presented with a sustained attention deficit compared with normal controls. The sustained attention deficit of children with ADHD may be associated with genetic variant of MAOA. © 2015 SAGE Publications.
    Journal of Attention Disorders 03/2015; DOI:10.1177/1087054715574832 · 3.78 Impact Factor
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