The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD
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RESEARCH
Open Access
The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD Natasha Matthews1*†, Alasdair Vance2†, Tarrant D R Cummins1, Joseph Wagner1, Amanda Connolly2, Jacqueline Yamada2, Paul J Lockhart3, Ajay Panwar4, Robyn H Wallace4,5 and Mark A Bellgrove1
Abstract Background: This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. Methods: One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. Results: Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. Conclusions: The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task. Keywords: Attention-deficit-hyperactivity-disorder, Working memory, COMT
Background Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder, characterized by age-inappropriate symptoms of inattention, motor overactivity and impulsiveness, observed before the age of seven [1]. The disorder has an estimated prevalence of 3-8% in school-aged children [2] and causes significant lifetime academic, social and occupational impairment * Correspondence: [email protected] † Equal contributors. 1 The University of Queensland, Queensland Brain Institute and School of Psychology, St Lucia 4072 Brisbane, Australia Full list of author information is available at the end of the article
[3]. Family, twin and adoption studies suggest a significant genetic contribution to ADHD, with heritability estimates between 70-90% [4]. Despite this strong genetic loading mapping specific genes has proven difficult, in part due to the heterogeneous
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