Journal Article


Michael Gill
Ian H Robertson
Celine Mullins
Aiveen Kirley
Ziarih Hawi
Katharina Domschke
Mark A. Bellgrove



alleles methionine male physiopathology cognition disorders attention physiology dopamine attention deficit disorder with hyperactivity humans child genotype adolescent polymorphism genetic psychomotor performance female prefrontal cortex enzymology catechol o methyltransferase genetics metabolism

The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD. (2004)

Abstract ADHD is a highly heritable psychiatric disorder of childhood. A functional polymorphism (Val158Met) of the catechol-O-methyltransferase (COMT) gene has attracted interest as a candidate gene for ADHD. The high-activity valine variant of this polymorphism degrades prefrontal dopamine three to four times more quickly than the low-activity methionine variant and could therefore contribute to the proposed hypodopaminergic state in ADHD. Here we tested for association of this polymorphism with ADHD and examined its influence on prefrontal cognition in ADHD. We have previously reported no association of the Val158Met COMT gene polymorphism in 94 Irish ADHD families (Hawi et al. (2000) Am J Med Genet 96:282-284). Here we re-examined this finding with an extended sample of 179 ADHD cases using a family control design. We also examined the performance of children and adolescents with ADHD (n = 61) on a standardised test of sustained attention. Analysis confirmed the absence of an association between the Val158Met COMT gene polymorphism and the clinical phenotype of ADHD. COMT genotype, however, affected prefrontal cognition in ADHD: ADHD children who were homozygous for the valine variant had significantly better sustained attention than those ADHD children possessing at least one copy of the methionine variant. Children possessing the methionine variant performed significantly below age-related norms on tests of sustained attention. Contrary to expectations, the methionine variant of the Val158Met COMT gene polymorphism impaired prefrontally-mediated cognition in ADHD. This effect may be understood by positing a hyper-functioning of prefrontal dopaminergic systems. Against this background, the slower clearance of dopamine associated with the methionine variant of the COMT gene polymorphism may be disadvantageous to cognition in ADHD.
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Full list of authors on original publication

Michael Gill, Ian H Robertson, Celine Mullins, Aiveen Kirley, Ziarih Hawi, Katharina Domschke, Mark A. Bellgrove

Experts in our system

Michael Gill
Trinity College Dublin
Total Publications: 294
Ian H Robertson
Trinity College Dublin
Total Publications: 162
Mark A. Bellgrove
Trinity College Dublin
Total Publications: 39