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Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents

Molecular Psychiatry volume 14, pages 348–349 (2009)Cite this article

A polymorphism within the catechol-O-methyltransferase (COMT) gene results in valine (Val) to methionine (Met) substitution, with the Met158 allele having lower enzymatic activity giving increased synaptic dopamine in prefrontal cortical regions where the gene is heavily expressed.1 There is mixed evidence linking this increased dopamine to enhanced cognitive performance and more ‘efficient’ underlying cortical activity in Met158 carriers.2, 3 Few studies have examined possible neuroanatomic effects, most only at a lobar volumetric level, and none has included a pediatric population, nor longitudinal data that afford an opportunity to detect age-related gene effects.4, 5, 6, 7, 8 Here we demonstrate a ‘dosage’ effect of the Met158 allele, with a stepwise increase in cortical thickness of the right inferior frontal and superior temporal gyrus with increasing numbers of Met158 allele, and that this genotype effect is developmentally stable.

We genotyped 206 unrelated children and adolescents using standard methods,9 and acquired 464 T1-weighted spoiled gradient recalled neuroanatomic scans on the same 1.5 T GE scanner (for methodological details see Shaw et al.10). Following linear registration to standardized space and correction for nonuniformity artifacts, MR volumes were tissue segmented, and the inner and outer cortical surfaces were then extracted using deformable models, blurred, and cortical thickness was measured in native space at 40 960 vertices. There were 41 Val158 allele homozygotes, 113 Met158 heterozygotes, and 52 Met158 homozygotes. All had at least one neuroanatomic image (mean age 11.1 years, s.d. 3.9 years); 136 (66%) had at least two (mean age 13.1, s.d. 4 years); 79 (38%) had at least three scans (mean age 14.9, s.d. 3.9 years); and 43 (21%) had four or more scans (mean age 17.1 s.d. 3.9 years). Most (54%) were singleton births; the remainder was twin births (one child chosen at random per twin set). The proportion of singleton births did not differ significantly by genotype (χ(2)2=2.3, P=0.31). There were 19 male children (46%) in the Val158Val, 63 (56%) in Val158Met, and 35 (67%) in Met158Met group (χ(2)2=4.2, P=0.12). The majority of children were Caucasian (N=177, 86%) and the genotype groups did not differ significantly on ethnic composition (white versus others: χ(2)2=4.0, P=0.13).

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Authors and Affiliations

  1. Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD, USA

    P Shaw, G L Wallace, A Addington, J Rapoport & J N Giedd

  2. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    A Evans

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  1. P Shaw
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  2. G L Wallace
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  3. A Addington
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  5. J Rapoport
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  6. J N Giedd
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Correspondence to P Shaw.

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Shaw, P., Wallace, G., Addington, A. et al. Effects of the Val158Met catechol-O-methyltransferase polymorphism on cortical structure in children and adolescents. Mol Psychiatry 14, 348–349 (2009). https://doi.org/10.1038/mp.2008.121

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