title: Influence of the COMT genotype on working memory and brain activity changes during development.
abstract: BACKGROUND
  The Valine158Methionine (Val158Met) polymorphism of the COMT gene leads to lower enzymatic activity and higher dopamine availability in Met carriers. The Met allele is associated with better performance and reduced prefrontal cortex activation during working memory (WM) tasks in adults. Dopaminergic system changes during adolescence may lead to a reduction of basal dopamine levels, potentially affecting Met allele benefits during development.
  
  
  METHODS
  We investigated the association of COMT genotype with behavioral (n = 322) and magnetic resonance imaging data (n = 81-84) collected during performance of a visuospatial WM task and potential changes in these effects during development (reflected in age × genotype interactions). Data were collected from a cross-sectional and longitudinal typically developing sample of 6- to 20-year-olds.
  
  
  RESULTS
  Visuospatial WM capacity exhibited an age × genotype interaction, with a benefit of the Met allele emerging after 10 years of age. There was a parallel age × genotype interaction on WM-related activation in the right inferior frontal gyrus and intraparietal sulcus (IPS), with increases in activation with age in the Val/Val group only. Main effects of COMT genotype were also observed in the IPS, with greater gray matter volumes bilaterally and greater right IPS activation in the Val/Val group compared with the Met carriers.
  
  
  CONCLUSIONS
  These results suggest that COMT genotype effects on WM brain activity and behavior are not static during development. The full developmental picture should be considered when trying to understand the impact of genetic polymorphisms on the mature cognition of healthy adult or psychiatric populations.
authors.affiliation: Neuroscience Department, Karolinska Institutet, Retzius väg 8, Stockholm, Sweden. i.dumontheil@gmail.com
authors.forename: Iroise
authors.initials: I
authors.lastname: Dumontheil
authors.forename: Chantal
authors.initials: C
authors.lastname: Roggeman
authors.forename: Tim
authors.initials: T
authors.lastname: Ziermans
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.forename: Hans
authors.initials: H
authors.lastname: Matsson
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Torkel
authors.initials: T
authors.lastname: Klingberg
mesh_terms: D000293:Adolescent; D000483:Alleles; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase