title: Effects of two dopamine-modulating genes (DAT1 9/10 and COMT Val/Met) on n-back working memory performance in healthy volunteers.
abstract: BACKGROUND
  Impairments in working memory are present in many psychiatric illnesses such as attention-deficit hyperactivity disorder (ADHD) and schizophrenia. The dopamine transporter and catechol-O-methyltransferase (COMT) are proteins involved in dopamine clearance and the dopamine system is implicated in the modulation of working memory (WM) processes and neurochemical models of psychiatric diseases. The effects of functional polymorphisms of the dopamine transporter gene (DAT1) and the COMT gene were investigated using a visuospatial and numerical n-back working memory paradigm. Our n-back task was designed to reflect WM alone, and made no demands on higher executive functioning.
  
  
  METHODS
  A total of 291 healthy volunteers (aged 18-45 years) were genotyped and matched for age, sex, and Barratt Impulsivity Scale (BIS) and National Adult Reading Test (NART) scores. To assess individual gene effects on WM, factorial mixed model analysis of variances (ANOVAs) were conducted with the between-subjects factor as genotype and difficulty level (0-, 1-, 2- and 3-back) entered as the within-subjects factor.
  
  
  RESULTS
  The analysis revealed that the DAT1 or COMT genotype alone or in combination did not predict performance on the n-back task in our sample of healthy volunteers.
  
  
  CONCLUSIONS
  Behavioral effects of DAT1 and COMT polymorphisms on WM in healthy volunteers may be non-existent, or too subtle to identify without exceedingly large sample sizes. It is proposed that neuroimaging may provide more powerful means of elucidating the modulatory influences of these polymorphisms.
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Blanchard
authors.forename: S R
authors.initials: SR
authors.lastname: Chamberlain
authors.forename: J
authors.initials: J
authors.lastname: Roiser
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.forename: U
authors.initials: U
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D002394:Catechol O-Methyltransferase