title: Associations between COMTVal158Met polymorphism and cognition: direct or indirect effects?
abstract: BACKGROUND
  Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val(158)Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading.
  
  
  METHODS
  COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test.
  
  
  RESULTS
  Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val(158)Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability.
  
  
  CONCLUSIONS
  Associations between COMT Val(158)Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene-gene interactions or the influence of a functional polymorphism near COMT Val(158)Met.
authors.affiliation: Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO BOX 616 (VIJV), 6200 MD Maastricht, The Netherlands. l.krabbendam@sp.unimaas.nl
authors.forename: Lydia
authors.initials: L
authors.lastname: Krabbendam
authors.forename: Pilar
authors.initials: P
authors.lastname: Isusi
authors.forename: Paloma
authors.initials: P
authors.lastname: Galdos
authors.forename: Elena
authors.initials: E
authors.lastname: Echevarria
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Bilbao
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Martin-Pagola
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Jim
authors.initials: J
authors.lastname: Van Os
mesh_terms: D000328:Adult; D000483:Alleles; D001288:Attention; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011930:Reaction Time / Q000235:genetics*; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000175:diagnosis / Q000235:genetics; D014633:Valine / Q000235:genetics*
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine