title: Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia.
abstract: BACKGROUND
  Neurocognitive deficits are recognized as a cardinal feature of schizophrenia, but the determinants of these deficits remain unknown. Recent reports have suggested that a functional polymorphism, Val(158)Met in exon III of the catechol-O-methyltransferase gene, shares approximately 4% variance with performance on the Wisconsin Card Sorting Test. These findings led to suggestions that the catechol-O-methyltransferase polymorphism may exert its effects by modulating prefrontal dopamine function, but few other neurocognitive measures have been examined, leaving open questions about phenotypic specificity.
  
  
  METHODS
  We examined the effects of the catechol-O-methyltransferase Val(158)Met polymorphism in 58 individuals with chronic schizophrenia who completed a battery of 15 neurocognitive tests, which were reduced to four reliable neurocognitive domain scores. We examined the effects of genotype on these four domains and on global neurocognitive ability.
  
  
  RESULTS
  The Met allele was associated with better performance in the Processing Speed and Attention domain, but not with other domain scores measuring executive and visuoperceptual functions, declarative verbal learning and memory, simple motor ability, or global neurocognitive function. Genotype shared approximately 11% of variance with Processing Speed and Attention scores, and approximately 2% of variance with Wisconsin Card Sorting Test scores.
  
  
  CONCLUSIONS
  The findings provide independent support for the hypothesis that the catechol-O-methyltransferase Val(158)Met polymorphism influences neurocognitive function in schizophrenia, and suggest that the functional effects may be expressed on measures of Processing Speed and Attention. This information may prompt reconsideration of the "prefrontal dopamine" hypothesis and invites examination of a broader range of effects in efforts to refine the neurocognitive phenotype that is most relevant to variation in catechol-O-methyltransferase expression.
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bilder
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Pál
authors.initials: P
authors.lastname: Czobor
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Xingqun
authors.initials: X
authors.lastname: Ni
authors.forename: Robert S
authors.initials: RS
authors.lastname: Goldman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hoptman
authors.forename: Brian
authors.initials: B
authors.lastname: Sheitman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Michal
authors.initials: M
authors.lastname: Kunz
authors.forename: Miranda
authors.initials: M
authors.lastname: Chakos
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001288:Attention; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002908:Chronic Disease; D003071:Cognition; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000201:enzymology* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D014633:Valine / Q000235:genetics*
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine