title: Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.
abstract: OBJECTIVE
  Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role.
  
  
  METHODS
  We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs.
  
  
  RESULTS
  We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients.
  
  
  CONCLUSIONS
  These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Camila T
authors.initials: CT
authors.lastname: Matsuzaka
authors.affiliation: Departamento de Saúde Coletiva, Faculdade de Medicina do ABC (FMABC), Santo André, SP, Brazil.
authors.forename: Denise
authors.initials: D
authors.lastname: Christofolini
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.|Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Ota
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.|Departamento de Psicologia Educacional, Centro Universitário Fundação Instituto de Ensino para Osasco (UNIFIEO), Osasco, SP, Brazil.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Berberian
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: Departamento de Psicobiologia, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Diego R
authors.initials: DR
authors.lastname: Mazzotti
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.|Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Leticia M
authors.initials: LM
authors.lastname: Spindola
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.|Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Moretti
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Marilia A C
authors.initials: MAC
authors.lastname: Smith
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Melaragno
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.|Disciplina de Genética, Departamento de Morfologia e Genética, UNIFESP, São Paulo, SP, Brazil.
authors.forename: Sintia I
authors.initials: SI
authors.lastname: Belangero
authors.affiliation: Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.|Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), UNIFESP, São Paulo, SP, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Bressan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009483:Neuropsychological Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002394:Catechol O-Methyltransferase