title: COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation.
abstract: BACKGROUND
  Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val(158)Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder.
  
  
  METHODS
  We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val(158)Met polymorphism and both neuropsychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence.
  
  
  RESULTS
  A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endophenotype. It is possible that the COMT Val(158)Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances.
  
  
  CONCLUSIONS
  The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them.
  
  
  CONCLUSIONS
  This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.
authors.affiliation: Section of Psychiatry, University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ira
authors.forename: Martina
authors.initials: M
authors.lastname: Zanoni
authors.forename: Mirella
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
authors.forename: Sarah
authors.initials: S
authors.lastname: Tosato
mesh_terms: D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D058068:Endophenotypes; D005625:Frontal Lobe / Q000473:pathology* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011597:Psychomotor Performance; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000473:pathology* / Q000503:physiopathology
chemical_list: D002394:Catechol O-Methyltransferase