title: Influence of kynurenine 3-monooxygenase (KMO) gene polymorphism on cognitive function in schizophrenia.
abstract: BACKGROUND
  Cognitive deficits compromise quality of life and productivity for individuals with schizophrenia and have no effective treatments. Preclinical data point to the kynurenine pathway of tryptophan metabolism as a potential target for pro-cognitive drug development. We have previously demonstrated association of a kynurenine 3-monooxygenase (KMO) gene variant with reduced KMO gene expression in postmortem schizophrenia cortex, and neurocognitive endophenotypic deficits in a clinical sample. KMO encodes kynurenine 3-monooxygenase (KMO), the rate-limiting microglial enzyme of cortical kynurenine metabolism. Aberration of the KMO gene might be the proximal cause of impaired cortical kynurenine metabolism observed in schizophrenia. However, the relationship between KMO variation and cognitive function in schizophrenia is unknown. This study examined the effects of the KMO rs2275163C>T C (risk) allele on cognitive function in schizophrenia.
  
  
  METHODS
  We examined the association of KMO polymorphisms with general neuropsychological performance and P50 gating in a sample of 150 schizophrenia and 95 healthy controls.
  
  
  RESULTS
  Consistent with our original report, the KMO rs2275163C>T C (risk) allele was associated with deficits in general neuropsychological performance, and this effect was more marked in schizophrenia compared with controls. Additionally, the C (Arg452) allele of the missense rs1053230C>T variant (KMO Arg452Cys) showed a trend effect on cognitive function. Neither variant affected P50 gating.
  
  
  CONCLUSIONS
  These data suggest that KMO variation influences a range of cognitive domains known to predict functional outcome. Extensive molecular characterization of this gene would elucidate its role in cognitive function with implications for vertical integration with basic discovery.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: iwonodi@mprc.umaryland.edu.
authors.forename: Ikwunga
authors.initials: I
authors.lastname: Wonodi
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: McMahon
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Nithin
authors.initials: N
authors.lastname: Krishna
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Liu
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Glassman
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003071:Cognition; D005071:Evoked Potentials; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D050601:Kynurenine 3-Monooxygenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D050601:Kynurenine 3-Monooxygenase
keywords: Cognition; Genetic association; KMO; Kynurenine; P50; Schizophrenia