Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia

Robert M. Bilder, Jan Volavka, Pál Czobor, Anil K. Malhotra, James L. Kennedy, Xingqun Ni, Robert S. Goldman, Matthew J. Hoptman, Brian Sheitman, Jean Pierre Lindenmayer, Leslie Citrome, Joseph Patrick McEvoy, Michal Kunz, Miranda Chakos, Thomas B. Cooper, Jeffrey A. Lieberman

Research output: Contribution to journalArticle

280 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)701-707
Number of pages7
JournalBiological Psychiatry
Volume52
Issue number7
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Catechol O-Methyltransferase
Schizophrenia
Aptitude
Dopamine
Genotype
Verbal Learning
Executive Function
Exons
Alleles
Phenotype
Genes

Keywords

  • Attention
  • Catechol-O-methyltransferase (COMT)
  • Cognition
  • Genetics
  • Neuropsychology
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Bilder, R. M., Volavka, J., Czobor, P., Malhotra, A. K., Kennedy, J. L., Ni, X., ... Lieberman, J. A. (2002). Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia Biological Psychiatry, 52(7), 701-707. https://doi.org/10.1016/S0006-3223(02)01416-6

Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia . / Bilder, Robert M.; Volavka, Jan; Czobor, Pál; Malhotra, Anil K.; Kennedy, James L.; Ni, Xingqun; Goldman, Robert S.; Hoptman, Matthew J.; Sheitman, Brian; Lindenmayer, Jean Pierre; Citrome, Leslie; McEvoy, Joseph Patrick; Kunz, Michal; Chakos, Miranda; Cooper, Thomas B.; Lieberman, Jeffrey A.

In: Biological Psychiatry, Vol. 52, No. 7, 01.10.2002, p. 701-707.

Research output: Contribution to journalArticle

Bilder, RM, Volavka, J, Czobor, P, Malhotra, AK, Kennedy, JL, Ni, X, Goldman, RS, Hoptman, MJ, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, JP, Kunz, M, Chakos, M, Cooper, TB & Lieberman, JA 2002, ' Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia ', Biological Psychiatry, vol. 52, no. 7, pp. 701-707. https://doi.org/10.1016/S0006-3223(02)01416-6
Bilder, Robert M. ; Volavka, Jan ; Czobor, Pál ; Malhotra, Anil K. ; Kennedy, James L. ; Ni, Xingqun ; Goldman, Robert S. ; Hoptman, Matthew J. ; Sheitman, Brian ; Lindenmayer, Jean Pierre ; Citrome, Leslie ; McEvoy, Joseph Patrick ; Kunz, Michal ; Chakos, Miranda ; Cooper, Thomas B. ; Lieberman, Jeffrey A. / Neurocognitive correlates of the COMT Val 158 Met polymorphism in chronic schizophrenia In: Biological Psychiatry. 2002 ; Vol. 52, No. 7. pp. 701-707.
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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.",
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AU - Volavka, Jan

AU - Czobor, Pál

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AU - Kennedy, James L.

AU - Ni, Xingqun

AU - Goldman, Robert S.

AU - Hoptman, Matthew J.

AU - Sheitman, Brian

AU - Lindenmayer, Jean Pierre

AU - Citrome, Leslie

AU - McEvoy, Joseph Patrick

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