Neurocognitive correlates of the COMT Val¹⁵⁸Met polymorphism in chronic schizophrenia (2024)

Bilder, R. M., Volavka, J., Czobor, P., Malhotra, A. K., Kennedy, J. L., Ni, X., Goldman, R. S., Hoptman, M. J., Sheitman, B., Lindenmayer, J. P., Citrome, L., McEvoy, J. P., Kunz, M., Chakos, M., Cooper, T. B., & Lieberman, J. A. (2002). Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia. Biological Psychiatry, 52(7), 701-707. https://doi.org/10.1016/S0006-3223(02)01416-6

Bilder, Robert M. ; Volavka, Jan ; Czobor, Pál et al. / Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia. In: Biological Psychiatry. 2002 ; Vol. 52, No. 7. pp. 701-707.

@article{de5cfefd53374342886268df30b0236a,

title = "Neurocognitive correlates of the COMT Val158Met 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, Val158Met 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 Val158Met 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 Val158Met 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.",

keywords = "Attention, Catechol-O-methyltransferase (COMT), Cognition, Genetics, Neuropsychology, Schizophrenia",

author = "Bilder, {Robert M.} and Jan Volavka and P{\'a}l Czobor and Malhotra, {Anil K.} and Kennedy, {James L.} and Xingqun Ni and Goldman, {Robert S.} and Hoptman, {Matthew J.} and Brian Sheitman and Lindenmayer, {Jean Pierre} and Leslie Citrome and McEvoy, {Joseph P.} and Michal Kunz and Miranda Chakos and Cooper, {Thomas B.} and Lieberman, {Jeffrey A.}",

note = "Funding Information: National Institutes of Mental Health (NIMH) grant (R10 MH53550) provided the principal support for this project. Additional support was provided by the University of North Carolina-Mental Health and Neuroscience Clinical Research Center (MH MH33127); the Foundation of Hope, Raleigh North Carolina; and the Canadian Institutes for Health Research (MGP-15007). The authors thank Janssen Pharmaceutica Research Foundation; Eli Lilly and Company; Novartis Pharmaceuticals Corporation; and Merck and Co., Inc. for their generous gifts of medications. Eli Lilly and Company contributed supplemental funding. Linda Kline, RN, MS, CS was the chief coordinator of the entire project.",

year = "2002",

month = oct,

day = "1",

doi = "10.1016/S0006-3223(02)01416-6",

language = "English",

volume = "52",

pages = "701--707",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "7",

}

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 Val158Met polymorphism in chronic schizophrenia', Biological Psychiatry, vol. 52, no. 7, pp. 701-707. https://doi.org/10.1016/S0006-3223(02)01416-6

Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia. / Bilder, Robert M.; Volavka, Jan; Czobor, Pál et al.
In: Biological Psychiatry, Vol. 52, No. 7, 01.10.2002, p. 701-707.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia

AU - Bilder, Robert M.

AU - Volavka, Jan

AU - Czobor, Pál

AU - Malhotra, Anil K.

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 P.

AU - Kunz, Michal

AU - Chakos, Miranda

AU - Cooper, Thomas B.

AU - Lieberman, Jeffrey A.

N1 - Funding Information:National Institutes of Mental Health (NIMH) grant (R10 MH53550) provided the principal support for this project. Additional support was provided by the University of North Carolina-Mental Health and Neuroscience Clinical Research Center (MH MH33127); the Foundation of Hope, Raleigh North Carolina; and the Canadian Institutes for Health Research (MGP-15007). The authors thank Janssen Pharmaceutica Research Foundation; Eli Lilly and Company; Novartis Pharmaceuticals Corporation; and Merck and Co., Inc. for their generous gifts of medications. Eli Lilly and Company contributed supplemental funding. Linda Kline, RN, MS, CS was the chief coordinator of the entire project.

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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, Val158Met 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 Val158Met 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 Val158Met 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.

AB - 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, Val158Met 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 Val158Met 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 Val158Met 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.

KW - Attention

KW - Catechol-O-methyltransferase (COMT)

KW - Cognition

KW - Genetics

KW - Neuropsychology

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0036792151&partnerID=8YFLogxK

U2 - 10.1016/S0006-3223(02)01416-6

DO - 10.1016/S0006-3223(02)01416-6

M3 - Article

C2 - 12372660

AN - SCOPUS:0036792151

SN - 0006-3223

VL - 52

SP - 701

EP - 707

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 7

ER -

Bilder RM, Volavka J, Czobor P, Malhotra AK, Kennedy JL, Ni X et al. Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia. Biological Psychiatry. 2002 Oct 1;52(7):701-707. doi: 10.1016/S0006-3223(02)01416-6