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 Patrick
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
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UR - http://www.scopus.com/inward/citedby.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 -