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
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Article info
Publication history
Accepted:
April 3,
2002
Received in revised form:
March 26,
2002
Received:
January 9,
2002
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
