Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia.
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.
Bilder
Robert M
RM
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
Volavka
Jan
J
Czobor
Pál
P
Malhotra
Anil K
AK
Kennedy
James L
JL
Ni
Xingqun
X
Goldman
Robert S
RS
Hoptman
Matthew J
MJ
Sheitman
Brian
B
Lindenmayer
Jean-Pierre
JP
Citrome
Leslie
L
McEvoy
Joseph P
JP
Kunz
Michal
M
Chakos
Miranda
M
Cooper
Thomas B
TB
Lieberman
Jeffrey A
JA
D000328:Adult; D019943:Amino Acid Substitution; D001288:Attention; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002908:Chronic Disease; D003071:Cognition; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000201:enzymology* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D014633:Valine / Q000235:genetics*
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D004298:Dopamine