Catechol O-methyltransferase variants and cognitive performance in schizophrenia and bipolar disorder versus controls.
BACKGROUND
The gene encoding Catechol O-methyltransferase (COMT), a dopamine catabolic enzyme, is an important candidate gene in several psychiatric disorders. Several studies have shown an association between the functional Val(158)Met polymorphism and cognitive performance. However, the results have been inconsistent and there are few studies addressing other COMT single nucleotide polymorphisms (SNPs).


METHODS
We investigated SNPs across the whole COMT gene, including the Val(158)Met polymorphism, for a putative effect on working memory, executive function and IQ in 315 patients with schizophrenia or bipolar disorder and 340 healthy controls.


RESULTS
We replicated the association between the Val(158)Met variant and working memory performance, and found a significant interaction between this SNP and diagnosis, with patients with schizophrenia showing a specific, reduced performance on the 2-back test. Several other COMT SNPs were associated with different cognitive functions, but did not remain significant after controlling for multiple testing. We also found significant interaction effects between the SNP variants and gender.


CONCLUSIONS
The present study replicates earlier findings showing an association between the functional Val(158)Met polymorphism and working memory performance, with schizophrenia subjects particularly vulnerable. Furthermore, our findings suggest that other parts of the COMT gene seem to affect several related cognitive domains, which further support the notion that COMT is a modifier gene in prefrontal dopamine functioning.
Wirgenes
Katrine V
KV
Institute of Psychiatry, University of Oslo, Oslo, Norway.
Djurovic
Srdjan
S
Sundet
Kjetil
K
Agartz
Ingrid
I
Mattingsdal
Morten
M
Athanasiu
Lavinia
L
Melle
Ingrid
I
Andreassen
Ole A
OA
D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D009664:Norway / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000235:genetics; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine