Background
Catechol-O-methyltransferase (COMT) val108/158met (rs4680) is thought to affect dopamine regulated prefrontal cortical activity during working
memory (WM) tasks, and to weakly increase risk for developing schizophrenia. Recently,
other single nucleotide polymorphisms (SNPs) across the gene have emerged as additional
risk factors for schizophrenia: namely rs737865, rs165599, and rs2097603. In a large sample, we examined whether these SNPs affect WM.
Methods
Schizophrenic probands (n = 325), their nonpsychotic siblings (n = 359), and normal control subjects (n = 330) completed tests of WM function. Data were analyzed with a series of mixed
model analyses of variance (ANOVAs).
Results
Val homozygotes performed most poorly on all conditions of the n-back, irrespective
of diagnosis. Additionally, there was a trend towards a disease-only val108/158met effect on a test of attentional set-shifting; val homozygote probands performed
most poorly. Significant or near-significant effects of rs737865 were found on all conditions of the n-back, with G homozygotes performing worst.
There also was a disease-only COMT rs737865 effect on the 0-back. None of the other SNPs showed main effects by themselves. A
haplotype constructed from promoter and val108/158met SNPs showed main effects on WM parameters, consistent with inverted U models of
dopamine signaling.
Conclusions
We extended earlier findings of a val108/158met effect on WM function, and suggest that combinations of alleles within COMT may
modulate the val108/158met effect in a nonlinear manner.
Key Words
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Article info
Publication history
Published online: August 20, 2007
Accepted:
March 14,
2007
Received in revised form:
March 5,
2007
Received:
August 10,
2006
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
