Background
Increased variability of stimulus-induced prefrontal electromagnetic activity (“noise”)
has been associated with genetic risk for schizophrenia. On the basis of animal experiments
and computational models, we have predicted that this prefrontal “noise” phenotype
would be related to variation in prefrontal dopamine (DA) signaling, which itself
might be abnormal in schizophrenia. In the present study, the effect of a functional
single nucleotide polymorphism (val108/158met) within the catechol-O-methyltransferase (COMT) gene on prefrontal “noise” was examined, because the COMT
enzyme is involved in cortical synaptic dopamine metabolism and weakly predictive
of risk for schizophrenia.
Methods
A Caucasian sample comprising 112 unrelated normal subjects, 83 schizophrenic probands,
and 87 of their unaffected siblings was investigated, all of whom had measures of
prefrontal “noise” estimated from event-related electroencephalogram during an auditory
oddball task.
Results
The val108/158met genotype was significantly associated with prefrontal “noise”; homozygous Val-carriers
had greatest prefrontal “noise” values; odds ratio (OR) = 2.37 (95% confidence interval
[CI] 1.37–4.10), p = 003. The genotype-phenotype association was stronger when only considering male
subjects with an OR = 3.37 (95% CI: 1.63–6.98), p = 002.
Conclusions
The results suggest that COMT genotype impacts the level of prefrontal physiologic
“noise.”
Key Words
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Article info
Publication history
Published online: May 28, 2006
Accepted:
March 7,
2006
Received in revised form:
June 22,
2005
Received in revised form:
February 28,
2006
Received:
January 26,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
