Prefrontal electrophysiologic "noise" and catechol-O-methyltransferase genotype in schizophrenia.
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 (val(108/158)met) 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 val(108/158)met 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."
Winterer
Georg
G
Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Egan
Michael F
MF
Kolachana
Bhaskar S
BS
Goldberg
Terry E
TE
Coppola
Richard
R
Weinberger
Daniel R
DR
D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002394:Catechol O-Methyltransferase / Q000502:physiology*; D016001:Confidence Intervals; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009622:Noise; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012737:Sex Factors; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine