Association of the G1947A COMT (Val(108/158)Met) gene polymorphism with prefrontal P300 during information processing.
BACKGROUND
A common functional polymorphism, G1947A, of the catechol-O-methyltransferase (COMT) enzyme has gained interest in schizophrenia research because of its critical involvement in cortical dopamine catabolism and frontal lobe function. An assumed mechanism of dopamine is the reduction of noise in prefrontal neural networks during information processing. Therefore, the hypothesis was tested whether a variation of the COMT genotype is associated with prefrontal noise, which is in part reflected by the frontal P300 amplitude. It was predicted that homozygous Met allele carriers have a lower frontal P300 amplitude.


METHODS
The P300 component (auditory oddball) was recorded in 49 schizophrenic patients and 170 healthy control subjects. Three single nucleotide polymorphisms (SNPs) of the COMT gene (G1947A, C1883G, and G1243A) were investigated.


RESULTS
We observed a significant effect of G1947A COMT genotype on frontal P300 amplitude, with evidence for a genotype x diagnosis interaction. Lower frontal P300 amplitudes occurred in homozygous carriers of the Met allele, particularly in schizophrenic patients.


CONCLUSIONS
The association of the frontal P300 amplitude with the G1947A COMT genotype further emphasizes the functional role of this SNP. As the finding was mainly observed in schizophrenic patients, this may indicate that additional factors are required to interact with COMT genotype to affect prefrontal function. The smaller frontal P300 amplitude in Met carriers suggests that the amount of noise in prefrontal neural networks during information processing might be in part under genetic control, which is mediated by dopamine.
Gallinat
Jürgen
J
Laboratory for Clinical Psychophysiology, Department of Psychiatry, Free University, Berlin, Germany and National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Bajbouj
Malek
M
Sander
Thomas
T
Schlattmann
Peter
P
Xu
Ke
K
Ferro
Erica F
EF
Goldman
David
D
Winterer
Georg
G
D000161:Acoustic Stimulation; D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D018913:Event-Related Potentials, P300; D005072:Evoked Potentials, Auditory; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000201:enzymology / Q000503:physiopathology*; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine