Abstract
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 × 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.
Keywords
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Article info
Publication history
Accepted:
November 27,
2002
Received in revised form:
November 12,
2002
Received:
July 31,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
