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The Journal of Neuroscience, September 2, 2009, 29(35):10855-10862; doi:10.1523/JNEUROSCI.1427-09.2009

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Behavioral/Systems/Cognitive
The Functional Val158Met Polymorphism of COMT Predicts Interindividual Differences in Brain {alpha} Oscillations in Young Men

Sereina Bodenmann,1 Thomas Rusterholz,1 Roland Dürr,1 Claudia Stoll,1 Valérie Bachmann,1,2 Eva Geissler,1 Karin Jaggi-Schwarz,1 and Hans-Peter Landolt1,2

1Institute of Pharmacology and Toxicology and 2Zürich Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland

Correspondence should be addressed to Dr. Hans-Peter Landolt, Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Email: landolt{at}pharma.uzh.ch

Individual patterns of the electroencephalogram (EEG) in wakefulness and sleep are among the most heritable traits in humans, yet distinct genetic and neurochemical mechanisms underlying EEG phenotypes are largely unknown. A functional polymorphism in the gene encoding catechol-O-methyltransferase (COMT), an enzyme playing an important role in cortical dopamine metabolism, causes a common substitution of methionine (Met) for valine (Val) at codon 158 of COMT protein. Val allele homozygotes exhibit higher COMT activity and lower dopaminergic signaling in prefrontal cortex than Met/Met homozygotes. Evidence suggests that this polymorphism affects executive functions in healthy individuals. We hypothesized that it also modulates functional aspects of EEG in wakefulness and sleep. EEG recordings were conducted twice on separate occasions in 10 Val/Val and 12 Met/Met allele carriers (all men) in wakefulness, and in baseline and recovery sleep before and after 40 h prolonged waking. During sleep deprivation, subjects received placebo and modafinil in randomized, cross-over manner. We show that the Val158Met polymorphism predicts stable and frequency-specific, interindividual variation in brain {alpha} oscillations. {alpha} peak frequency in wakefulness was 1.4 Hz slower in Val/Val genotype than in Met/Met genotype. Moreover, Val/Val allele carriers exhibited less 11–13 Hz activity than Met/Met homozygotes in wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep. This difference was resistant against the effects of sleep deprivation and modafinil. The data demonstrate that mechanisms involving COMT contribute to interindividual differences in brain {alpha} oscillations, which are functionally related to executive performance such as counting tendency on a random number generation task in young adults.


Received March 25, 2009; revised June 19, 2009; accepted July 12, 2009.

Correspondence should be addressed to Dr. Hans-Peter Landolt, Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Email: landolt{at}pharma.uzh.ch






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