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Cerebral Cortex Advance Access published online on July 29, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp132
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

Nancy A. Dennis1,2, Anna C. Need3, Kevin S. LaBar1, Sheena Waters-Metenier1, Elizabeth T. Cirulli3, James Kragel1, David B. Goldstein3 and Roberto Cabeza1

1 Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA, 2 Department of Psychology, The Pennsylvania State University, University Park, PA 16802, USA, 3 Center for Human Genome Variation, Institute for Genome Science and Policy, Duke University, Durham, NC 27708, USA

Address correspondence to Dr Nancy A. Dennis, PhD, Department of Psychology, The Pennsylvania State University, University Park, PA 16802, USA. Email: nad12{at}psu.edu.

The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496–1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

Key Words: COMT • fMRI • genetic neuroimaging • relational memory

Nancy A. Dennis and Anna C. Need contributed equally to this manuscript.


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