Abstract
Catechol-O-methyl transferase (COMT) val108/158met polymorphism impacts on cortical dopamine levels and may influence functional magnetic resonance (fMRI) measures of task-related neuronal activity. Here, we investigate whether COMT genotype influences cortical activations, particularly prefrontal activations, by interrogating its effect across three tasks that have been associated with the dopaminergic system in a large cohort of healthy volunteers. A total of 50 participants (13 met/met, 23 val/met, and 14 val/val) successfully completed N-Back, Go-NoGo, and Tower of London fMRI tasks. Image analysis was performed using statistical parametric mapping. No significant relationships between COMT genotype groups and frontal lobe activations were observed for any contrast of the three tasks studied. However, the val/val group produced significantly greater deactivation of the right posterior cingulate cortex in two tasks: the Go-NoGo (NoGo vs Go deactivation contrast) and N-Back (2-back vs rest deactivation contrast). For the N-Back task, the modulated deactivation cluster was functionally connected to the precuneus, left middle occipital lobe, and cerebellum. These results do not support findings of prefrontal cortical modulation of activity with COMT genotype, but instead suggest that COMT val/val genotype can modulate the activity of the posterior cingulate and may indicate the potential network effects of COMT genotype on the default mode network.
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Acknowledgements
We thank Nick Craddock, Detelina Grozeva, and Jennifer Turner for their help and assistance with COMT genotyping. We also thank the radiographers and staff of the Cyclotron and MRI units, Hammersmith Hospital, London. The study was supported by a departmental core-funding grant from the Medical Research Council, UK.
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Dr Stokes and Dr Rhodes report no conflict of interest. Professor Grasby has served as an occasional consultant to GlaxoSmithKline, Merck, and Pfizer. Dr Mehta reports research grant support from Pfizer, GlaxoSmithKline, and Evotec Neurosciences.
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Stokes, P., Rhodes, R., Grasby, P. et al. The Effects of The COMT val108/158met Polymorphism on BOLD Activation During Working Memory, Planning, and Response Inhibition: A Role for The Posterior Cingulate Cortex?. Neuropsychopharmacol 36, 763–771 (2011). https://doi.org/10.1038/npp.2010.210
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DOI: https://doi.org/10.1038/npp.2010.210
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