Effect of Catechol-O-methyltransferase Val158met Genotype on Attentional Control

Overview

Journal J Neurosci

Specialty Neurology

Date 2005 May 20

PMID 15901785

Citations 119

Authors

Giuseppe Blasi

Venkata S Mattay

Alessandro Bertolino

Brita Elvevag

Joseph H Callicott

Saumitra Das

Bhaskar S Kolachana

Michael F Egan

Terry E Goldberg

Daniel R Weinberger

Affiliations

Soon will be listed here.

Abstract

The cingulate cortex is richly innervated by dopaminergic projections and plays a critical role in attentional control (AC). Evidence indicates that dopamine enhances the neurophysiological signal-to-noise ratio and that dopaminergic tone in the frontal cortex is critically dependent on catechol-O-methyltransferase (COMT). A functional polymorphism (val158met) in the COMT gene accounts for some of the individual variability in executive function mediated by the dorsolateral prefrontal cortex. We explored the effect of this genetic polymorphism on cingulate engagement during a novel AC task. We found that the COMT val158met polymorphism also affects the function of the cingulate during AC. Individuals homozygous for the high-activity valine ("val") allele show greater activity and poorer performance than val/methionine ("met") heterozygotes, who in turn show greater activity and poorer performance than individuals homozygous for the low-activity met allele, and these effects are most evident at the highest demand for AC. These results indicate that met allele load and presumably enhanced dopaminergic tone improve the "efficiency" of local circuit processing within the cingulate cortex and thereby its function during AC.

Citing Articles

Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction.

Pignalosa F, Desiderio A, Mirra P, Nigro C, Perruolo G, Ulianich L Int J Mol Sci. 2021; 22(22).

PMID: 34830246 PMC: 8619146. DOI: 10.3390/ijms222212366.

The Interplay Between Prenatal Adversity, Offspring Dopaminergic Genes, and Early Parenting on Toddler Attentional Function.

Szekely E, Jolicoeur-Martineau A, Atkinson L, Levitan R, Steiner M, Lydon J Front Behav Neurosci. 2021; 15:701971.

PMID: 34413728 PMC: 8370126. DOI: 10.3389/fnbeh.2021.701971.

Membrane bound catechol-O-methytransferase is the dominant isoform for dopamine metabolism in PC12 cells and rat brain.

Su Y, DePasquale M, Liao G, Buchler I, Zhang G, Byers S Eur J Pharmacol. 2021; 896:173909.

PMID: 33503461 PMC: 7962326. DOI: 10.1016/j.ejphar.2021.173909.

Tolcapone Treatment for Cognitive and Behavioral Symptoms in Behavioral Variant Frontotemporal Dementia: A Placebo-Controlled Crossover Study.

Fremont R, Manoochehri M, Armstrong N, Mattay V, Apud J, Tierney M J Alzheimers Dis. 2020; 75(4):1391-1403.

PMID: 32444540 PMC: 10131251. DOI: 10.3233/JAD-191265.

Effect of Functional BDNF and COMT Polymorphisms on Symptoms and Regional Brain Volume in Frontotemporal Dementia and Corticobasal Syndrome.

Huey E, Fremont R, Manoochehri M, Gazes Y, Lee S, Cosentino S J Neuropsychiatry Clin Neurosci. 2020; 32(4):362-369.

PMID: 32397876 PMC: 7606216. DOI: 10.1176/appi.neuropsych.19100211.

References

Callicott J, Mattay V, Bertolino A, Finn K, Coppola R, Frank J . Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex. 1999; 9(1):20-6. DOI: 10.1093/cercor/9.1.20. View

Livak K . Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal. 1999; 14(5-6):143-9. DOI: 10.1016/s1050-3862(98)00019-9. View

Weinshilboum R, Otterness D, Szumlanski C . Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. Annu Rev Pharmacol Toxicol. 1999; 39:19-52. DOI: 10.1146/annurev.pharmtox.39.1.19. View

Karayiorgou M, Sobin C, Blundell M, Galke B, Malinova L, Goldberg P . Family-based association studies support a sexually dimorphic effect of COMT and MAOA on genetic susceptibility to obsessive-compulsive disorder. Biol Psychiatry. 1999; 45(9):1178-89. DOI: 10.1016/s0006-3223(98)00319-9. View

Rypma B, DEsposito M . The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences. Proc Natl Acad Sci U S A. 1999; 96(11):6558-63. PMC: 26921. DOI: 10.1073/pnas.96.11.6558. View

Friston K, Zarahn E, Josephs O, Henson R, Dale A . Stochastic designs in event-related fMRI. Neuroimage. 1999; 10(5):607-19. DOI: 10.1006/nimg.1999.0498. View

Mannisto P, Kaakkola S . Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 1999; 51(4):593-628. View

Botvinick M, Nystrom L, Fissell K, Carter C, Cohen J . Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature. 2000; 402(6758):179-81. DOI: 10.1038/46035. View

Carter C, MacDonald A, Botvinick M, Ross L, Stenger V, Noll D . Parsing executive processes: strategic vs. evaluative functions of the anterior cingulate cortex. Proc Natl Acad Sci U S A. 2000; 97(4):1944-8. PMC: 26541. DOI: 10.1073/pnas.97.4.1944. View

10.

MacDonald 3rd A, Cohen J, Stenger V, Carter C . Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science. 2000; 288(5472):1835-8. DOI: 10.1126/science.288.5472.1835. View

11.

Casey B, Thomas K, Welsh T, Badgaiyan R, Eccard C, Jennings J . Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. Proc Natl Acad Sci U S A. 2000; 97(15):8728-33. PMC: 27016. DOI: 10.1073/pnas.97.15.8728. View

12.

Callicott J, Bertolino A, Mattay V, Langheim F, Duyn J, Coppola R . Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex. 2000; 10(11):1078-92. DOI: 10.1093/cercor/10.11.1078. View

13.

Seamans J, Durstewitz D, Christie B, Stevens C, Sejnowski T . Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons. Proc Natl Acad Sci U S A. 2001; 98(1):301-6. PMC: 14585. DOI: 10.1073/pnas.98.1.301. View

14.

Seamans J, Gorelova N, Durstewitz D, Yang C . Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J Neurosci. 2001; 21(10):3628-38. PMC: 6762481. View

15.

Egan M, Goldberg T, Kolachana B, Callicott J, Mazzanti C, Straub R . Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001; 98(12):6917-22. PMC: 34453. DOI: 10.1073/pnas.111134598. View

16.

Paus T . Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nat Rev Neurosci. 2001; 2(6):417-24. DOI: 10.1038/35077500. View

17.

Weinberger D, Egan M, Bertolino A, Callicott J, Mattay V, Lipska B . Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry. 2001; 50(11):825-44. DOI: 10.1016/s0006-3223(01)01252-5. View

18.

Moron J, Brockington A, Wise R, Rocha B, Hope B . Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci. 2002; 22(2):389-95. PMC: 6758674. View

19.

Alsobrook 2nd J, Zohar A, Leboyer M, Chabane N, Ebstein R, Pauls D . Association between the COMT locus and obsessive-compulsive disorder in females but not males. Am J Med Genet. 2002; 114(1):116-20. DOI: 10.1002/ajmg.10040. View

20.

Malhotra A, Kestler L, Mazzanti C, Bates J, Goldberg T, Goldman D . A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry. 2002; 159(4):652-4. DOI: 10.1176/appi.ajp.159.4.652. View