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European Archives of Psychiatry and Clinical Neuroscience

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01-12-2009 | Original Paper

The effect of the COMT val¹⁵⁸met polymorphism on neural correlates of semantic verbal fluency

Authors: Axel Krug, Valentin Markov, Abigail Sheldrick, Sören Krach, Andreas Jansen, Klaus Zerres, Thomas Eggermann, Tony Stöcker, N. Jon Shah, Tilo Kircher

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 8/2009

Abstract

Variation in the val¹⁵⁸met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val¹⁵⁸met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val¹⁵⁸met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

Aguilera M, Barrantes-Vidal N, Arias B, Moya J, Villa H, Ibanez MI, Ruiperez MA, Ortet G, Fananas L (2008) Putative role of the COMT gene polymorphism (Val158Met) on verbal working memory functioning in a healthy population. Am J Med Genet B Neuropsychiatr Genet 147B:898–902CrossRefPubMed

Barnett JH, Scoriels L, Munafo MR (2008) Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry 64:137–144CrossRefPubMed

Basho S, Palmer ED, Rubio MA, Wulfeck B, Muller RA (2007) Effects of generation mode in fMRI adaptations of semantic fluency: paced production and overt speech. Neuropsychologia 45:1697–1706CrossRefPubMed

Bertolino A, Caforio G, Blasi G, De Candia M, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott JH, Mattay VS, Bellomo A, Scarabino T, Weinberger DR, Nardini M (2004) Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 161:1798–1805CrossRefPubMed

Bertolino A, Rubino V, Sambataro F, Blasi G, Latorre V, Fazio L, Caforio G, Petruzzella V, Kolachana B, Hariri A, Meyer-Lindenberg A, Nardini M, Weinberger DR, Scarabino T (2006) Prefrontal-hippocampal coupling during memory processing is modulated by COMT val158met genotype. Biol Psychiatry 60:1250–1258CrossRefPubMed

Blasi G, Mattay VS, Bertolino A, Elvevag B, Callicott JH, Das S, Kolachana BS, Egan MF, Goldberg TE, Weinberger DR (2005) Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci 25:5038–5045CrossRefPubMed

Braver TS, Bongiolatti SR (2002) The role of frontopolar cortex in subgoal processing during working memory. Neuroimage 15:523–536CrossRefPubMed

Burgess PW, Veitch E, y Costello A, Shallice T (2000) The cognitive and neuroanatomical correlates of multitasking. Neuropsychologia 38:848–863CrossRefPubMed

Burgess PW, Quayle A, Frith CD (2001) Brain regions involved in prospective memory as determined by positron emission tomography. Neuropsychologia 39:545–555CrossRefPubMed

10.

Cabeza R, Nyberg L (2000) Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 12:1–47CrossRefPubMed

11.

Christoff K, Gabrieli JDE (2000) The frontopolar cortex and human cognition: evidence for a rostrocaudal hierarchical organization within the human prefrontal cortex. Psychobiology 28:168–186

12.

Christoff K, Prabhakaran V, Dorfman J, Zhao Z, Kroger JK, Holyoak KJ, Gabrieli JD (2001) Rostrolateral prefrontal cortex involvement in relational integration during reasoning. Neuroimage 14:1136–1149CrossRefPubMed

13.

Drabant EM, Hariri AR, Meyer-Lindenberg A, Munoz KE, Mattay VS, Kolachana BS, Egan MF, Weinberger DR (2006) Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Arch Gen Psychiatry 63:1396–1406CrossRefPubMed

14.

Ehlis AC, Reif A, Herrmann MJ, Lesch KP, Fallgatter AJ (2007) Impact of catechol-O-methyltransferase on prefrontal brain functioning in schizophrenia spectrum disorders. Neuropsychopharmacology 32:162–170CrossRefPubMed

15.

Glatt SJ, Faraone SV, Tsuang MT (2003) Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case–control and family-based studies. Am J Psychiatry 160:469–476CrossRefPubMed

16.

Goldberg TE, Egan MF, Gscheidle T, Coppola R, Weickert T, Kolachana BS, Goldman D, Weinberger DR (2003) Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 60:889–896CrossRefPubMed

17.

Hirshorn EA, Thompson-Schill SL (2006) Role of the left inferior frontal gyrus in covert word retrieval: neural correlates of switching during verbal fluency. Neuropsychologia 44:2547–2557CrossRefPubMed

18.

Ho BC, Wassink TH, O’Leary DS, Sheffield VC, Andreasen NC (2005) Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow. Mol Psychiatry 10(229):287–298CrossRef

19.

Kircher T, Whitney C, Krings T, Huber W, Weis S (2008) Hippocampal dysfunction during free word association in male patients with schizophrenia. Schizophr Res 101:242–255CrossRefPubMed

20.

Koechlin E, Basso G, Pietrini P, Panzer S, Grafman J (1999) The role of the anterior prefrontal cortex in human cognition. Nature 399:148–151CrossRefPubMed

21.

Koechlin E, Corrado G, Pietrini P, Grafman J (2000) Dissociating the role of the medial and lateral anterior prefrontal cortex in human planning. Proc Natl Acad Sci USA 97:7651–7656CrossRefPubMed

22.

Kroger JK, Sabb FW, Fales CL, Bookheimer SY, Cohen MS, Holyoak KJ (2002) Recruitment of anterior dorsolateral prefrontal cortex in human reasoning: a parametric study of relational complexity. Cereb Cortex 12:477–485CrossRefPubMed

23.

Krug A, Markov V, Eggermann T, Krach S, Zerres K, Stocker T, Shah NJ, Schneider F, Nothen MM, Treutlein J, Rietschel M, Kircher T (2008) Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with differences in frontal brain activation in a working memory task in healthy individuals. Neuroimage 42:1569–1576CrossRefPubMed

24.

Lehrl S, Triebig G, Fischer B (1995) Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurol Scand 91:335–345CrossRefPubMed

25.

Leung HC, Gore JC, Goldman-Rakic PS (2005) Differential anterior prefrontal activation during the recognition stage of a spatial working memory task. Cereb Cortex 15:1742–1749CrossRefPubMed

26.

Maier W, Hofgen B, Zobel A, Rietschel M (2005) Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes? Eur Arch Psychiatry Clin Neurosci 255:159–166CrossRefPubMed

27.

Malhotra AK, Kestler LJ, Mazzanti C, Bates JA, Goldberg T, Goldman D (2002) A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry 159:652–654CrossRefPubMed

28.

Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA 100:6186–6191CrossRefPubMed

29.

McIntosh AM, Baig BJ, Hall J, Job D, Whalley HC, Lymer GK, Moorhead TW, Owens DG, Miller P, Porteous D, Lawrie SM, Johnstone EC (2007) Relationship of catechol-O-methyltransferase variants to brain structure and function in a population at high risk of psychosis. Biol Psychiatry 61:1127–1134CrossRefPubMed

30.

Meyer-Lindenberg A, Kohn PD, Kolachana B, Kippenhan S, McInerney-Leo A, Nussbaum R, Weinberger DR, Berman KF (2005) Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat Neurosci 8:594–596CrossRefPubMed

31.

Meyer-Lindenberg A, Nichols T, Callicott JH, Ding J, Kolachana B, Buckholtz J, Mattay VS, Egan M, Weinberger DR (2006) Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry 11:867–877, 797CrossRefPubMed

32.

Minzenberg MJ, Xu K, Mitropoulou V, Harvey PD, Finch T, Flory JD, New AS, Goldman D, Siever LJ (2006) Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups. Psychiatr Genet 16:117–124CrossRefPubMed

33.

Nunokawa A, Watanabe Y, Muratake T, Kaneko N, Koizumi M, Someya T (2007) No associations exist between five functional polymorphisms in the catechol-O-methyltransferase gene and schizophrenia in a Japanese population. Neurosci Res 58:291–296CrossRefPubMed

34.

Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113CrossRefPubMed

35.

Owen AM, McMillan KM, Laird AR, Bullmore E (2005) N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp 25:46–59CrossRefPubMed

36.

Ramnani N, Owen AM (2004) Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nat Rev Neurosci 5:184–194CrossRefPubMed

37.

Rasser PE, Johnston P, Lagopoulos J, Ward PB, Schall U, Thienel R, Bender S, Toga AW, Thompson PM (2005) Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching. Neuroimage 26:941–951CrossRefPubMed

38.

Rosa A, Peralta V, Cuesta MJ, Zarzuela A, Serrano F, Martinez-Larrea A, Fananas L (2004) New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis. Am J Psychiatry 161:1110–1112CrossRefPubMed

39.

Sanders AR, Duan J, Levinson DF, Shi J, He D, Hou C, Burrell GJ, Rice JP, Nertney DA, Olincy A, Rozic P, Vinogradov S, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Crowe RR, Cloninger CR, Martinez M, Gejman PV (2008) No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. Am J Psychiatry 165:497–506CrossRefPubMed

40.

Schneider F, Habel U, Reske M, Kellermann T, Stocker T, Shah NJ, Zilles K, Braus DF, Schmitt A, Schlosser R, Wagner M, Frommann I, Kircher T, Rapp A, Meisenzahl E, Ufer S, Ruhrmann S, Thienel R, Sauer H, Henn FA, Gaebel W (2007) Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study. Schizophr Res 89:198–210CrossRefPubMed

41.

Sheldrick AJ, Krug A, Markov V, Leube D, Michel TM, Zerres K, Eggermann T, Kircher T (2008) Effect of COMT val158met genotype on cognition and personality. Eur Psychiatry 23:385–389CrossRefPubMed

42.

Slotnick SD, Moo LR, Segal JB, Hart J Jr (2003) Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. Brain Res Cogn Brain Res 17:75–82CrossRefPubMed

43.

Stefanis NC, van Os J, Avramopoulos D, Smyrnis N, Evdokimidis I, Stefanis CN (2005) Effect of COMT Val158Met polymorphism on the continuous performance test, identical pairs version: tuning rather than improving performance. Am J Psychiatry 162:1752–1754CrossRefPubMed

44.

Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme, New York

45.

Tan HY, Chen Q, Goldberg TE, Mattay VS, Meyer-Lindenberg A, Weinberger DR, Callicott JH (2007) Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory. J Neurosci 27:13393–13401CrossRefPubMed

46.

Wagner AD, Desmond JE, Glover GH, Gabrieli JD (1998) Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes. Brain 121 (Pt 10):1985–2002

47.

Walter H, Vasic N, Hose A, Spitzer M, Wolf RC (2007) Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI. Neuroimage 35:1551–1561CrossRefPubMed

48.

Whitney C, Weis S, Krings T, Huber W, Kircher T (2009) Task-dependent Modulations of prefrontal and hippocampal activity during intrinsic word production. J Cogn Neurosci 4:697–712CrossRef

49.

Williams HJ, Glaser B, Williams NM, Norton N, Zammit S, MacGregor S, Kirov GK, Owen MJ, O’Donovan MC (2005) No association between schizophrenia and polymorphisms in COMT in two large samples. Am J Psychiatry 162:1736–1738CrossRefPubMed

50.

Wonodi I, Stine OC, Mitchell BD, Buchanan RW, Thaker GK (2003) Association between Val108/158 Met polymorphism of the COMT gene and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 120B:47–50CrossRefPubMed

Title: The effect of the COMT val158met polymorphism on neural correlates of semantic verbal fluency
Authors: Axel Krug
Valentin Markov
Abigail Sheldrick
Sören Krach
Andreas Jansen
Klaus Zerres
Thomas Eggermann
Tony Stöcker
N. Jon Shah
Tilo Kircher
Publication date: 01-12-2009
Publisher: D. Steinkopff-Verlag
Published in: European Archives of Psychiatry and Clinical Neuroscience / Issue 8/2009
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-009-0010-8

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The effect of the COMT val¹⁵⁸met polymorphism on neural correlates of semantic verbal fluency

Abstract

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Abstract

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