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Effect of COMT val158met genotype on cognition and personality

  • A.J. Sheldrick (a1), A. Krug (a1), V. Markov (a1), D. Leube (a1), T.M. Michel (a1), K. Zerres (a2), T. Eggermann (a2) and T. Kircher (a1)...

Abstract

The gene encoding catechol-O-methyltransferase (COMT), an enzyme which regulates prefrontal cortex dopamine, contains a common functional single nucleotide polymorphism (val158met, rs4680 G/A), which accounts for part of the interindividual variance in performance during working memory tasks and also predicts personality traits.

We examined the relationship between the val158met polymorphism and cognitive function as well as personality traits in 522 healthy individuals (mean age: 24.75 years, SD = 5.84, mean years of education: 15.59, SD = 2.65).

COMT val158met genotype was related in allele dosage fashion to performance in an executive function test, with the met/met carriers scoring highest. Subjects carrying the met/met genotype also scored higher in the disorganization domain of the SPQ-B personality inventory.

Consistent with evidence from previous studies, higher dopamine availability of the met/met genotype enhances prefrontally mediated executive function in healthy individuals.

Furthermore, we replicated findings from a recent study whereby the COMT genotype also predicts disorganized personality features.

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Corresponding author

*Corresponding author. Department of Psychiatry and Psychotherapy, University Clinic Aachen, Pauwelsstrasse 30, D-52074 Aachen, Nordrhein-Westphalen, Germany. Tel.: +49 (0)241 80 3; fax: +49 (0)80 82397. E-mail address: asheldrick@ukaachen.de (A.J. Sheldrick).

References

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[1]Aquilera, M.Barrantes-Vidal, N.Arias, B.Moya, J.Villa, H.Ibáñez, M.I.et al.Putative role of the COMT gene polymorphism (Val158Met) on verbal working memory functioning in a healthy population Am J Med Genet B Neuropsychiatr Genet. 2008
[2]Badner, J.A.Gershon, E.S.Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia Mol Psychiatry. 7 2002 405411
[3]Barnett, J.H.Jones, P.B.Robbins, T.W.Müller, U.Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls Mol Psychiatry. 12 2007 502509
[4]Bertocci, B.Miggiano, V.Da Prada, M.Dembic, Z.Lahm, H.W.Herbe, P.Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form Neurobiology. 88 1991 14161420
[5]Bilder, R.M.Volavka, J.Lachman, H.M.Grace, A.A.The catechol-O-methyltransferase polymorphism: relations to the tonic–phasic dopamine hypothesis and neuropsychiatric phenotypes Neuropsychopharmacology. 29 2004 19431961
[6]Bilder, R.M.Volavka, J.Czobor, P.Malhotra, A.K.Kennedy, J.L.Ni, X.et al.Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia Biol Psychiatry. 52 2002 701707
[7]Breier, A.Kestler, L.Adler, C.Elman, I.Wiesenfeld, N.Malhotra, A.et al.Dopamine D2 receptor density and personal detachment in healthy subjects Am J Psychiatry. 155 1998 14401442
[8]Brickenkamp, R.Der Aufmerksamkeits-Belastungstest d2 2002 Hogrefe Göttingen
[9]Bruder, G.E.Keilp, J.G.Xu, H.Shikhman, M.Schori, E.Gorman, J.M.et al.Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations Biol Psychiatry. 58 2005 901907
[10]Chen, J.Lipska, B.K.Halim, N.Ma, Q.D.Matsumoto, M.Melhem, S.et al.Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects of mRNA, protein and enzyme activity in postmortem human brain Am J Hum Genet. 75 2004 807821
[11]Costa, P.T.McCrae, R.R.Revised NEO personality inventory (NEO PI-R) and NEO Five Factor Inventory Professional Manual 1992 Psychological Assessement Resources Odessa, Fl.
[12]Daum, I.Graber, S.Schugens, M.M.Mayes, A.R.Memory dysfunction of the frontal type in normal ageing Neuroreport. 7 1996 26252628
[13]Egan, M.F.Goldberg, T.E.Kolachana, B.S.Callicott, J.H.Mazzanti, C.M.Straub, R.E.et al.Effect of COMT Val(108/158) Met genotype on frontal lobe function and risk for schizophrenia Proc Natl Acad Sci U S A. 98 2001 69176922
[14]Ehlis, A.C.Reif, A.Herrmann, M.J.Lesch, K.P.Fallgatter, A.J.Impact of catechol-O-methyltransferase on prefrontal brain functioning in schizophrenia spectrum disorders Neuropsychopharmacology. 32 2007 162170
[15]Ettinger, U.Kumari, V.Collier, D.A.Powell, J.Luzi, S.Michel, T.M.et al.Catechol-O-methyltransferase (COMT) Val158Met genotype is associated with BOLD response as a function of task characteristic Neuropsychopharmacology. 2008 Advance online publication
[16]Gold, J.M.Carpenter, C.Randolph, C.Goldberg, T.E.Weinberger, D.R.Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia Arch Gen Psychiatry. 54 1997 159165
[17]Goldberg, T.E.Egan, M.F.Gscheidle, T.Coppola, R.Weickert, T.Kolachana, B.S.et al.Executive subprocesses in working memory: relationship of catechol-O-methyltransferase Val158Met genotype and schizophrenia Arch Gen Psychiatry. 60 2003 889896
[18]Härting, C.Markowitsch, H.J.Neufeld, H.Calabrese, P.Deisinger, K.Wechlser Gedächtnis Test – Revidierte Fassung 2002 Hogrefe Göttingen
[19]Ho, B.-C.Wassink, T.H.O'Leary, D.S.Sheffield, V.C.Andreasen, N.C.Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow Mol Psychiatry. 10 2005 287298
[20]Joober, R.Rouleau, G.A.Lal, S.Dixon, M.O´Driscoll, G.Palmour, R.et al.Neuropsychological impairments in neuroleptic-responder vs. -nonresponder schizophrenic patients and healthy volunteers Schizophr Res. 53 2002 229238
[21]Laakso, A.Vilkman, H.Kajander, J.Bergman, J.Paranta, M.Solin, O.et al.Prediction of detached personality in healthy subjects by low dopamine transporter binding Am J Psychiatry. 157 2000 290292
[22]Laakso, A.Wallius, E.Kajander, J.Bergman, J.Eskola, O.Solin, O.et al.Personality traits and striatal dopamine synthesis capacity in healthy subjects Am J Psychiatry. 160 2003 904910
[23]Lachman, H.M.Papolos, D.F.Saito, T.Yu, Y.M.Szumlanski, C.L.Weinshilboum, R.M.Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychological disorders Pharmacogenetics. 6 1996 243250
[24]Lehrl, S.Der Mehrfachwahl-Wortschatz-Intelligenztest 2005 Hogrefe
[25]Lotta, T.Vidgren, J.Tilgmann, C.Ulmanen, I.Melén, K.Julkunen, I.et al.Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme Biochemistry. 34 1995 42024210
[26]Ma, X.Sun, J.Yao, J.Wang, Q.Hu, X.Deng, W.et al.A quantitative association study between schizotypal traits and COMT, PRODH and BDNF genes in a healthy Chinese population Psychiatry Res. 153 2007 715
[27]Malhotra, A.K.Kestler, L.J.Mazzanti, C.Bates, J.A.Goldberg, T.Goldman, D.A.Functional polymorphism in the COMT gene and performance on a test of prefrontal cognition Am J Psychiatry. 59 1992 652654
[28]Minzenberg, M.J.Xu, K.Mitropoulou, V.Harvey, P.D.Finch, T.Flory, J.D.et al.Catechol-O-methyltransferase VaI(158)Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups Psychiatr Genet. 16 2006 117124
[29]Morón, J.A.Brockington, A.Wise, R.Rocha, B.A.Hope, B.T.Dopamine uptake through the Norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines J Neurosci. 22 2001 389395
[30]Oldfield, R.C.The assessment and analysis of handedness: the Edinburgh inventory Neuropsychologia. 9 1971 97113
[31]Palmatier, M.A.Kang, M.Kidd, K.K.Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles Biol Psychiatry. 46 1999 567
[32]Pooley, E.C.Fineberg, N.Harrison, P.J.The met158 allele of catechol-O-methyltransferase (COMT) is associated with obsessive–compulsive disorder in men: case–control study and meta-analysis Mol Psychiatry. 12 2007 556561
[33]Raine, A.The SPQ: a scale for the assessment of schizotypical personality based on DSM-III-R criteria Schizophr Bull. 17 1991 556564
[34]Reitan, R.M.Wolfson, D.The Halstead-Reitan neuropsychological test battery: theory and clinical interpretation 1985 Neuropsychology Press Tucson
[35]Rosa, A.Peralta, V.Cuesta, M.J.Zarzuela, A.Serrano, F.Martínez-Larrea, A.et al.New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis Am J Psychiatry. 161 2004 11101112
[36]Schneier, F.R.Liebowitz, M.R.Abi-Dargham, A.Zea-Ponce, Y.Lin, S.-H.Laruelle, M.Low dopamine D2 receptor binding potential in social phobia Am J Psychiatry. 157 2000 457459
[37]Schürhoff, F.Szöke, A.Chevalier, F.Roy, I.Méary, A.Bellivier, F.et al.Schizotypal dimensions: an intermediate phenotype associated with the COMT high activity allele Am J Med Genet B Neuropsychiatr Genet. 144B 2007 6468
[38]Stefanis, N.C.Van Os, J.Avramopoulos, D.Smyrnis, N.Evdokimidis, I.Hantoumi, I.et al.Variation in catechol-O-methyltransferase val158 met genotype associated with schizotypy but not cognition: a population study in 543 young men Biol Psychiatry. 56 2004 510515
[39]Stefanis, N.C.Van Os, J.Avramopoulos, D.Smyrnis, N.Evdokimidis, I.Stefanis, C.N.Effect of COMT Val158Met polymorphism on the continuous performance test, identical pairs version: tuning rather than improving performance Am J Psychiatry. 162 2005 17521754
[40]Suhara, T.Yasuno, F.Sudo, Y.Yamamoto, M.Inoue, M.Okubo, Y.et al.Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking Neuroimage. 13 2001 891895
[41]Tan, H.Y.Chen, Q.Goldberg, T.E.Mattay, V.S.Meyer-Lindenberg, A.Weinberger, D.R.et al.Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal–striatal brain systems during arithmetic and temporal transformations in working memory J Neurosci. 27 2007 1339313401
[42]Wechsler, D.Wechsler memory scale: administration and scoring manual 3rd ed. 1997 The Psychological Corporation: Harcourt Brace & Co San Antonio
[43]Weinshilboum, R.M.Otterness, D.M.Szumlanski, C.L.Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase and histamine N-methyltransferase Annu Rev Pharmacol Toxicol. 39 1999 1952
[44]World Health Organization, The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research 1993 WHO Geneva

Keywords

Effect of COMT val158met genotype on cognition and personality

  • A.J. Sheldrick (a1), A. Krug (a1), V. Markov (a1), D. Leube (a1), T.M. Michel (a1), K. Zerres (a2), T. Eggermann (a2) and T. Kircher (a1)...

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Effect of COMT val158met genotype on cognition and personality

  • A.J. Sheldrick (a1), A. Krug (a1), V. Markov (a1), D. Leube (a1), T.M. Michel (a1), K. Zerres (a2), T. Eggermann (a2) and T. Kircher (a1)...
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