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01-10-2009 | Biological Psychiatry - Original Article

Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans

Authors: Andrea M. Dlugos, Abraham A. Palmer, Harriet de Wit

Published in: Journal of Neural Transmission | Issue 10/2009

Abstract

Monoamine oxidase A and B (MAOA and MAOB) appear to be involved in the pathogenesis of Major Depression, and vulnerability of Major Depression is associated with personality traits relating to positive and negative affect. This study aimed to investigate associations between MAOA and MAOB polymorphisms and personality traits of positive and negative emotionality in healthy volunteers, to elucidate mechanisms underlying personality and the risk for depression. Healthy Caucasian volunteers (N = 150) completed the Multiphasic Personality Questionnaire (MPQ), which includes independent superfactors of Positive Emotionality and Negative Emotionality. Participants were genotyped for 8 MAOA and 12 MAOB single nucleotide polymorphisms (SNPs). Association analyses for both SNPs and haplotypes were performed using the permutation approach implemented in PLINK. Negative Emotionality was significantly associated with the two highly linked MAOB polymorphisms rs10521432 and rs6651806 (p < 0.002). Findings were extended in haplotype analyses. For MAOB the 4-SNP haplotype GACG formed from rs1799836, rs10521432, rs6651806 and rs590551 was significantly related to lower Negative Emotionality scores (p < 0.002). MAOA was not related to personality in this study. Our finding provides the first evidence that MAOB polymorphisms influence levels of negative emotionality in healthy human volunteers. If confirmed, these results could lead to a better understanding of personality traits and inter-individual susceptibility developing psychiatric disorders such as major depression.

Alia-Klein N, Goldstein RZ, Kriplani A, Logan J, Tomasi D, Williams B, Telang F, Shumay E, Biegon A, Craig IW, Henn F, Wang GJ, Volkow ND, Fowler JS (2008) Brain monoamine oxidase A activity predicts trait aggression. J Neurosci 28:5099–5104PubMedCrossRef

American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. Washington, DC

Barratt ES (1965) Factor analysis of some psychometric measures of impulsiveness and anxiety. Psychol Rep 16:547–554PubMed

Barratt ES (1994) Impulsiveness and aggression. In: Monahan J, Steadman HJ (eds) Violence and mental disorder: developments in risk assessment. University of Chicago, pp 61–79

Biederman J, Kim JW, Doyle AE, Mick E, Fagerness J, Smoller JW, Faraone SV (2008) Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study. Am J Med Genet B Neuropsychiatr Genet 147B:1511–1518PubMedCrossRef

Brummet BH, Boyle SH, Siegler IC, Kuhn CM, Surwitt RS, Garrett ME, Collins A, Ashley-Koch A, Williams RB (2008) HPA axis function in male caregivers: effect of the monoamine oxidase-A gene promoter (MAOA-uVNTR). Biol Psychol 79:250–255CrossRef

Buchsbaum MS, Haier RJ, Murphy DL (1977) Suicide attempts, platelet monoamine oxidase and average evoked response. Acta Psychiatr Scand 56:57–68CrossRef

Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854PubMedCrossRef

Cataldo MG, Nobile M, Lorusso ML, Battaglia M, Molteni M (2005) Impulsivity in depressed children and adolescents: a comparison between behavioral and neuropsychological data. Psychiatry Res 136:123–133PubMedCrossRef

Church AT, Burke PJ (1994) Exploratory and confirmatory tests of the big five and Tellegen’s three- and four-dimensional models. J Pers Soc Psychol 66:93–114PubMedCrossRef

Clark LA, Watson D, Mineka S (1994) Temperament, personality, and the mood and anxiety disorders. J Abnorm Psychol 103:103–116PubMedCrossRef

Cloninger CR (1987) A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry 44:573–588PubMed

Comings DE, Muhleman D, Gade R, Johnson P, Verde R, Saucier G, MacMurray G (1997) Cannabinoid receptor gene (CNR1) association with i.v. drug use. Mol Psychiatry 2:161–168PubMedCrossRef

Costa PT Jr, McCrae RR (1992) Revised NEO Personality Inventory (NEO-PI-R) an NEO Five Factor Inventory (NEOFFI) professional manual. Psychological Assessment Resources, Inc, Odessa

Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, Nöthen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP (1999) Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 8:621–624PubMedCrossRef

Derogatis L (1983) SCL-90-R Manual II. Clinical Psychometric Research, Towson

Dlugos A, Freitag C, Hohoff C, McDonald J, Cook EH, Deckert J, de Wit H (2007) Norepinephrine transporter gene variation modulates acute response to d-amphetamine. Biol Psychiatry 61:1296–1305PubMedCrossRef

Du L, Faludi G, Pakovits M, Sotonyi P, Bakish D, Hrdina PD (2002) High activity-related allele of MAO-A gene associated with depressed suicide in males. NeuroReport 13:1195–1198PubMedCrossRef

Fossati A, DiCeglie A, Acquarini E, Barratt ES (2001) Psychometric properties of an Italian version of the Barratt Impulsiveness Scale-11 (BIS-11) in nonclinical subjects. J Clin Psychol 57:815–828PubMedCrossRef

Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Shea C, Schlyer D, Wolf AP, Warner D, Zezulkova I, Cilento R (1996) Inhibition of monoamine oxidase B in the brains of smokers. Nature 379:733–736PubMedCrossRef

Fowler JS, Wang GJ, Volkow ND, Franceschi D, Logan J, Pappas N, Shea C, MacGregor RR, Garza V (2000) Maintenance of brain monoamine oxidase B inhibition in smokers after overnight cigarette abstinence. Am J Psychiatry 157:1864–1866PubMedCrossRef

Frank E, Kupfer DJ, Jacob M, Jarrett D (1987) Personality features and response to acute treatment in recurrent depression. J Pers Disord 1:14–26

Gao X, Scott WK, Wang G, Mayhew G, Li YJ, Vance JM, Martin ER (2008) Gene-gene interaction between FGF20 and MAOB in Parkinson disease. Ann Hum Genet 72:157–162PubMedCrossRef

Gokturk C, Schultze S, Nilsson KW, von Knorring L, Oreland L, Hallman J (2008) Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism. Arch Womens Ment Health 11:347–355PubMedCrossRef

Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, Karoum F, Gal J, Shih JC (1997) Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet 17:206–210PubMedCrossRef

Guerrera RJ (1990) Some biological and behavioural features with clinical personality types. J Nerv Ment Dis 178:556–566CrossRef

Hirschfeld RMA, Klerman GL, Lavori P, Keller M, Griffith P, Coryell W (1989) Premorbid personality assessments of first onset of major depression. Arch Gen Psychiatry 46:345–350PubMed

Hodgkinson CA, Yuan Q, Xu K, Shen PH, Heinz E, Lobos EA, Binder EB, Cubells J, Ehlers CL, Gelernter J, Mann J, Riley B, Roy A, Tabakoff B, Todd RD, Zhou Z, Goldman D (2008) Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol 43:505–515PubMed

Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, de Wit H (2005) Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. Am J Med Genet B Neuropsychiatr Genet 139B:42–44PubMedCrossRef

Holahan CJ, Moos RH (1991) Life stressors, personal and social resources, and depression. A 4-year structural model. J Abnorm Psychol 100:31–38PubMedCrossRef

Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: diazepam. Psychopharmacology (Berl) 71:269–273CrossRef

Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17:1285–1297PubMedCrossRef

Katon W, Lin E, Von Korff M, Bush T, Walker E, Simon G, Robinson P (1994) The predictors of persistence of depression in primary care. J Affect Disord 31:81–90PubMedCrossRef

Kersting A, Kroker K, Horstmann J, Baune BT, Hohoff C, Mortensen LS, Neumann LC, Arolt V, Domschke K (2007) Association of MAO-A variant with complicated grief in major depression. Neuropsychobiol 56:191–196CrossRef

Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv Biochem Psychopharmacol 5:393–408PubMed

Lenders JW, Eisenhofer G, Abeling NG, Berger W, Murphy DL, Konings CH, Wagemakers LM, Kopin IJ, Karoum F, van Gennip AH, Brunner HG (1996) Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J Clin Invest 97:1010–1019PubMedCrossRef

Lesch KR, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Mueller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotoin transporter-gene regulatory region. Science 274:1527–1531PubMedCrossRef

Li J, Wang Y, Hu S, Zhou R, Yu X, Wang B, Guan L, Yang L, Zhang F, Faraone SV (2008) The monoamine oxidase B gene exhibits significant association to ADHD. Am J Med Genet B Neuropsychiatr Genet 147:370–374PubMed

Lin S, Jiang S, Wu X, Qian Y, Wang D, Tang G, Gu N (2000) Association analysis between mood disorder and monoamine oxidase gene. Am J Med Genet 96:12–14PubMedCrossRef

Lott DC, Kim S, Cook EH Jr, de Wit H (2005) Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology 30:602–609PubMedCrossRef

Lott DC, Kim SJ, Cook EH, de Wit H (2006) Serotonin transporter genotype and acute subjective response to amphetamine. Am J Addict 15:327–335PubMedCrossRef

Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 95:9–23PubMedCrossRef

Manuck SB, Flory JD, Muldoon MF, Ferrell RE (2002) Central nervous system serotonergic responsivity and aggressive disposition in men. Physiol Behav 77:705–709PubMedCrossRef

Meltzer HY, Arora RC (1986) Platelet markers of suicidality. Ann N Y Acad Sci 487:271–280PubMedCrossRef

Murphy DL, Wright C, Buchsbaum MS, Nichols A, Costa JL, Wyatt RJ (1976) Platelet and plasma amine oxidase activity in 680 normals:sex and age differences and stability over time. Biochem Med 16:254–265CrossRef

Patrick CJ, Curtin JJ, Tellegen A (2002) Development and validation of a brief form of the Multidimensional Personality Questionnaire. Psychol Assess 14:150–1563PubMedCrossRef

Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt impulsiveness scale. J Clin Psychol 51:768–774PubMedCrossRef

Pedersen NL, Oreland L, Reynolds C, McClearn GE (1993) Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together. Psychiatry Res 46:239–251PubMedCrossRef

Pletscher A (1991) The discovery of antidepressants: a winding path. Experientia 47:4–8PubMedCrossRef

Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959PubMed

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81

Reif A, Lesch KP (2003) Toward a molecular architecture of personality. Behav Brain Res 139:1–20PubMedCrossRef

Ribasés M, Ramos-Quiroga JA, Hervás A, Bosch R, Bielsa A, Gastaminza X, Artigas J, Rodriguez-Ben S, Estivill X, Casas M, Cormand B, Bayés M (2009) Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry 14:71–85PubMedCrossRef

Rivera M, Gutiérrez B, Molina E, Torres-González F, Bellón JA, Moreno-Küstner B, King M, Nazareth I, Martínez-González LJ, Martínez-Espín E, Muñoz-García MM, Motrico E, Martínez-Cañavate T, Lorente JA, Luna JD, Cervilla JA (2009) High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample. Am J Med Genet B Neuropsychiatr Genet 150B:395–402PubMedCrossRef

Roberts RL, Luty SE, Mulder RT, Joyce PR, Kennedy MA (2004) Association between cytochrome P450 2D6 genotype and harm avoidance. Am J Med Genet B Neuropsychiatr Genet 127B:90–93PubMedCrossRef

Roggenbach J, Müller-Oerlinghausen B, Franke L, Uebelhack R, Blank S, Ahrens B (2007) Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects. J Neural Transm 114:479–487PubMedCrossRef

Roohi J, Devincent CJ, Hatchwell E, Gadow KD (2009) Association of a monoamine oxidase-A gene promoter polymorphism with ADHD and anxiety in boys with autism spectrum disorder. J Autism Dev Disord 39:67–74PubMedCrossRef

Ruchkin VV, Koposov RA, af Klinteberg B, Oreland L, Grigorenko EL (2005) Platelet MAO-B, personality, and psychopathology. J Abnorm Psychol 114:477–482PubMedCrossRef

Selzer ML (1971) The Michigan alcoholism screening test: the quest for a new diagnostic instrument. Am J Psychiatry 127:1653–1658PubMed

Shih JC, Chen K, Riddl MJ (1999) Role of MAO A and B in neurotransmitter metabolism and behavior. Pol J Pharmacol 51:25–29PubMed

Tadić A, Rujescu D, Müller MJ, Kohnen R, Stassen HH, Dahmen N, Szegedi A (2007) A monoamine oxidase B gene variant and short-term antidepressant treatment response. Prog Neuropsychopharmacol Biol Psychiatry 31:1370–1377PubMedCrossRef

Takahashi T, Oono H, Inoue T, Boku S, Kako Y, Kitaichi Y, Kusumi I, Masui T, Nakagawa S, Suzuki K, Tanaka T, Koyama T, Radford MH (2008) Depressive patients are more impulsive and inconsistent in intertemporal choice behavior for monetary gain and loss than healthy subjects-an analysis based on Tsallis’ statistics. Neuro Endocrinol Lett 29:351–358PubMed

Tellegen A (1985) Structures of mood and personality and their relevance to assessing anxiety, with an emphasis on self-report. In: Tuma AH, Maser JD (eds) Anxiety and the anxiety disorders. Hillsdale, New Jersey, pp 681–706

Tellegen A, Lykken DT, Bouchard TJ Jr, Wilcox KJ, Segal NL, Rich S (1988) Personality similarity in twins reared apart and together. J Pers Soc Psychol 54:1031–1039PubMedCrossRef

Veenstra-VanderWeele J, Qaadir A, Palmer AA, Cook EH Jr, de Wit H (2006) Association between the casein kinase 1 epsilon gene region and subjective response to D-amphetamine. Neuropsychopharmacology 31:1056–1063PubMedCrossRef

von Knorring AL, Hallmann J, von Knoring L, Oreland L (1991) Platelet monoamine oxidase activity in type 1 and type 2 alcoholism. Alcohol Alcohol 26:409–416

Watson D, Clark LA (1984) Negative affectivity: the disposition to experience aversive emotional states. Psychol Bull 96:465–490PubMedCrossRef

Weissman MM, Bland R, Joyce PR, Newman S, Wells JE, Wittchen HU (1993) Sex differences in rates of depression: cross-national perspectives. J Affect Disord 29:77–84PubMedCrossRef

Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lépine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK (1996) Cross-national epidemiology of major depression and bipolar disorder. JAMA 276:293–299PubMedCrossRef

Wong WK, Ou XM, Chen K, Shih JC (2002) Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. J Biol Chem 277:22222–22230PubMedCrossRef

Youdim MB, Bakhle YS (2006) Monoamine oxidase: isoforms and inhibitors in Parkinson’s disease and depressive illness. J Pharmacol 147(Suppl 1):287–296

Zhu QS, Chen K, Shih JC (1994) Bidirectional promoter of human monoamine oxidase A (MAO A) controlled by transcription factor Sp1. J Neurosci 14:7393–7403PubMed

Zisook S (1985) A clinical overview of monoamine oxidase inhibitors. Psychosomatics 26:240–246PubMed

Title: Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans
Authors: Andrea M. Dlugos
Abraham A. Palmer
Harriet de Wit
Publication date: 01-10-2009
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 10/2009
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-009-0281-2

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Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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