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European Archives of Psychiatry and Clinical Neuroscience

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01-08-2013 | Original Paper

MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls

Authors: Niki Antypa, Ina Giegling, Raffaella Calati, Barbara Schneider, Annette M. Hartmann, Marion Friedl, Bettina Konte, Loredana Lia, Diana De Ronchi, Alessandro Serretti, Dan Rujescu

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 5/2013

Abstract

MAOA and, to a lesser extent, MAOB polymorphisms have been related to aggression traits and suicidality. We aimed to investigate the role of MAOA and MAOB in suicidal versus non-suicidal participants and interactions between genetic variation and suicidal status on aggression and anger-related traits. The sample was composed of three groups: one group of suicide attempters (n = 171, males 35.1 %), one group of suicide completers (n = 90, males 57.8 %) and a healthy control group (n = 317, males 43.8 %). We examined the following markers: MAOA rs909525, rs6323, and rs2064070, and MAOB rs1799836. Anger traits were measured with the state-trait anger expression inventory (STAXI) and aggression traits with the questionnaire for measuring factors of aggression (FAF). Associations were separately examined for males and females. Variation in the three MAOA variants was associated with higher levels of anger expressed outwards (STAXI “anger-out” subscale) in male suicidal patients compared to controls (p < 0.001). In females, the C allele of rs6323 showed higher scores on the same subscale (“anger out”) (p = 0.002). Allele frequencies of the MAOA rs909525 were associated with suicidality (p < 0.007). Our findings show an association between genetic variation in three polymorphisms of the MAOA and anger traits in suicidal males and one replication for the functional variant rs6323 in females. This relationship was stronger than a direct genetic association with suicide status. Future studies incorporating endophenotypic measures of anger and aggression in suicidal participants are warranted.

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Antypa N, Van der Does AJ, Penninx BW (2009) Cognitive reactivity: investigation of a potentially treatable marker of suicide risk in depression. J Affect Disord 122:46–52

Baud P (2005) Personality traits as intermediary phenotypes in suicidal behavior: genetic issues. Am J Med Genet C Semin Med Genet 133C:34–42PubMedCrossRef

Bertolote JM, Fleischmann A (2005) Suicidal behavior prevention: WHO perspectives on research. Am J Med Genet C Semin Med Genet 133C:8–12PubMedCrossRef

Bertolote JM, Fleischmann A, De Leo D, Bolhari J, Botega N, De Silva D, Tran Thi Thanh H, Phillips M, Schlebusch L, Varnik A, Vijayakumar L, Wasserman D (2005) Suicide attempts, plans, and ideation in culturally diverse sites: the WHO SUPRE-MISS community survey. Psychol Med 35:1457–1465PubMedCrossRef

Bondy B, Buettner A, Zill P (2006) Genetics of suicide. Mol Psychiatry 11:336–351PubMedCrossRef

Brent DA, Bridge J, Johnson BA, Connolly J (1996) Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch Gen Psychiatry 53:1145–1152PubMedCrossRef

Brent DA, Mann JJ (2005) Family genetic studies, suicide, and suicidal behavior. Am J Med Genet C Semin Med Genet 133C:13–24PubMedCrossRef

Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262:578–580PubMedCrossRef

Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Muller U, Aguet M, Babinet C, Shih JC et al (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 268:1763–1766PubMedCrossRef

10.

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

11.

Cates DS, Houston BK, Vavak CR, Crawford MH, Uttley M (1993) Heritability of hostility-related emotions, attitudes, and behaviors. J Behav Med 16:237–256PubMedCrossRef

12.

Courtet P, Gottesman, II, Jollant F, Gould TD (2011) The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies? Transl Psychiatry 1–7

13.

Courtet P, Jollant F, Buresi C, Castelnau D, Mouthon D, Malafosse A (2005) The monoamine oxidase A gene may influence the means used in suicide attempts. Psychiatr Genet 15:189–193PubMedCrossRef

14.

Dlugos AM, Palmer AA, de Wit H (2009) Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans. J Neural Transm 116:1323–1334PubMedCrossRef

15.

Du L, Faludi G, Palkovits 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

16.

Erdfelder E, Faul F, Buchner A (1996) Gpower: a general power analysis program. Behav Res Methods Instrum Comput 28:1–11CrossRef

17.

First MB, Spitzer RL, Gibbon M, Williams BW (1995) Structured clinical interview for DSM-IV axis-I disorders—patient edition (SCID- I/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York, NY

18.

First MB, Spitzer RL, Gibbon M, Williams BW, Benjamin L (1990) Structured clinical interview for DSM-IV axis II personality disorders (SCID-II). Biometrics Research Department, New York State Psychiatric Institute, New York, NY

19.

Foley DL, Eaves LJ, Wormley B, Silberg JL, Maes HH, Kuhn J, Riley B (2004) Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Arch Gen Psychiatry 61:738–744PubMedCrossRef

20.

Frazzetto G, Di Lorenzo G, Carola V, Proietti L, Sokolowska E, Siracusano A, Gross C, Troisi A (2007) Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype. PLoS One 2:e486PubMedCrossRef

21.

Giegling I, Olgiati P, Hartmann AM, Calati R, Moller HJ, Rujescu D, Serretti A (2009) Personality and attempted suicide. Analysis of anger, aggression and impulsivity. J Psychiatr Res 43:1262–1271PubMedCrossRef

22.

Giegling I, Rujescu D, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, De Ronchi D, Moller HJ, Serretti A (2007) Tachykinin receptor 1 variants associated with aggression in suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 144B:757–761PubMedCrossRef

23.

Guo G, Ou XM, Roettger M, Shih JC (2008) The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity. Eur J Hum Genet 16:626–634PubMedCrossRef

24.

Hampel R, Selg H (1975) FAF-Fragebogen zur Erfassung von Aggressivitatsfaktoren. Hogrefe Verlag fur Psychologie, Gottingen

25.

Hasler R, Perroud N, Baud P, Olie E, Guillaume S, Malafosse A, Courtet P (2012) CREB1 modulates the influence of childhood sexual abuse on adult’s anger traits. Genes Brain Behav 11:720–726

26.

Hawton K, van Heeringen K (2009) Suicide. Lancet 373:1372–1381PubMedCrossRef

27.

Hollander E (1999) Managing aggressive behavior in patients with obsessive-compulsive disorder and borderline personality disorder. J Clin Psychiatry 60(Suppl 15):38–44PubMed

28.

Hotamisligil GS, Breakefield XO (1991) Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet 49:383–392PubMed

29.

Hung CF, Lung FW, Hung TH, Chong MY, Wu CK, Wen JK, Lin PY (2011) Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis. J Affect Disord 136:643–649PubMedCrossRef

30.

Jansson M, McCarthy S, Sullivan PF, Dickman P, Andersson B, Oreland L, Schalling M, Pedersen NL (2005) MAOA haplotype associated with thrombocyte-MAO activity. BMC Genet 6:46PubMedCrossRef

31.

Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE (2006) MAOA, maltreatment, and gene-environment interaction predicting children’s mental health: new evidence and a meta-analysis. Mol Psychiatry 11:903–913PubMedCrossRef

32.

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

33.

Mann JJ (2003) Neurobiology of suicidal behaviour. Nat Rev Neurosci 4:819–828PubMedCrossRef

34.

Mann JJ, Waternaux C, Haas GL, Malone KM (1999) Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 156:181–189PubMed

35.

Manuck SB, Flory JD, Ferrell RE, Dent KM, Mann JJ, Muldoon MF (1999) Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biol Psychiatry 45:603–614PubMedCrossRef

36.

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

37.

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

38.

Moller-Leimkuhler AM (2003) The gender gap in suicide and premature death or: why are men so vulnerable? Eur Arch Psychiatry Clin Neurosci 253:1–8PubMedCrossRef

39.

Oreland L, Nilsson K, Damberg M, Hallman J (2007) Monoamine oxidases: activities, genotypes and the shaping of behaviour. J Neural Transm 114:817–822PubMedCrossRef

40.

Pavlov KA, Chistiakov DA, Chekhonin VP (2012) Genetic determinants of aggression and impulsivity in humans. J Appl Genet 53:61–82PubMedCrossRef

41.

Pierce DW (1981) The predictive validation of a suicide intent scale: a five year follow-up. Br J Psychiatry 139:391–396PubMedCrossRef

42.

Pompili M, Serafini G, Innamorati M, Moller-Leimkuhler AM, Giupponi G, Girardi P, Tatarelli R, Lester D (2010) The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention. Eur Arch Psychiatry Clin Neurosci 260:583–600PubMedCrossRef

43.

Qiu HT, Meng HQ, Song C, Xiu MH, da Chen C, Zhu FY, Wu GY, Kosten TA, Kosten TR, Zhang XY (2009) Association between monoamine oxidase (MAO)-A gene variants and schizophrenia in a Chinese population. Brain Res 1287:67–73PubMedCrossRef

44.

Raj YP (2004) Psychopharmacology of borderline personality disorder. Curr Psychiatry Rep 6:225–231PubMedCrossRef

45.

Rujescu D, Giegling I (2010) The genetics of neurosystems in mental ill-health and suicidality: beyond serotonin. Eur Psychiatry 25:272–274PubMedCrossRef

46.

Rujescu D, Giegling I, Bondy B, Gietl A, Zill P, Moller HJ (2002) Association of anger-related traits with SNPs in the TPH gene. Mol Psychiatry 7:1023–1029PubMedCrossRef

47.

Rujescu D, Giegling I, Gietl A, Hartmann AM, Moller HJ (2003) A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits. Biol Psychiatry 54:34–39PubMedCrossRef

48.

Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, Serretti A (2008) NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits. Am J Med Genet B Neuropsychiatr Genet 147B:42–48PubMedCrossRef

49.

Rutz W, von Knorring L, Pihlgren H, Rihmer Z, Walinder J (1995) Prevention of male suicides: lessons from Gotland study. Lancet 345:524PubMedCrossRef

50.

Schwenkmezger P, Hodapp V (1991) A questionnaire for assessing anger and expression of anger. Z Klin Psychol Psychopathol Psychother 39:63–68PubMed

51.

Scott AL, Bortolato M, Chen K, Shih JC (2008) Novel monoamine oxidase A knockout mice with human-like spontaneous mutation. NeuroReport 19:739–743PubMedCrossRef

52.

Serretti A, Chiesa A, Calati R, Linotte S, Sentissi O, Papageorgiou K, Kasper S, Zohar J, De Ronchi D, Mendlewicz J, Amital D, Montgomery S, Souery D (2012) Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci (in press)

53.

Shih JC, Chen K, Ridd MJ (1999) Monoamine oxidase: from genes to behavior. Annu Rev Neurosci 22:197–217PubMedCrossRef

54.

Shih JC, Grimsby J, Chen K, Zhu QS (1993) Structure and promoter organization of the human monoamine oxidase A and B genes. J Psychiatry Neurosci 18:25–32PubMed

55.

Sjoberg RL, Nilsson KW, Wargelius HL, Leppert J, Lindstrom L, Oreland L (2007) Adolescent girls and criminal activity: role of MAOA-LPR genotype and psychosocial factors. Am J Med Genet B Neuropsychiatr Genet 144B:159–164PubMedCrossRef

56.

Skondras M, Markianos M, Botsis A, Bistolaki E, Christodoulou G (2004) Platelet monoamine oxidase activity and psychometric correlates in male violent offenders imprisoned for homicide or other violent acts. Eur Arch Psychiatry Clin Neurosci 254:380–386PubMedCrossRef

57.

Spielberger CD, Reheiser EC, Sydeman SJ (1995) Measuring the experience, expression, and control of anger. Issues Compr Pediatr Nurs 18:207–232PubMedCrossRef

58.

Tadic A, Muller MJ, Rujescu D, Kohnen R, Stassen HH, Dahmen N, Szegedi A (2007) The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression. Am J Med Genet B Neuropsychiatr Genet 144B:325–331PubMedCrossRef

59.

Tadic A, Rujescu D, Muller 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

60.

Tadic A, Rujescu D, Szegedi A, Giegling I, Singer P, Moller HJ, Dahmen N (2003) Association of a MAOA gene variant with generalized anxiety disorder, but not with panic disorder or major depression. Am J Med Genet B Neuropsychiatr Genet 117B:1–6PubMedCrossRef

61.

Wargelius HL, Malmberg K, Larsson JO, Oreland L (2012) Associations of MAOA-VNTR or 5HTT-LPR alleles with attention-deficit hyperactivity disorder symptoms are moderated by platelet monoamine oxidase B activity. Psychiatr Genet 22:42–45PubMedCrossRef

62.

Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J (2007) Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural conduction. Physiol Behav 92:245–249PubMedCrossRef

63.

Wasserman GA, McReynolds LS (2006) Suicide risk at juvenile justice intake. Suicide Life Threat Behav 36:239–249PubMedCrossRef

64.

Weder N, Yang BZ, Douglas-Palumberi H, Massey J, Krystal JH, Gelernter J, Kaufman J (2009) MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma. Biol Psychiatry 65:417–424PubMedCrossRef

65.

Widom CS, Brzustowicz LM (2006) MAOA and the “cycle of violence:” childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biol Psychiatry 60:684–689PubMedCrossRef

66.

Xu Z, Zhang Z, Shi Y, Pu M, Yuan Y, Zhang X, Li L (2011) Influence and interaction of genetic polymorphisms in catecholamine neurotransmitter systems and early life stress on antidepressant drug response. J Affect Disord 133:165–173PubMedCrossRef

67.

Zhang J, Chen Y, Zhang K, Yang H, Sun Y, Fang Y, Shen Y, Xu Q (2010) A cis-phase interaction study of genetic variants within the MAOA gene in major depressive disorder. Biol Psychiatry 68:795–800PubMedCrossRef

Title: MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls
Authors: Niki Antypa
Ina Giegling
Raffaella Calati
Barbara Schneider
Annette M. Hartmann
Marion Friedl
Bettina Konte
Loredana Lia
Diana De Ronchi
Alessandro Serretti
Dan Rujescu
Publication date: 01-08-2013
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Psychiatry and Clinical Neuroscience / Issue 5/2013
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-012-0378-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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