Behavior Genetics

, Volume 40, Issue 5, pp 639–648 | Cite as

Harsh Discipline, Childhood Sexual Assault, and MAOA Genotype: An Investigation of Main and Interactive Effects on Diverse Clinical Externalizing Outcomes

  • Jaime DerringerEmail author
  • Robert F. Krueger
  • Daniel E. Irons
  • William G. Iacono
Original Research


We studied the impact of MAOA genotype, childhood sexual assault, and harsh discipline on clinical externalizing symptoms (substance problems, adult antisocial behavior, and conduct disorder). Participants were 841 individual twins from the Minnesota Twin Family Study assessed through age 25. MAOA genotype was not associated with differences in any phenotype, nor was there a significant interaction between MAOA and harsh discipline for any phenotype or a significant interaction between MAOA and childhood sexual assault for substance problems. We found evidence that childhood sexual assault interacted with MAOA genotype to predict antisocial behavior and conduct disorder symptoms. Individuals with the low MAOA activity genotype who reported childhood sexual assault had more symptoms than individuals with either the high MAOA activity genotype and/or no history of childhood sexual assault. These findings suggest that the previously reported interaction between MAOA and childhood maltreatment may be specific to the antisocial subset of externalizing disorders.


Gene–environment interaction Substance use disorders Antisocial behavior Conduct disorder MAOA Childhood sexual assault Harsh discipline 



NIH grants DA05147 and AA09367.


  1. 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 28:5099–5104. doi: 10.1523/jneuroSCI.0925-08.2008 CrossRefPubMedGoogle Scholar
  2. Beitchman JH, Mik HM, Ehtesham S, Douglas L, Kennedy JL (2004) MAOA and persistent, pervasive childhood aggression. Mol Psychiatry 9:546–547. doi: 10.1038/ CrossRefPubMedGoogle Scholar
  3. Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes? Mol Psychiatry 14:746–754. doi: 10.1038/mp.2009.44 CrossRefPubMedGoogle Scholar
  4. Buckholtz JW, Meyer-Lindenberg A (2008) MAOA and the neurogenetic architecture of human aggression. Trends Neurosci 31:120–129. doi: 10.1016/j.tins.2007.12.006 CrossRefPubMedGoogle Scholar
  5. Burt SA, Krueger RF, McGue M, Iacono WG (2001) Sources of covariation among attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder: the importance of shared environment. J Abnorm Psychol 110:516–525. doi: 10.1037//0021-843X.110.4.516 CrossRefPubMedGoogle Scholar
  6. Carrel L, Willard HF (2005) X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434:400–404. doi: 10.1038/nature03479 CrossRefPubMedGoogle Scholar
  7. 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 297:851–854. doi: 10.1126/science.1072290 CrossRefPubMedGoogle Scholar
  8. 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 8:621–624CrossRefPubMedGoogle Scholar
  9. Ducci F, Enoch MA, Hodgkinson C, Xu K, Cantena M, Robin RW, Goldman D (2008) Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women. Mol Psychiatry 13:334–347. doi: 10.1038/ CrossRefPubMedGoogle Scholar
  10. 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 61:738–744CrossRefPubMedGoogle Scholar
  11. 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 5:e486. doi: 10.1371/journal.pone.0000486 CrossRefGoogle Scholar
  12. Gauderman WJ, Morrison JM (2007) QUANTO version 1.2.3: a computer program for power and sample size calculations for genetic-epidemiology studies.
  13. Gillespie NA, Neale MC, Prescott CA, Aggen SH, Kendler KS (2007) Factor and item-response analysis DSM-IV criteria for abuse of and dependence on cannabis, cocaine, hallucinogens, sedatives, stimulants and opioids. Addiction 102:920–930. doi: 10.1111/j.1360-0443.2007.01804.x CrossRefPubMedGoogle Scholar
  14. 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 16:626–634. doi: 10.1038/sj.ejhg.5201999 CrossRefPubMedGoogle Scholar
  15. Haberstick BC, Lessem JM, Hopfer CJ, Smolen A, Ehringer MA, Timberlake D, Hewitt JK (2005) Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment. Am J Med Genet B 135B:59–64. doi: 10.1002/ajmg.b.30176 CrossRefGoogle Scholar
  16. Harford TC, Yi H, Faden VB, Chen CM (2009) The dimensionality of DSM-IV alcohol use disorders among adolescent and adult drinkers and symptom patterns by age, gender, and race/ethnicity. Alcohol Clin Exp Res 33:1–11. doi: 10.1111/j.1530-0277.2009.00910.x CrossRefGoogle Scholar
  17. Huang Y, Cate SP, Battistuzzi C, Oquendo MA, Brent D, Mann JJ (2004) An association between a functional polymorphism in the monoamine oxidase A gene promoter, impulsive traits, and early abuse experiences. Neuropsychopharmacology 29:1498–1505. doi: 10.1038/sj.npp.1300455 CrossRefPubMedGoogle Scholar
  18. Huizinga D, Haberstick BC, Smolen A, Menard S, Young SE, Corley RP, Stallings MC, Grotpeter J, Hewitt JK (2006) Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype. Biol Psychiatry 60:677–683. doi: 10.1016/j.biopsych.2005.12.022 CrossRefPubMedGoogle Scholar
  19. Iacono WG, McGue M (2002) Minnesota twin family study. Twin Res 5:482–487. doi: 10.1375/twin.5.5.482 CrossRefPubMedGoogle Scholar
  20. Kendler KS, Prescott CA, Myers J, Neale MC (2003) The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch Gen Psychiatry 60:929–937CrossRefPubMedGoogle Scholar
  21. 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 11:903–913. doi: 10.1038/ CrossRefPubMedGoogle Scholar
  22. Kline RB (2005) Principles and practice of structural equation modeling, 2nd edn. Guilford Press, New YorkGoogle Scholar
  23. Koller G, Bondy B, Preuss UW, Bottlender M, Soyka M (2003) No association between a polymorphism in the promoter region of the MAOA gene with antisocial personality traits in alcoholics. Alcohol Alcohol 38:31–34. doi: 10.1093/alcalc/agg003 PubMedGoogle Scholar
  24. Krueger RF, South SC (2009) Externalizing disorders: cluster 5 of the proposed meta-structure for DSM-V and ICD-11. Psychol Med 39:2061–2070. doi: 10.1017/S003329170999032 CrossRefPubMedGoogle Scholar
  25. Krueger RF, Hicks BM, Patrick CJ, Carlson SR, Iacono WG, McGue M (2002) Etiologic connections among substance dependence, antisocial behavior, and personality: modeling the externalizing spectrum. J Abnorm Psychol 111:411–424. doi: 10.1037//0021-843X.111.3.411 CrossRefPubMedGoogle Scholar
  26. Krueger RF, Markon KE, Patrick CJ, Benning SD, Kramer M (2007) Linking antisocial behavior, substance use, and personality: an integrative quantitative model of the adult externalizing spectrum. J Abnorm Psychol 116:645–666. doi: 10.1037/0021-843X.116.4.645 CrossRefPubMedGoogle Scholar
  27. Langenbucher JW, Labouvie E, Martin CS, Sanjuan PM, Bavly L, Kirisci L, Chung T (2004) An application of item response theory analysis to alcohol, cannabis, and cocaine criteria in DSM-IV. J Abnorm Psychol 113:72–80. doi: 10.1037/0021-843X.113.1.72 CrossRefPubMedGoogle Scholar
  28. 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 95:9–23. doi: 10.1016/S0165-1781(00)00162-1 CrossRefPubMedGoogle Scholar
  29. Martin CS, Chung T, Kirisci L, Langenbucher JW (2006) Item response theory analysis of diagnostic criteria for alcohol and cannabis use disorders in adolescents: Implications for DSM-V. J Abnorm Psychol 115:807–814. doi: 10.1037/0021-843X.115.4.807 CrossRefPubMedGoogle Scholar
  30. McDermott R, Tingley D, Cowden J, Frazzetto G, Johnson DDP (2009) Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. Proc Natl Acad Sci USA 106:2118–2123. doi: 10.1073/pnas.0808376106 CrossRefPubMedGoogle Scholar
  31. Munafò MR, Durrant C, Lewis G, Flint J (2009) Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 65:211–219. doi: 10.1016/j.biopsych.2008.06.009 CrossRefPubMedGoogle Scholar
  32. Muthén LK, Muthén BO (1998–2007) Mplus user’s guide, 5th edn. Muthén & Muthén, Los AngelesGoogle Scholar
  33. Nilsson KW, Sjöberg RL, Damberg M, Leppert J, Öhrvik J, Alm PO, Lindström L, Oreland L (2006) Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity. Biol Psychiatry 59:121–127. doi: 10.1016/j.biopsych.2005.06.024 CrossRefPubMedGoogle Scholar
  34. Nilsson KW, Sjöberg RL, Wargelius HL, Leppert J, Lindström L, Oreland L (2007) The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumption. Addiction 102:389–398. doi: 10.1111/j.1360-0443.2006.01702.x CrossRefPubMedGoogle Scholar
  35. Nilsson KW, Wargelius HL, Sjöberg RL, Leppert J, Oreland L (2008) The MAO-A gene, platelet MAO-B activity and psychosocial environment in adolescent female alcohol-related problem behaviour. Drug Alcohol Depend 93:51–62. doi: 10.1016/j.drugalcdep.2007.08.022 CrossRefPubMedGoogle Scholar
  36. Pinsonneault JK, Papp AC, Sadée W (2006) Allelic mRNA expression of X-linked monoamine oxidase a (MAOA) in human brain: dissection of epigenetic and genetic factors. Hum Mol Genet 15:2636–2649. doi: 10.1093/hmg/ddl192 CrossRefPubMedGoogle Scholar
  37. Prom-Wormley EC, Eaves LJ, Foley DL, Gardner CO, Archer KJ, Wormley BK, Maes HH, Riley BP, Silberg JL (2009) Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females. Psychol Med 39:579–590. doi: 10.1017/S0033291708004170 CrossRefPubMedGoogle Scholar
  38. Reich W, Welner Z (1988) Diagnostic interview for children and adolescents—revised: DSM-III-R version (DICA-R). Washington University, St. LouisGoogle Scholar
  39. Reif A, Rosler M, Freitag CM, Schneider M, Eujen A, Kissling C, Wenzler D, Jacob CP, Retz-Junginger P, Thome J, Lesch K, Retz W (2007) Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 32:2375–2383. doi: 10.1038/sj.npp.1301359 CrossRefPubMedGoogle Scholar
  40. Resnick HS, Best CL, Kilpatrick DG, Freedy JR, Falsetti SA (1993) Trauma assessment for adults—self-report version. Unpublished scale. National Crime Victims Research and Treatment Center, Medical University of South Carolina, CharlestonGoogle Scholar
  41. Robins LM, Babor T, Cottler LB (1987) Composite international diagnostic interview: expanded substance abuse module. Authors, St. LouisGoogle Scholar
  42. Sabol SZ, Hu S, Hamer S (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279. doi: 10.1007/s004390050816 CrossRefPubMedGoogle Scholar
  43. Shulz-Heik RJ, Rhee SH, Silvern L, Lessem JM, Haberstick BC, Hopfer C, Hewitt JK (2009) Investigation of genetically mediated child effects on maltreatment. Behav Genet 39:265–276. doi: 10.1007/s10519-009-9261-4 CrossRefGoogle Scholar
  44. Sjöberg RL, Nilsson KW, Wargelius HL, Leppert J, Lindström L, Oreland L (2007) Adolescent girls and criminal activity: role of MAOA-LPR genotype and psychosocial factors. Am J Med Genet B 144B:159–164. doi: 10.1002/ajmg.b.30360 CrossRefGoogle Scholar
  45. Tabery J (2009) From a genetic predisposition to an interactive predisposition: rethinking the ethical implications of screening for gene-environment interactions. J Med Philos 34:27–48. doi: 10.1093/jmp/jhn039 CrossRefPubMedGoogle Scholar
  46. van der Vegt EJM, Oostra BA, Arias-Vasquez A, van der Ende J, Verhulst FC, Tiemeier H (2009) High activity Monoamine oxidase A is associated with externalizing behaviour in maltreated and nonmaltreated adoptees. Psychiatr Genet 19:209–211. doi: 10.1097/YPG.0b013e32832a5084 CrossRefPubMedGoogle Scholar
  47. 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 65:417–424. doi: 10.1016/j.biopsych.2008.09.013 CrossRefPubMedGoogle Scholar
  48. Widom CS, Bzustowicz LM (2006) MAOA and the “cycle of violence”: childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biol Psychiatry 60:684–689. doi: 10.1016/j.biopsych.2006.03.039 CrossRefPubMedGoogle Scholar
  49. Young SE, Stallings MC, Corley RP, Krauter KS, Hewitt JK (2000) Genetic and environmental influences on behavioral disinhibition. Am J Med Genet B 96:684–695. doi: 10.1002/1096-8628(20001009)96:5<684:AID-AJMG16>3.0.CO;2-G CrossRefGoogle Scholar
  50. Young SE, Smolen A, Hewitt JK, Haberstick BC, Stallings MC, Corley RP, Crowley TJ (2006) Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: Failure to confirm in adolescent patients. Am J Psychiatry 163:1019–1025. doi: 10.1176/appi.ajp.163.6.1019 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jaime Derringer
    • 1
    Email author
  • Robert F. Krueger
    • 1
  • Daniel E. Irons
    • 2
  • William G. Iacono
    • 2
  1. 1.Department of PsychologyWashington UniversitySt. LouisUSA
  2. 2.Department of PsychologyUniversity of MinnesotaMinneapolisUSA

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