Child Abuse and Neglect, MAOA, and Mental Health Outcomes: A Prospective Examination


      Studies have examined the interaction of MAOA genotype with childhood maltreatment in relation to depressive symptomatology and alcohol abuse with conflicting findings. Both high- and low-activity allele combinations have been shown to be protective for maltreated children with direction of findings varying by study methodology and participants' sex.


      Participants in a prospective cohort design study involving court-substantiated cases of child abuse and neglect and a matched comparison group were followed up into adulthood and interviewed (N = 802). Eighty-two percent consented to provide blood, 631 gave permission for DNA extraction and analyses, and 575 were included in the final sample. This sample included male, female, white, and nonwhite (primarily black) participants. Symptoms of dysthymia, major depression, and alcohol abuse were assessed using the National Institutes of Mental Health Diagnostic Interview Schedule-III-R.


      Significant three-way interactions, MAOA genotype by abuse by sex, predicted dysthymic symptoms. Low-activity MAOA genotype buffered against symptoms of dysthymia in physically abused and multiply-maltreated women. Significant three-way interactions, MAOA genotype by sexual abuse by race, predicted all outcomes. Low-activity MAOA genotype buffered against symptoms of dysthymia, major depressive disorder, and alcohol abuse for sexually abused white participants. The high-activity genotype was protective in the nonwhite sexually abused group.


      This prospective study provides evidence that MAOA interacts with child maltreatment to predict mental health outcomes. Reasons for sex differences and race findings are discussed.

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        • Widom C.S.
        • DuMont K.A.
        • Czaja S.J.
        A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up.
        Arch Gen Psychiatry. 2007; 64: 176-187
        • Libby A.M.
        • Orton H.D.
        • Novis D.K.
        • Beals J.
        • Manson S.M.
        Al SUPERPFP Team.
        Psychol Med. 2005; 35: 329-340
        • Gibb B.E.
        • Butler A.C.
        • Beck J.S.
        Childhood abuse, depression, and anxiety in adult psychiatric outpatients.
        Depress Anxiety. 2003; 17: 226-228
        • Brown G.R.
        • Anderson B.
        Psychiatric morbidity in adult inpatients with childhood histories of sexual and physical abuse.
        Am J Psychiatry. 1991; 148: 55-61
        • Kessler R.C.
        • Crum R.M.
        • Warner L.A.
        • Nelson C.B.
        Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey.
        Arch Gen Psychiatry. 1997; 54: 313-321
        • McCauley J.
        • Kern D.E.
        • Kolodner K.
        • Dill L.
        • Schroeder A.D.
        • DeChant H.K.
        • et al.
        Clinical characteristics of women with a history of childhood abuse: Unhealed wounds.
        JAMA. 1997; 277: 1362-1368
        • Weiss E.L.
        • Longhurst J.G.
        • Mazure C.M.
        Childhood sexual abuse as a risk factor for depression in women: Psychosocial and neurobiological correlates.
        Am J Psychiatry. 1999; 156: 816-828
        • Kendler K.S.
        • Bulik C.M.
        • Silberg J.
        • Hettema J.M.
        • Myers J.
        • Prescott C.A.
        Childhood sexual abuse and adult psychiatric and substance use disorders in women: An epidemiological and cotwin control analysis.
        Arch Gen Psychiatry. 2000; 57: 953-959
        • Bifulco A.
        • Brown G.W.
        • Adler Z.
        Early sexual abuse and clinical depression in adult life.
        Br J Psychiatry. 1991; 159: 115-122
        • Sartor C.E.
        • Agrawal A.
        • McCutcheon V.V.
        • Duncan A.E.
        • Lynskey M.T.
        Disentangling the complex association between childhood sexual abuse and alcohol-related problems: A review of methodological issues and approaches.
        J Stud Alcohol Drugs. 2008; 69: 718-727
        • Nelson E.
        • Heath A.
        • Madden P.
        • Cooper M.
        • Dinwiddie S.
        • Bucholz K.
        • et al.
        Association between self-reported childhood sexual abuse and adverse psychosocial outcomes: Results from a twin study.
        Arch Gen Psychiatry. 2002; 59: 139-145
        • Brems C.
        • Johnson M.E.
        • Neal D.
        • Freemon M.
        Childhood abuse history and substance use among men and women receiving detoxification services.
        Am J Drug Alcohol Abuse. 2004; 30: 799-821
        • Fergusson D.M.
        • Lynskey M.T.
        Physical punishment/maltreatment during childhood and adjustment in young adulthood.
        Child Abuse Negl. 1997; 21: 617-630
        • Galaif E.R.
        • Stein J.A.
        • Newcomb M.D.
        • Bernstein D.P.
        Gender differences in the prediction of problem alcohol use in adulthood: Exploring the influence of family factors and childhood maltreatment.
        J Stud Alcohol. 2001; 62: 486-493
        • Wilsnack S.C.
        • Vogeltanz N.D.
        • Klassen A.D.
        • Harris T.R.
        Childhood sexual abuse and women's substance abuse: National survey findings.
        J Stud Alcohol. 1997; 58: 264-271
        • Dube S.R.
        • Anda R.F.
        • Felitti V.J.
        • Edwards V.J.
        • Croft J.B.
        Adverse childhood experiences and personal alcohol abuse as an adult.
        Addict Behav. 2002; 27: 713-725
        • Maxfield M.G.
        • Widom C.S.
        The cycle of violence: Revisited six years later.
        Arch Pediatr Adolesc Med. 1996; 150: 390-395
        • Widom C.S.
        The cycle of violence.
        Science. 1989; 244: 160-166
        • Widom C.S.
        • Marmorstein N.R.
        • White H.R.
        Childhood victimization and illicit drug use in middle adulthood.
        Psychol Addict Behav. 2006; 20: 394-403
        • McGloin J.M.
        • Widom C.S.
        Resilience among abused and neglected children grown up.
        Dev Psychopathol. 2001; 13: 1021-1038
        • DuMont K.A.
        • Widom C.S.
        • Czaja S.J.
        Predictors of resilience in abused and neglected children grown-up: The role of individual and neighborhood characteristics.
        Child Abuse Negl. 2007; 31: 255-274
        • Collishaw S.
        • Pickles A.
        • Messer J.
        • Rutter
        • Shearer C.
        • Maughan B.
        Resilience to adult psychopathology following childhood maltreatment: Evidence from a community sample.
        Child Abuse Negl. 2007; 31: 211-229
        • Martin J.L.
        • Anderson J.C.
        • O'Shea M.L.
        • Mullen D.E.
        Factors that mediate between child sexual abuse and adult psychological outcome.
        Psychol Med. 1995; 25: 127-142
        • Cicchetti D.
        • Rogosch F.A.
        • Lynch M.
        • Holt K.D.
        Resilience in maltreated children: Processes leading to adaptive outcomes.
        Dev Psychopathol. 1993; 5: 629-647
        • Cicchetti D.
        • Rogosch F.A.
        The role of self-organization in the promotion of resilience in maltreated children.
        Dev Psychopathol. 1997; 9: 797-815
        • Heller S.S.
        • Larrieu J.A.
        • D'Imperio R.
        • Boris N.W.
        Research on resilience to child maltreatment: Empirical considerations.
        Child Abuse Negl. 1999; 23: 321-338
        • Jaffee S.
        • Caspi A.
        • Moffitt T.E.
        • Polo-Tomas M.
        • Taylor A.
        Individual, family, and neighborhood factors distinguish resilient from non-resilient maltreated children: A cumulative stressors model.
        Child Abuse Negl. 2007; 31: 231-253
        • Levy E.R.
        • Powell J.F.
        • Buckle V.J.
        • Hsu Y.P.
        • Breakfield X.O.
        • Craig I.W.
        Localization of human monoamine oxidase-A gene to Xp11.23-11.4 in situ hybridization: Implications for Norrie disease.
        Genomics. 1989; 5: 368-370
        • Sabol S.Z.
        • Hu S.
        • Hamer D.
        A functional polymorphism in the monoamine oxidase: A gene promotor.
        Hum Genet. 1998; 103: 273-279
        • Deckert J.
        • Catalano M.
        • Syagailo Y.V.
        • Bosi M.
        • Okladnova O.
        • Di Bella D.
        • et al.
        Excess of high activity monoamine oxidase A gene promotor alleles in female patients with panic disorder.
        Hum Mol Genet. 1999; 8: 621-624
        • Denney R.M.
        • Koch H.
        • Craig I.W.
        Association between monoamine oxidase A activity in human male skin fibroblasts and genotype of the MAOA promotor-associated variable number tandem repeat.
        Hum Genet. 1999; 105: 542-551
        • Shih J.C.
        • Thompson R.F.
        Monoamine oxidase in neuropsychiatry and behavior.
        Am J Hum Genet. 1999; 65: 593-598
        • Keltikangas-Jarvinen L.
        • Salo J.
        Dopamine and serotonin systems modify environmental effects on human behavior: A review.
        Scan J Psychol. 2009; 50: 574-582
        • Horwitz A.V.
        • Widom C.S.
        • McLaughlin J.
        • White H.R.
        The impact of early childhood abuse and neglect on adult mental health: A prospective study.
        J Health Soc Behav. 2001; 42: 184-201
        • Allen B.
        An analysis of the impact of diverse forms of childhood psychological maltreatment on emotional adjustment in early adulthood.
        Child Maltreat. 2008; 13: 307-312
        • Widom C.S.
        • White H.R.
        • Czaja S.J.
        • Marmorstein N.R.
        Long-term effects of child abuse and neglect on alcohol use and excessive drinking in middle adulthood.
        J Stud Alcohol Drugs. 2007; 68: 317-326
        • Caspi A.
        • McClay J.
        • Moffitt T.E.
        • Mill J.
        • Martin J.
        • Craig I.W.
        • et al.
        Role of genotype in cycle of violence in maltreated children.
        Science. 2002; 297: 851-854
        • Foley D.L.
        • Eaves L.J.
        • Wormley B.
        • Silberg J.L.
        • Maes H.M.
        • Kuhn J.
        • et al.
        Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder.
        Arch Gen Psychiatry. 2004; 61: 738-744
        • Nilsson K.W.
        • Sjoberg R.L.
        • Damberg M.
        • Leppert J.
        • Ohrvik J.
        • Alm P.O.
        • et al.
        Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity.
        Biol Psychiatry. 2006; 59: 121-127
        • Kim-Cohen J.
        • Caspi A.
        • Taylor A.
        • Williams B.
        • Newcombe R.
        • Craig I.W.
        • et al.
        MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis.
        Mol Psychiatry. 2006; 11: 903-913
        • Widom C.S.
        • Brzustowicz L.M.
        MAOA and the “cylce of violence”: Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior.
        Biol Psychiatry. 2006; 60: 684-689
        • Weder N.
        • Yang B.Z.
        • Douglas-Palumberi H.
        • Massey J.
        • Krystal J.H.
        • Gelernter J.
        • et al.
        MAOA genotype, maltreatment, aggressive behavior: The changing impact of genotype at varying levels of trauma.
        Biol Psychiatry. 2009; 65: 417-424
        • Prom-Wormley E.S.
        • Eaves L.J.
        • Foley D.L.
        • Archer K.J.
        • Wormley B.K.
        • Maes H.H.
        • et al.
        Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females.
        Psychol Med. 2009; 39: 579-590
        • Huizinga D.
        • Haberstick B.C.
        • Smolen A.
        • Menard S.
        • Young S.E.
        • Corley R.P.
        • et al.
        Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype.
        Biol Psychiatry. 2005; 60: 677-683
        • van der Vegt E.J.M.
        • Oostra B.A.
        • Atrias-Vasquez A.
        • van der Ende J.
        • Verhulst F.C.
        • Tiemeier H.
        High activity of monoamine oxidase A is associated with externalizing behaviour in maltreated and nonmaltreated adoptees.
        Psychiatr Genet. 2009; 19: 209-211
        • Taylor A.
        • Kim-Cohen J.
        Meta-analysis of gene–environment interactions in developmental psychopathology.
        Dev Psychopathol. 2007; 19: 1029-1037
        • Sjoberg R.L.
        • Nilsson K.W.
        • Wargelius H.
        • Leppert J.
        • Lindstrom L.
        • Oreland L.
        Adolescent girls and criminal activity: Role of MAOA-LPR genotype and psychosocial factors.
        Am J Med Genet Part B Neuropsychiatr Genet. 2007; 144B: 159-164
        • Aslund C.
        • Nordquist N.
        • Comasco E.
        • Leppert J.
        • Oreland L.
        • Nilsson K.
        Maltreatment, MAOA, and delinquency: Sex differences in gene–environment interaction in a large population-based cohort of adolescents.
        Behav Genet. 2010; 41: 262-272
        • Cicchetti D.
        • Rogosch F.A.
        • Sturge-Apple M.L.
        Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: Depressive symptomatology among adolescents from low socioeconomic status backgrounds.
        Dev Psychopathol. 2007; 19: 1161-1180
        • Beach S.R.H.
        • Brody G.H.
        • Gunter T.D.
        • Packer H.
        • Wernett P.
        • Philibert R.A.
        Child maltreatment moderates the association of MAOA with symptoms of depression and antisocial personality disorder.
        J Fam Psychol. 2010; 24: 12-20
        • Ducci F.
        • Enoch M.A.
        • Hodgkinson C.
        • Xu K.
        • Catena M.
        • Robin R.W.
        • et al.
        Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women.
        Mol Psychiatry. 2008; 13: 334-347
        • Nilsson K.W.
        • Wargelius H.
        • Sjoberg R.L.
        • Leppert J.
        • Oreland L.
        The MAO-A gene, platelet MAOA-B activity and psychosocial environment in adolescent female alcohol-related problem behaviour.
        Drug Alcohol Depend. 2008; 93: 51-62
        • Nilsson K.
        • Comasco E.
        • Aslund C.
        • Nordquist N.
        • Leppert J.
        • Oreland L.
        MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption.
        Addict Biol. 2010; 6: 347-355
        • Nilsson K.W.
        • Sjoberg R.L.
        • Wargelius H.
        • Leppert J.
        • Lindstrom L.
        • Oreland L.
        The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumption.
        Addiction. 2007; 102: 389-398
        • Widom C.S.
        Child abuse, neglect and adult behavior: Research design and findings on criminality, violence, and child abuse.
        J Orthopsychiatry. 1989; 59: 355-367
        • Edvardsen J.
        • Torgersen S.
        • Roysamb E.
        • Lygren S.
        • Skre I.
        • Onstad S.
        • et al.
        Unipolar depressive disorders have a common genotype.
        J Affect Disord. 2009; 117: 30-41
        • Hollingshead A.B.
        Four-Factor Index of Social Status.
        Yale University, New Haven, CT1975
        • Robins L.N.
        • Helzer J.E.
        • Cottler L.
        • Goldring E.
        National Institute of Mental Health Diagnostic Interview Schedule, Version III—Revised (DIS-III-R).
        Washington University, St. Louis, MO1989
        • Robins L.N.
        • Helzer J.E.
        • Croughan J.L.
        • Ratcliff K.S.
        National Institute of Mental Health diagnostic interview schedule: Its history, characteristics, and validity.
        Arch Gen Psychiatry. 1981; 38: 381-389
        • VonKurff M.
        • Shapiro S.
        • Burke J.D.
        • Teitlebaum M.
        • Skinner E.A.
        • German P.
        • et al.
        Anxiety and depression in a primary care clinic.
        Arch Gen Psychiatry. 1987; 44: 152-156
        • Day I.N.
        • Humphries S.E.
        Electrophoresis for genotyping: microtiter array diagonal gel electrophoresis on horizontal polyacrylamide gels, hydrolink, or agarose.
        Anals of Biochemistry. 1994; 222: 389-395
        • Cohen P.
        • Cohen J.
        • West S.G.
        • Aiken L.S.
        Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences.
        3rd ed. Routledge Academic, Hillsdale, NJ2002
      1. IBM SPSS Software, Version 19. Armonk, NY: IBM Corporation.

        • Baker G.B.
        • Coutts R.T.
        • McKenna K.F.
        • Sherry-McKenna R.L.
        Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: A review.
        J Psychiatry Neurosci. 1992; 17: 206-214
        • Kersting A.
        • Kroker K.
        • Horstmann J.
        • Baune B.T.
        • Hohoff C.
        • Mortensen L.S.
        • et al.
        Association of MAO-A variant with complicated grief in major depression.
        Neuropsychobiology. 2007; 56: 191-196
        • Meyer J.H.
        • Ginovart N.
        • Boovariwala A.
        • Sagrati S.
        • Hussey D.
        • Garcia A.
        • et al.
        Elevated monoamine oxidase A levels in brain.
        Arch Gen Psychiatry. 2006; 63: 1209-1216
        • Ou X.
        • Chen K.
        • Shih J.C.
        Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1.
        J Biol Chem. 2006; 281: 21512-21525
        • Sjoberg R.L.
        • Ducci F.
        • Barr C.S.
        • Newman T.K.
        • Dell'Osso L.
        • Virkkunen M.
        • et al.
        A Non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior.
        Neuropsychopharmacology. 2008; 33: 425-430
        • Collaer M.L.
        • Hines M.
        Human behavioral sex differences: A role of gonadal hormones during early development?.
        Psychol Bull. 1995; 118: 55-107
        • Carrel R.J.
        • Willard H.F.
        X-inactivation profile reveals extensive variability in X-linked gene expression in females.
        Nature. 2005; 434: 400-404
        • Sjöberg R.L.
        • Nilsson K.W.
        • Wargelius H.-L.
        • Leppert J.
        • Lindström L.
        • Oreland L.
        Adolescent girls and criminal activity: Role of MAOA-LPR genotype and psychosocial factors.
        Am J Med Genet Part B Neuropsychiatr Genet. 2007; 114B: 159-164
        • Reynolds S.
        Gene influences the impact of maternal smoking on children's behavioral problems.
        NIDA Publications. 2011; 23: 1-5
        • Cloninger C.R.
        • Bohman M.
        • Sigvardsson S.
        Inheritance of alcohol abuse: Cross-fostering analysis of adopted men.
        Arch Gen Psychiatry. 1981; 38: 861-868

      Linked Article

      • Child Abuse and Psychiatric Illness
        Biological PsychiatryVol. 71Issue 4
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          Child abuse is a nonspecific risk factor associated with an increased risk for a range of psychiatric and substance use disorders. The paper in this issue by Dannlowski et al. (1) adds to a growing body of literature on the mechanisms by which adverse early experiences confer vulnerability to psychiatric illness. The paper by Nikulina et al. (2) delineate further genetic and other factors that account for individual differences in the outcomes of adults who were abused as children.
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