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The effects of child maltreatment on early signs of antisocial behavior: Genetic moderation by tryptophan hydroxylase, serotonin transporter, and monoamine oxidase A genes

  • Dante Cicchetti (a1) (a2), Fred A. Rogosch (a2) and Eric L. Thibodeau (a1)

Abstract

Gene–environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes were examined: tryptophan hydroxylase 1 (TPH1), serotonin transporter linked polymorphic region (5-HTTLPR), and monoamine oxidase A (MAOA) upstream variable number tandem repeat. In addition to child maltreatment status, we considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer, and adult counselor reports. In a series of analyses of covariance, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all report forms. Genetic effects operated primarily in the context of gene–environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5-HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer reports of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. The TPH1 and 5-HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult reports of antisocial behavior; again, the genetic effects were strongest for children who were abused. In addition, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult reports of antisocial behavior. The findings elucidate how genetic variation contributes to identifying which maltreated children are most vulnerable to antisocial development.

Copyright

Corresponding author

Address correspondence and reprint requests to: Dante Cicchetti, Institute of Child Development, University of Minnesota, 51 East River Road, Minneapolis, MN 55455; E-mail: cicchett@umn.edu.

References

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Achenbach, T. M. (1991). Manual for the Child Behavior Checklist/4–18 and 1991 Profile. Burlington, VT: University of Vermont, Department of Psychiatry.
Aslund, C., Nordquist, N., Comasco, E., Leppert, J., Oreland, L., & Nilsson, K. W. (2011). Maltreatment, MAOA, and delinquency: Sex differences in gene–environment interaction in a large population-based cohort of adolescents. Behavior Genetics, 41, 262272.
Azar, S. T. (2002). Parenting and child maltreatment. In Bornstein, M. H. (Ed.), Handbook of parenting: Social conditions and applied parenting (Vol. 4, 2nd ed., pp. 361388). Mahwah, NJ: Erlbaum.
Banny, A., Cicchetti, D., Rogosch, F. A., Crick, N. R., & Oshri, A. (in press). Vulnerability to depression: A moderated mediation model of the roles of child maltreatment, peer victimization, and serotonin transporter linked polymorphic region genetic variation among children from low socioeconomic status backgrounds. Development and Psychopathology.
Barnett, D., Manly, J. T., & Cicchetti, D. (1993). Defining child maltreatment: The interface between policy and research. In Cicchetti, D. & Toth, S. L. (Eds.), Child abuse, child development, and social policy (pp. 774). Norwood, NJ: Ablex.
Beach, S. R., Brody, G. H., Gunter, T. D., Packer, H., Wernett, P., & Philibert, R. A. (2010). Child maltreatment moderates the association of MAOA with symptoms of depression and antisocial personality disorder. Journal of Family Psychology, 24, 1220.
Bolger, K. E., Patterson, C. J., & Kupersmidt, J. B. (1998). Peer relationships and self-esteem among children who have been maltreated. Child Development, 69, 11711197.
Bukowski, W. M., Sippola, L., Hoza, B., & Newcomb, A. F. (2000). Pages from a sociometric notebook: An analysis of nomination and rating scale measures of acceptance, rejection, and social preference. In Cillessen, A. H. N. & Bukowski, W. M. (Eds.), New directions for child and adolescent development: Vol. 88. Recent advances in the measurement of acceptance and rejection in the peer system (pp. 1126). San Francisco, CA: Jossey–Bass.
Carlson, V., Cicchetti, D., Barnett, D., & Braunwald, K. (1989). Disorganized/disoriented attachment relationships in maltreated infants. Developmental Psychology, 25, 525531.
Caspi, A., Hariri, A., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene (5-HTT) and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527.
Caspi, A., McClay, J., Moffitt, T., Mill, J., Martin, J., Craig, I. W., et al. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851854.
Cicchetti, D. (2002). The impact of social experience on neurobiological systems: Illustration from a constructivist view of child maltreatment. Cognitive Development, 17, 14071428.
Cicchetti, D. (2010). Resilience under conditions of extreme stress: A multilevel perspective. World Psychiatry, 9, 110.
Cicchetti, D., & Lynch, M. (1993). Toward an ecological/transactional model of community violence and child maltreatment: Consequences for children's development. Psychiatry, 56, 96118.
Cicchetti, D., & Lynch, M. (1995). Failures in the expectable environment and their impact on individual development: The case of child maltreatment. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology: Risk, disorder, and adaptation (Vol. 2, pp. 3271). New York: Wiley.
Cicchetti, D., & Manly, J. T. (1990). A personal perspective on conducting research with maltreating families: Problems and solutions. In Brody, G. & Sigel, I. (Eds.), Methods of family research: Families at risk (Vol. 2, pp. 87133). Hillsdale, NJ: Erlbaum.
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597600.
Cicchetti, D., & Rogosch, F. A. (2001). The impact of child maltreatment and psychopathology upon neuroendocrine functioning. Development and Psychopathology, 13, 783804.
Cicchetti, D., Rogosch, F. A., Sturge-Apple, M., & Toth, S. L. (2010). Interaction of child maltreatment and 5-HTT polymorphisms: Suicidal ideation among children from low-SES backgrounds. Journal of Pediatric Psychology, 35, 536546.
Cicchetti, D., Rogosch, F. A., & Toth, S. L. (2006). Fostering secure attachment in infants in maltreating families through preventive interventions. Development and Psychopathology, 18, 623650.
Cicchetti, D., & Toth, S. L. (1995). A developmental psychopathology perspective on child abuse and neglect. Journal of the American Academy of Child & Adolescent Psychiatry, 34, 541565.
Cicchetti, D., & Toth, S. L. (2005). Child maltreatment. Annual Review of Clinical Psychology, 1, 409438.
Cicchetti, D., Toth, S. L., & Manly, J. T. (2003). Maternal Maltreatment Interview. Unpublished manuscript, Rochester, NY.
Cicchetti, D., Toth, S.L. , Nilsen, W. J., & Manly, J. T. (in press). What do we know and why does it matter? The dissemination of evidence-based interventions for child maltreatment. In Schaffer, H. R. & Durkin, K. (Eds.), Blackwell handbook of developmental psychology in action. Oxford: Blackwell.
Coccaro, E. F., Kavoussi, R. J., Cooper, T. B., & Hauger, R. L. (1997). Central serotonin activity and aggression: Inverse relationship with prolactin response to d-fenfluramine, but not CSF 5-HIAA concentration, in human subjects. American Journal of Psychiatry, 154, 14301435.
Coie, J. D., & Dodge, K. A. (1983). Continuities and changes in children's social status: A five-year longitudinal study. Merrill–Palmer Quarterly, 29, 261282.
DeBellis, M. D. (2001). Developmental traumatology: The psychobiological development of maltreated children and its implications for research, treatment, and policy. Development and Psychopathology, 13, 539564.
DeBellis, M. D. (2005). The psychobiology of neglect. Child Maltreatment, 10, 150172.
DeYoung, C., Cicchetti, D., Rogosch, F. A., Gray, J., Eastman, M., & Grigorenko, E. (2011). Sources of cognitive exploration: Genetic variation in the prefrontal dopamine system predicts openness/intellect. Journal of Research in Personality, 45, 364371.
Dishion, T. J., & Patterson, G. R. (2006). The development and ecology of antisocial behavior. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology: Vol. 3. Risk, disorder, and adaptation (2nd ed., pp. 503541). Hoboken, NJ: Wiley.
Dodge, K. A., Pettit, G. S., & Bates, J. E. (1997). How the experience of early physical abuse leads children to become chronically aggressive. In Cicchetti, D. & Toth, S. L. (Eds.), Rochester Symposium on Developmental Psychopathology: Trauma: Perspectives on theory, research, and intervention (Vol. 8, pp. 263288). Rochester, NY: University of Rochester Press.
Douglas, K., Chan, G., Gelernter, J., Arias, A. J., Anton, R. F., Poling, J., et al. (2011). 5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder. Psychiatric Genetics, 21, 240248.
Ducci, F., Enoch, M. A., Hodgkinson, C., Xu, K., Catena, M., Robin, R. W., et al. (2008). Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women. Molecular Psychiatry, 13, 334347.
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049.
Eckenrode, J., Laird, M., & Doris, J. (1993). School performance and disciplinary problems among abused and neglected children. Developmental Psychology, 29, 5362.
English, D. J., Upadhyaya, M. P., Litrownik, A. J., Marshall, J. M., Runyan, D. K., Graham, J. C., et al. (2005). Maltreatment's wake: The relationship of maltreatment dimensions to child outcomes. Child Abuse & Neglect, 29, 597619.
Fergusson, D. M., Boden, J. M., Horwood, L. J., Miller, A. L., & Kennedy, M. A. (2011). MAOA, abuse exposure and antisocial behaviour: 30-year longitudinal study. British Journal of Psychiatry, 198, 457463.
Frick, P. J. & Viding, E. M. (2009). Antisocial behavior from a developmental psychopathology perspective. Development and Psychopathology, 21, 11111131.
Gelertner, J., Kranzler, H., & Cubells, J. F. (1997). Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Human Genetics, 101, 243246.
Hart, H., & Rubia, K. (2012). Neuroimaging of child abuse: A critical review. Frontiers in Human Neuroscience, 6, 52.
Hutchison, K. E., Stallings, M., McGeary, J., & Bryan, A. (2004). Population stratification in the candidate gene study: Fatal threat or red herring? Psychological Bulletin, 130, 6679.
Jaffee, S. R., Caspi, A., Moffitt, T. E., & Taylor, A. (2004). Physical maltreatment victim to antisocial child: Evidence of an environmentally mediated process. Journal of Abnormal Psychology, 113, 4455.
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444454.
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., et al. (2006). MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11, 903913.
Kruesi, M. J. P., Rapoport, J. L., Hamburger, S., Hibbs, E., Potter, W. Z., Lenane, M., et al. (1990). Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Archives of General Psychiatry, 47, 419426.
Lansford, J., Dodge, K., Pettit, G., Bates, J., Crozier, J., & Kaplow, J. (2002). A 12-year prospective study of the long-term effects of early child physical maltreatment on psychological, behavioral, and academic problems in adolescence. Archives of Pediatrics and Adolescent Medicine, 156, 824830.
Lesch, K. P., Bengel, D., Heils, A., & Sabol, S. Z. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 15271531.
Li, J. J., & Lee, S. S. (2010). Latent class analysis of antisocial behavior: Interaction of serotonin transporter genotype and maltreatment. Journal of Abnormal Child Psychology, 38, 789801.
Loeber, R., & Farrington, D. P. (2001). Child delinquents: Development, intervention, and service needs. Thousand Oaks, CA: Sage.
Loeber, R., Farrington, D. P., Stouthamer-Loeber, M., & Van Kammen, W. B. (1998). Multiple risk factors for multiproblem boys: Co-occurrence of delinquency, substance use, attention deficit, conduct problems, physical aggression, covert behavior, depressed mood, and shy/withdrawn behavior. In Jessor, R. (Ed.), New perspectives on adolescent risk behavior (pp. 90149). New York: Cambridge University Press.
Luthar, S. S., Cicchetti, D., & Becker, B. (2000). The construct of resilience: A critical evaluation and guidelines for future work. Child Development, 71, 543562.
Manly, J. T. (2005). Advances in research definitions of child maltreatment. Child Abuse & Neglect, 29, 425439.
Manly, J. T., Cicchetti, D., & Barnett, D. (1994). The impact of subtype, frequency, chronicity, and severity of child maltreatment on social competence and behavior problems. Development and Psychopathology, 6, 121143.
Manly, J. T., Kim, J. E., Rogosch, F. A., & Cicchetti, D. (2001). Dimensions of child maltreatment and children's adjustment: Contributions of developmental timing and subtype. Development and Psychopathology, 13, 759782.
Mann, J. J. (1999). Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology, 21, 99S105S.
Manuck, S. B., Flory, J. D., Ferrell, R. E., Dent, K. M., Mann, J. J., & Muldoon, M. F. (1999). Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biological Psychiatry, 45, 603614.
Masten, A. S. (2001). Ordinary magic: Resilience processes in development. American Psychologist, 56, 227238.
McCrory, E., & Viding, E. (2010). The neurobiology of maltreatment and adolescent violence. Lancet, 375, 18561857.
Moffitt, T. E. (1993). Adolescence-limited and life-course-persistent anti-social behavior: A developmental taxonomy. Psychological Review, 100, 674701.
Moffitt, T. E. (2006). Life-course-persistent versus adolescence-limited antisocial behavior. In Cicchetti, D. & Cohen, D. (Eds.), Developmental psychopathology: Vol. 3. Risk, disorder, and adaptation (2nd ed., pp. 570598). Hoboken, NJ: Wiley.
Moffitt, T. E., Caspi, A., & Rutter, M. (2005). Measured gene–environment interactions in psychopathology. Perspectives in Psychological Science, 1, 527.
Pierucci-Lagha, A., Gelernter, J., Chan, G., Arias, A., Cubells, J. F., Farrer, L., et al. (2007). Reliability of DSM-IV diagnostic criteria using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Drug and Alcohol Dependence, 91, 8590.
Pollak, S. D., Cicchetti, D., Hornung, K., & Reed, A. (2000). Recognizing emotion in faces: Developmental effects of child abuse and neglect. Developmental Psychology, 36, 679688.
Richters, J. E., & Cicchetti, D. (1993). Mark Twain meets DSM-III-R: Conduct disorder, development, and the concept of harmful dysfunction. Development and Psychopathology, 5, 529.
Rogosch, F. A., Cicchetti, D., Shields, A., & Toth, S. L. (1995). Parenting dysfunction in child maltreatment. In Bornstein, M. H. (Ed.), Handbook of parenting (Vol. 4, pp. 127159). Hillsdale, NJ: Erlbaum.
Rujescu, D., Giegling, I., Bondy, B., Gietl, A., Zill, P., & Moller, H. J. (2002). Association of anger-related traits with SNPs in the TPH gene. Molecular Psychiatry, 7, 10231029.
Rutter, M. (2012). Resilience as a dynamic concept. Development and Psychopathology, 24, 335344.
Sabol, S. Z., Hu, S., & Hamer, D. (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics, 103, 273279.
Sedlak, A. J., Mettenburg, J., Basena, M., Petta, I., McPherson, K., Greene, A., et al. (2010). Fourth National Incidence Study of Child Abuse and Neglect (NIS–4): Report to Congress, executive summary. Washington, DC: US Department of Health and Human Services, Administration for Children and Families.
Shields, A., & Cicchetti, D. (1997). Emotion regulation among school-age children: The development and validation of a new criterion Q-Sort Scale. Developmental Psychology, 33, 906916.
Shields, A., & Cicchetti, D. (2001). Parental maltreatment and emotion dysregulation as risk factors for bullying and victimization in middle childhood. Journal of Clinical Child Psychology, 30, 349363.
Shonk, S. M., & Cicchetti, D. (2001). Maltreatment, competency deficits, and risk for academic and behavioral maladjustment. Developmental Psychology, 37, 314.
Teisl, M., & Cicchetti, D. (2008). Physical abuse, cognitive and emotional processes, and aggressive/disruptive behavior problems. Social Development, 17, 123.
Trickett, P. K., & McBride-Chang, C. (1995). The developmental impact of different types of child abuse and neglect. Developmental Review, 15, 311337.
Weder, N., Yang, B. Z., Douglas-Palumberi, H., Massey, J., Krystal, J. H., Gelernter, J., et al. (2009). MAOA genotype, maltreatment, and aggressive behavior: The changing impact of genotype at varying levels of trauma. Biological Psychiatry, 65, 417424.
Widom, C. S. (1989). The cycle of violence. Science, 244, 160166.
Widom, C. S., & Brzustowicz, L. M. (2006). MAOA and the “cycle of violence”: Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological Psychiatry, 60, 684689.
Williams, R. B., Marchuk, D. A., Gadde, K. M., Barefoot, J. C., Grichnik, K., Helms, M. J., et al. (2003). Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology, 28, 533541.
Youdim, M. B., Edmondson, D., & Tipton, K. F. (2006). The therapeutic potential of monoamine oxidase inhibitors. National Reviews of Neuroscience, 7, 295309.
Youdim, M. B. H., Finberg, J. P. M., & Tipton, K. F. (1988). Monoamine oxidase. In Trendelemburg, U. & Weiner, U. (Eds.), Catechloamine II (pp. 192199). Berlin: Springer Verlag.

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