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Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children

Published online by Cambridge University Press:  25 November 2014

Dante Cicchetti  and
Fred A. Rogosch
Dante Cicchetti*
Affiliation:
University of Minnesota Institute of Child Development University of Rochester Mt. Hope Family Center
Fred A. Rogosch
Affiliation:
University of Rochester Mt. Hope Family Center
*
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.
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Abstract

Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1 haplotype. The findings illustrate the variable influence of specific genotypes in G × E interactions based on variation in maltreatment experiences and the importance of a multigenic approach for understanding influences on depression and internalizing symptoms among African American children.

Type
Regular Articles
Information
Development and Psychopathology , Volume 26 , Special Issue 4pt2: Multilevel Developmental Perspectives Toward Understanding Internalizing Psychopathology: Current Research and Future Directions , November 2014 , pp. 1219 - 1239
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Copyright © Cambridge University Press 2014 

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References

Achenbach, T. M. (1991). Manual for the Teacher's Report Form and 1991 Profile. Burlington, VT: University of Vermont, Department of Psychiatry.Google Scholar
Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., et al. (2009). Early adversity and 5-HTT/BDNF genes: New evidence of gene–environment interactions on depressive symptoms in a general population. Psychological Medicine, 39, 1425–1432.CrossRefGoogle ScholarPubMed
Banny, A., Cicchetti, D., Rogosch, F. A., Crick, N. R., & Oshri, A. (2013). Vulnerability to depression: A moderated mediation model of the roles of child maltreatment, peer victimization, and genetic variation among children from low socioeconomic status backgrounds. Development and Psychopathology, 25, 599–614.Google Scholar
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. 7–73). Norwood, NJ: Ablex.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885–908.Google Scholar
Bolger, K. E., & Patterson, C. J. (2001). Pathways from child maltreatment to internalizing problems: Perceptions of control as mediators and moderators. Development and Psychopathology, 13, 913–940.Google Scholar
Bolger, K. E., Patterson, C. J., & Kupersmidt, J. B. (1998). Peer relationships and self-esteem among children who have been maltreated. Child Development, 69, 1171–1197.Google Scholar
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., & Heim, C. (2011). Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene. Development and Psychopathology, 23, 439–452.Google Scholar
Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., et al. (2008). Influence of child abuse on adult depression: Moderation by the corticotrophin-releasing hormone receptor gene. Archives of General Psychiatry, 65, 190–200.Google Scholar
Brodsky, B., & Stanley, B. (2008). Adverse childhood experiences and suicidal behavior. Psychiatric Clinics of North America, 31, 223–235.CrossRefGoogle ScholarPubMed
Brody, G. H., Yu, T., Beach, S. R. H., Windle, M., & Kogan, S. M. (2014). Harsh parenting and adolescent health: A longitudinal analysis with genetic moderation. Health Psychology, 33, 401–409.Google Scholar
Brody, G. H., Yu, T., Chen, Y., Evans, G. W., Beach, S. R. H., Windle, M., et al. (2013). Cumulative socioeconomic status risk, allostatic load, and adjustment: A prospective latent profile analysis with contextual and genetic protective factors. Developmental Psychology, 49, 913–927.CrossRefGoogle ScholarPubMed
Byck, G. R., Bolland, J., Dick, D., Ashbeck, A. W., & Mustanski, B. S. (2013). Prevalence of mental health disorders among low-income African American adolescents. Social Psychiatry and Psychiatric Epidemiology, 48, 1555–1567.Google Scholar
Carson, N., Cook, B., & Alegria, M. (2010). Social determinants of mental health treatment among Haitian, African American, and White youth in community mental health centers. Journal of Health Care for the Poor and Underserved, 21(2 Suppl), 32–48.CrossRefGoogle Scholar
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, 509–527.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H. L., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–389.CrossRefGoogle ScholarPubMed
Cicchetti, D. (2006). Development and psychopathology. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology (Vol. 1, 2nd ed., pp. 1–23). Hoboken, NJ: Wiley.Google Scholar
Cicchetti, D., & Dawson, G. (2002). Multiple levels of analysis. Development and Psychopathology, 14, 417–420.Google Scholar
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: Vol. 2. Risk, disorder, and adaptation (pp. 32–71). New York: Wiley.Google Scholar
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. 87–133). Hillsdale, NJ: Erlbaum.Google Scholar
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597–600.Google Scholar
Cicchetti, D., Rogosch, F. A., Gunnar, M. R., & Toth, S. L. (2010). The differential impacts of early abuse on internalizing problems and diurnal cortisol activity in school-aged children. Child Development, 25, 252–269.Google Scholar
Cicchetti, D., Rogosch, F. A., & Sturge-Apple, M. L. (2007). Interactions of child maltreatment and 5-HTT and monoamine oxidase A polymorphisms: Depressive symptomatology among adolescents from low-socioeconomic status backgrounds. Development and Psychopathology, 19, 1161–1180.Google Scholar
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, 536–546.Google Scholar
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, 541–565.Google Scholar
Cicchetti, D., & Toth, S. L. (2009). The past achievements and future promises of developmental psychopathology: The coming of age of a discipline. Journal of Child Psychology and Psychiatry, 50, 16–25.Google Scholar
Cicchetti, D., & Toth, S. L. (in press). A multilevel perspective on child maltreatment. In Lamb, M. & Coll, C. Garcia (Eds.), Handbook of child psychology and developmental science: Vol. 3. Socioemotional process (7th ed.). Hoboken, NJ: Wiley.Google Scholar
Cicchetti, D., & Tucker, D. (Eds.). (1994). Neural plasticity, sensitive periods, and psychopathology [Special Issue]. Development and Psychopathology, 6, 531–814.Google Scholar
Cicchetti, D., & Valentino, K. (2006). An ecological transactional perspective on child maltreatment: Failure of the average expectable environment and its influence upon child development. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology (Vol. 3, 2nd ed., pp. 129–201). Hoboken, NJ: Wiley.Google ScholarPubMed
Cutuli, J. J., Raby, K. L., Cicchetti, D., Englund, M. M., & Egeland, B. (2013). Contributions of maltreatment and serotonin transporter genotype to depression in childhood, adolescence, and early adulthood. Journal of Affective Disorders, 149, 30–37.Google Scholar
DeYoung, C., Cicchetti, D., & Rogosch, F. A. (2011). Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene. Journal of Child Psychology and Psychiatry, 52, 898–906.Google Scholar
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, 1041–1049.Google Scholar
Duncan, L. E., Pollastri, A. R., & Smoller, J. W. (2014). Mind the gap: Why many geneticists and psychological scientists have discrepant views about gene–environment interaction (G × E) research. American Psychologist, 69, 249.CrossRefGoogle Scholar
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 7–28.Google Scholar
English, D., Lambert, S. F., & Ialongo, N. (2014). Longitudinal associations between experienced racial discrimination and depressive symptoms in African American adolescents. Developmental Psychology, 50, 1190–1196.Google Scholar
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 and Neglect, 29, 594–619.Google Scholar
Escoffier, L., & Lischer, H. (2011). Arlequin version 3.5 [Computer software]. Bern, Switzerland: Swiss Institute of Bioinformatics.Google Scholar
Falush, D., Stephens, M., & Pritchard, J. K. (2003). Inference of population structure using multilocus genotype data: Linked loci and correlated allele frequencies. Genetics, 164, 1567–1587.Google Scholar
Falush, D., Stephens, M., & Pritchard, J. K. (2007). Inference of population structure using multilocus genotype data: Dominant and null alleles. Molecular Ecology Notes, 7, 574–578.Google Scholar
Gelernter, 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, 243–246.Google Scholar
Gottesman, I. I., & Shields, J. (1972). Schizophrenia and genetics: A twin study vantage point. Oxford: Academic Press.Google Scholar
Grigorenko, E. L., & Cicchetti, D. (2012). Genomic sciences for developmentalists: The current state of affairs. Development and Psychopathology, 24, 1157–1164.Google Scholar
Gunnar, M. R., Wenner, J. A., Thomas, K. M., Glatt, C. E., McKenna, M. C., & Clark, A. G. (2012). The brain-derived neurotrophic factor Val66Met polymorphism moderates early deprivation effects on attention problems. Development and Psychopathology, 24, 1215–1223.CrossRefGoogle ScholarPubMed
Heim, C., Newport, J. D., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33, 693–710.Google Scholar
Hu, X., Oroszi, G., Chun, J., Smith, T. L., Goldman, D., & Schuckit, M. A. (2005). An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcoholism: Clinical and Experimental Research, 29, 8–16.Google Scholar
Hubisz, M. J., Falush, D., Stephens, M., & Pritchard, J. K. (2009). Inferring weak population structure with assistance of sample group information Molecular Ecology Resources, 5, 1322–1332.Google Scholar
Kaufman, J., Yang, B., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., et al. (2006). Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673–680.CrossRefGoogle ScholarPubMed
Kaufman, J., Yang, B., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., & Krystal, J. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences, 101, 17316–17321.Google Scholar
Keller, M. C. (2014). Gene × Environment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75, 18–24.Google Scholar
Kodjo, C. M., & Audinger, P. (2004). Predictors for emotionally distressed adolescents to receive mental health care. Journal of Adolescent Health, 35, 369–373.CrossRefGoogle ScholarPubMed
Kovacs, M. (1982). The Children's Depression Inventory: A self-rated depression scale for school-aged youngsters. Unpublished manuscript, University of Pittsburgh.Google Scholar
Kovacs, M. (1992). Children's Depression Inventory manual. North Tonawanda, NY: Multi-Health Systems.Google Scholar
Lai, C. Q., Tucker, K. L., Choudhry, S., Parnell, L. D., Mattei, J., Garcia-Bailo, B., et al. (2009). Population admixture associated with disease prevalence in the Boston Puerto Rican health study. Human Genetics, 125, 199–205.Google Scholar
Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527–1531.Google Scholar
Manly, J. T. (2005). Advances in research definitions of child maltreatment. Child Abuse and Neglect, 29, 425–439.Google Scholar
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, 121–143.Google Scholar
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, 759–782.Google Scholar
Masten, A. S., & Cicchetti, D. (2010). Developmental cascades. Development and Psychopathology, 22, 491–495.Google Scholar
McGrath, L. M., Weill, S., Robinson, E. B., Macrae, R., & Smoller, J. W. (2012). Bringing a developmental perspective to anxiety genetics. Development and Psychopathology, 24, 1179–1193.Google Scholar
Meaney, M. J. (2010). Epigenetics and the biological definition of Gene × Environment interactions. Child Development, 81, 41–79.Google Scholar
Moffitt, T. E., Caspi, A., & Rutter, M. (2005). Measured gene–environment interactions in psychopathology. Perspectives in Psychological Science, 1, 5–27.Google Scholar
Odgerel, Z., Talati, A., Hamilton, S. P., Levinson, D. F., & Weissman, M. M., (2013). Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health's Collaborative Center for Genomic Studies. Translational Psychiatry, 3(9), e307, 1–6.Google Scholar
Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., et al. (2009). Protective effects of CRHR1 gene variants on the development of adult depression following childhood maltreatment. Archives of General Psychiatry, 66, 978–985.CrossRefGoogle ScholarPubMed
Ressler, K. J., Bradley, B., Mercer, K. B., Deveau, T. C., Smith, A. K., Gillespie, C. F., et al. (2010). Polymorphisms in CRHR1 and the serotonin transporter loci: Gene × Gene × Environment interactions on depressive symptoms. American Journal of Medical Genetics, 153B, 812–824.Google Scholar
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.Google Scholar
Szyf, M., & Bick, J. (2013). DNA methylation: A mechanism for embedding early life experiences in the genome. Child Development, 84, 49–57.Google Scholar
Toth, S. L., Manly, J. T., & Cicchetti, D. (1992). Child maltreatment and vulnerability to depression. Development and Psychopathology, 4, 97–112.Google Scholar
Uher, R., Mors, O., Rietschel, M., Rajewska-Rager, A., Petrovic, A., Zobel, A., et al. (2011). Early and delayed onset of response to antidepressants in individual trajectories of change during treatment of major depression: A secondary analysis of data from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. Journal of Clinical Psychiatry, 72, 1478–1484.Google Scholar
Widom, C. S., DuMont, K., & Czaja, S. J. (2007). A prospective investigation of major depressive disorder and co-morbidity in abused and neglected grown-up children (grown up). Archives of General Psychiatry, 64, 49–56.Google Scholar
Yaeger, R., Alvial-Bront, A., Abdul, K., Nolan, P. C., Grann, V. R., Birchette, M. G., et al. (2008). Comparing genetic ancestry and self-described race in African Americans born in the United States and in Africa. Cancer Epidemiology, Biomarkers & Prevention, 17, 1329–1338.CrossRefGoogle ScholarPubMed