Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-22T18:10:50.899Z Has data issue: false hasContentIssue false
  • English
  • Français

An investigation of child maltreatment and epigenetic mechanisms of mental and physical health risk

Published online by Cambridge University Press:  03 October 2016

Dante Cicchetti ,
Susan Hetzel ,
Fred A. Rogosch ,
Elizabeth D. Handley  and
Sheree L. Toth
Dante Cicchetti*
Affiliation:
University of Minnesota Institute of Child Development University of Rochester Mt. Hope Family Center
Susan Hetzel
Affiliation:
University of Minnesota Institute of Child Development
Fred A. Rogosch
Affiliation:
University of Rochester Mt. Hope Family Center
Elizabeth D. Handley
Affiliation:
University of Rochester Mt. Hope Family Center
Sheree L. Toth
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: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

In the present investigation, differential methylation analyses of the whole genome were conducted among a sample of 548 school-aged low-income children (47.8% female, 67.7% Black, M age = 9.40 years), 54.4% of whom had a history of child maltreatment. In the context of a summer research camp, DNA samples via saliva were obtained. Using GenomeStudio, Methylation Module, and the Illumina Custom Model, differential methylation analyses revealed a pattern of greater methylation at low methylation sites (n = 197 sites) and medium methylation sites (n = 730 sites) and less methylation at high methylation sites (n = 907 sites) among maltreated children. The mean difference in methylation between the maltreated and nonmaltreated children was 6.2%. The relative risk of maltreatment with known disease biomarkers was also investigated using GenoGo MetaCore Software. A large number of network objects previously associated with mental health, cancer, cardiovascular systems, and immune functioning were identified evidencing differential methylation among maltreated and nonmaltreated children. Site-specific analyses were also conducted for aldehyde dehydrogenase 2 (ALDH2), ankyrin repeat and kinase domain containing 1 (ANKK1), and nuclear receptor subfamily 3, group C, member 1 (NR3C1) genes, and the results highlight the importance of considering gender and the developmental timing of maltreatment. For ALDH2, the results indicated that maltreated girls evidenced significantly lower methylation compared to nonmaltreated girls, and maltreated boys evidenced significantly higher methylation compared to nonmaltreated boys. Moreover, early onset–not recently maltreated boys evidenced significantly higher methylation at ALDH2 compared to nonmaltreated boys. Similarly, children with early onset–nonrecent maltreatment evidenced significantly higher methylation compared to nonmaltreated children at ANKK1. The site-specific results were not altered by controlling for genotypic variation of respective genes. The findings demonstrate increased risk for adverse physical and mental health outcomes associated with differences in methylation in maltreated children and indicate differences among maltreated children related to developmental timing of maltreatment and gender in genes involved in mental health functioning.

Type
Special Section Articles
Information
Development and Psychopathology , Volume 28 , Special Issue 4pt2: Epigenetics: Development, Psychopathology, Resilience, and Preventive Intervention , November 2016 , pp. 1305 - 1317
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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
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
Cicchetti, D. (1989). How research on child maltreatment has informed the study of child development: Perspectives from developmental psychopathology. In Cicchetti, D. & Carlson, V. (Eds.), Child maltreatment: Theory and research on the causes and consequences of child abuse and neglect (pp. 377–431). New York: Cambridge University Press.Google Scholar
Cicchetti, D., & Barnett, D. (1991). Toward the development of a scientific nosology of child maltreatment. In Grove, W. & Cicchetti, D. (Eds.), Thinking clearly about psychology: Essays in honor of Paul E. Meehl: Personality and psychopathology (Vol. 2). Minneapolis, MN: University of Minnesota Press.Google Scholar
Cicchetti, D., & Lynch, M. (1993). Toward an ecological/transactional model of community violence and child maltreatment: Consequences for children's development. Psychiatry, 56, 96–118.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., & Toth, S. L. (2015a). Handbook of child psychology and developmental science: Vol. 3. Child maltreatment. Hoboken, NJ: Wiley.Google Scholar
Cicchetti, D., & Toth, S. L. (2015b). Multilevel developmental perspectives on child maltreatment. Development and Psychopathology, 27, 1385–1386. doi:10.1017/S0954579415000814 CrossRefGoogle ScholarPubMed
Cicchetti, D., & Toth, S. L. (2016). Child maltreatment and developmental psychopathology: A multilevel perspective. In Cicchetti, D. (Ed.), Developmental psychopathology: Vol. 3. Maladaptation and psychopathology (3rd ed., pp. 457–512). Hoboken, NJ: Wiley.Google Scholar
Cicchetti, D., Toth, S. L., & Manly, J. T. (2003). Maternal Child Maltreatment Interview. Unpublished manuscript, Mt. Hope Family Center.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. Maladaptation and psychopathology (2nd ed., pp. 129–201). Hoboken, NJ: Wiley.Google Scholar
Dick, D. M., & Foroud, T. (2003). Candidate genes for alcohol dependence: A review of genetic evidence from human studies. Alcoholism: Clinical and Experimental Research, 27, 868–879.Google Scholar
Du, P., Zhang, X., Huang, C., Jafari, N., Kibbe, W. A., Hou, L., et al. (2009). Comparison of beta-value and M-Value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics, 11, 587.Google Scholar
Dubowitz, H., Pitts, S. C., Litrownik, A. J., Cox, C. E., Runyan, D., & Black, M. M. (2005). Defining child neglect based on child protective services data. Child Abuse and Neglect, 29, 493–511.CrossRefGoogle ScholarPubMed
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, 597–619.Google Scholar
Esposito, E. A., Jones, M. J., Doom, J. R., MacIssac, J. L., Gunnar, M. R., & Kobor, M.S. (2016). Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity. Development and Psychopathology. Advance online publication. doi:10.1017/S0954579416000055.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
Falush, D., Stephens, M., & Pritchard, J. K. (2007). Inference of population structure using multilocus genotype data: Dominant markers and null alleles. Molecular Ecology Notes, 7, 574–578.Google Scholar
Groleau, P., Joober, R., Israel, M., Zeramdini, N., DeGuzman, R., & Steiger, H. (2014). Methylation of the dopamine D2 receptor (DRD2) gene promoter in women with bulimia-spectrum disorder: Associations with borderline personality disorder and exposure to childhood abuse. Journal of Psychiatric Research, 48, 121–127.CrossRefGoogle ScholarPubMed
Hubisz, M. J., Falush, D., Stephens, M., & Pritchard, J. K. (2009). Inferring weak population structure with the assistance of sample group information. Molecular Ecology Resources, 9, 1322–1332. doi:10.1111/j.1755-0998.2009.02591.x Google Scholar
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., et al. (2013). Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions. Nature Neuroscience, 16, 33–41. doi:10.1038/nn.3275 Google Scholar
Lai, C. Q., Tucker, K. L., Choudhry, S., Parnell, L. D., Mattei, J., García-Bailo, B., et al. (2009). Population admixture associated with disease prevalence in the Boston Puerto Rican health study. Human Genetics, 125, 199–209.Google Scholar
Manly, J. T. (2005). Advances in research definitions of child maltreatment. Child Abuse and Neglect, 29, 425–439.CrossRefGoogle Scholar
Masten, A. S., & Cicchetti, D. (2010). Developmental cascades. Development and Psychopathology, 22, 491–495.Google Scholar
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342–348.Google Scholar
Mill, J. (2011). Epigenetic effects of gene function and their role in mediating gene–environment interactions. In Kendler, K. S., Jaffee, S. R., & Romer, D. (Eds.), The dynamic genome and mental health: The role of genes and environments in youth development (pp. 145–171). New York: Oxford University Press.Google Scholar
Monk, C., Spicer, J., & Champagne, F. A. (2012). Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways. Development and Psychopathology, 24, 1361–1376. doi:10.1017/S0954579412000764 Google Scholar
Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., et al. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: A link with the severity and type of trauma. Translational Psychiatry, 1, e59.Google Scholar
Raykan, V. K., Down, T. A., Balding, D. J., & Peck, S. (2011). Epigenome-wide association studies for common human diseases. Nature Reviews Genetics, 12, 529–541.Google Scholar
Roth, T. L. (2013). Epigenetic mechanisms in the development of behavior: Advances, challenges, and future promises of a new field. Development and Psychopathology, 25, 1279–1291. doi:10.1017/S0954579413000618 Google Scholar
Samochowiec, J., Samochowiec, A., Puls, I., Bienkowski, P., & Schott, B. H. (2014). Genetics of alcohol dependence: A review of clinical studies. Neuropsychobiology, 70, 77–94.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
Smith, C. A., & Thornberry, T. (1995). The relationship between child maltreatment and adolescent involvement in delinquency. Criminology, 33, 451–481.Google Scholar
Suderman, M., Borghol, N., Pappas, J. J., Pereira, S. M. P., Pembrey, M., Hertzman, C., et al. (2014). Childhood abuse is associated with methylation of multiple loci in adult DNA. BMC Medical Genomics, 7, 1.Google Scholar
Szyf, M., & Bick, J. (2013). DNA methylation: A mechanism for embedding early life experiences in the genome. Child Development, 84, 49–57. doi:10.1111/j.1467-8624.2012.01793.x Google Scholar
Toth, S. L., Gravener-Davis, J. A., Guild, D. J., & Cicchetti, D. (2013). Relational interventions for child maltreatment: Past, present, and future perspectives. Development and Psychopathology, 25, 1601–1617. doi:10.1017/s0954579413000795 Google Scholar
Toth, S. L., Sturge-Apple, M. L., Rogosch, F. A., & Cicchetti, D. (2015). Mechanisms of change: Testing how preventative interventions impact psychological and physiological stress functioning in mothers in neglectful families. Development and Psychopathology, 27, 1661–1674.Google Scholar
Vachon, D. D., Krueger, R. F., Rogosch, F. A., & Cicchetti, D. (2015). Assessment of the harmful psychiatric and behavioral effects of different forms of child maltreatment. JAMA Psychiatry, 72, 1135–1142. doi: 10.1001/jamapsychiatry.2015.1792 Google Scholar
van der Knaap, L. J., Hudziak, J. J., Verbiest, M. M. P. J., Verhulst, F. C., Oldehinkel, A. J., & van Oort, F. V. A. (2014). Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence: The TRAILS study. Translational Psychiatry, 4, 1–7.Google Scholar
Weder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., et al. (2014). Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. Journal of the American Academy of Child & Adolescent Psychiatry, 53, 417–424.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, and Prevention, 17, 1329–1338.Google Scholar
Yang, B. Z. Y., Zhang, H., Ge, W., Weder, N., Douglas-Palumberi, H, Perepletchikova, F., et al. (2013). Child abuse and epigenetic mechanisms of disease risk. American Journal of Preventive Medicine, 44, 101–107.Google Scholar