Hostname: page-component-6bf8c574d5-t27h7 Total loading time: 0 Render date: 2025-02-20T12:22:03.600Z Has data issue: false hasContentIssue false
  • English
  • Français

Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents

Published online by Cambridge University Press:  29 November 2011

Oksana Yu. Naumova ,
Maria Lee ,
Roman Koposov ,
Moshe Szyf ,
Mary Dozier  and
Elena L. Grigorenko
Oksana Yu. Naumova
Affiliation:
Yale University Vavilov Institute of General Genetics RAS
Maria Lee
Affiliation:
Yale University
Roman Koposov
Affiliation:
University of Tromsø
Moshe Szyf
Affiliation:
McGill University
Mary Dozier
Affiliation:
University of Delaware
Elena L. Grigorenko*
Affiliation:
Yale University Moscow State University
*
Address correspondence and reprint requests to: Elena L. Grigorenko, Child Study Center, Yale University, 230 South Frontage Road, New Haven, CT 06519-1124; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Previous studies with nonhuman species have shown that animals exposed to early adversity show differential DNA methylation relative to comparison animals. The current study examined differential methylation among 14 children raised since birth in institutional care and 14 comparison children raised by their biological parents. Blood samples were taken from children in middle childhood. Analysis of whole-genome methylation patterns was performed using the Infinium HumanMethylation27 BeadChip assay (Illumina), which contains 27,578 CpG sites, covering approximately 14,000 gene promoters. Group differences were registered, which were characterized primarily by greater methylation in the institutionalized group relative to the comparison group, with most of these differences in genes involved in the control of immune response and cellular signaling systems, including a number of crucial players important for neural communication and brain development and functioning. The findings suggest that patterns of differential methylation seen in nonhuman species with altered maternal care are also characteristic of children who experience early maternal separation.

Type
Regular Articles
Information
Development and Psychopathology , Volume 24 , Issue 1 , February 2012 , pp. 143 - 155
Copyright
Copyright © Cambridge University Press 2012

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

Alvazian, S. A., & Kolenikov, S. O. (2000). Poverty and expenditure differentiation of Russian population. Final Report. Moscow, Russia: Economics Education and Research Consortium Russia. Retrieved from www.komkon.org/~tacik/science/Aivazian-Kolenikov-FinalEng-2.pdfGoogle Scholar
Bateson, P., Barker, D., Clutton-Brock, T., Deb, D., D'Udine, B., Foley, R. A., et al. (2004). Developmental plasticity and human health. Nature, 430, 419–421.CrossRefGoogle ScholarPubMed
Caldji, C., Francis, D., Sharma, S., Plotsky, P. M., & Meaney, M. J. (2000). The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neuropsychopharmacology, 22, 219–229.CrossRefGoogle ScholarPubMed
Champagne, F. A., & Curley, J. P. (2005). How social experiences influence the brain. Current Opinion in Neurobiology, 15, 704–709.CrossRefGoogle ScholarPubMed
Champagne, F. A., Diorio, J., Sharma, S., & Meaney, M. J. (2001). Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences of the United States of America, 98, 12736–12741.CrossRefGoogle ScholarPubMed
Champagne, F. A., Weaver, I. C., Diorio, J., Sharma, S., & Meaney, M. J. (2003). Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area. Endocrinology, 144, 4720–4724.CrossRefGoogle ScholarPubMed
Chudin, E., Kruglyak, S., Baker, S. C., Oeser, S., Barker, D., & McDaniel, T. K. (2006). A model of technical variation of microarray signals. Journal of Computational Biology, 13, 996–1003.CrossRefGoogle Scholar
Cicchetti, D. (2002). The impact of social experience on neurobiological systems: Illustration from a constructivist view of child maltreatment. Cognitive Development, 17, 1407–1428.CrossRefGoogle 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.CrossRefGoogle Scholar
Cooney, C. A., Dave, A. A., & Wolff, G. L. (2002). Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. Journal of Nutrition, 132, 2393–2400.CrossRefGoogle ScholarPubMed
Dozier, M., Manni, M., Gordon, M. K., Peloso, E., Gunnar, M. R., Stovall-McClough, K. C., et al. (2006). Foster children's diurnal production of cortisol: An exploratory study. Child Maltreatment, 11, 189–197.CrossRefGoogle ScholarPubMed
Enthoven, L., de Kloet, E. R., & Oitzl, M. S. (2008). Effects of maternal deprivation of CD1 mice on performance in the water maze and swim stress. Behavioural Brain Research, 187, 195–199.CrossRefGoogle ScholarPubMed
Essex, M. J., Boyce, W. T., Hertzman, C., Lam, L., Armstrong, J. M., Neumann, S. M. A., et al. (in press). Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Development.Google Scholar
Francis, D., Diorio, J., Liu, D., & Meaney, M. J. (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 286, 1155–1158.CrossRefGoogle ScholarPubMed
Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry, 68, 408–415.CrossRefGoogle Scholar
Gilad, V. H., Rabey, J. M., Eliyayev, Y., & Gilad, G. M. (2000). Different effects of acute neonatal stressors and long-term postnatal handling on stress-induced changes in behavior and in ornithine decarboxylase activity of adult rats. Brain Research. Developmental Brain Research, 120, 255–259.CrossRefGoogle ScholarPubMed
Gorman, J. M., Kent, J. M., Sullivan, G. M., & Coplan, J. D. (2000). Neuroanatomical hypothesis of panic disorder revised. American Journal of Psychiatry, 157, 493–505.CrossRefGoogle ScholarPubMed
Gottlieb, G. (1998). Normally occurring environmental and behavioral influences on gene activity: From central dogma to probabilistic epigenesis. Psychological Reviews, 105, 792–892.CrossRefGoogle ScholarPubMed
Grubb, M. S., & Thompson, I. D. (2004). The influence of early experience on the development of sensory systems. Current Opinion in Neurobiology, 14, 503–512.CrossRefGoogle ScholarPubMed
Gunnar, M. R., & Fisher, P. A. (2006). Early experience, stress, and prevention network. Bringing basic research on early experience and stress neurobiology to bear on preventive interventions for neglected and maltreated children. Development and Psychopathology, 18, 651–677.CrossRefGoogle ScholarPubMed
Gunnar, M. R., Van Dulmen, M. H. M., & The International Adoption Project Team. (2007). Behavior problems in post-institutionalized internationally adopted children. Development and Psychopathology, 19, 129–148.CrossRefGoogle Scholar
Harkonmäki, K., Korkeila, K., Vahtera, J., Kivimäki, M., Suominen, S., Sillanmäki, L., et al. (2007). Childhood adversities as a predictor of disability retirement. Journal of Epidemiology and Community Health, 61, 479–484.CrossRefGoogle ScholarPubMed
Heim, C., Newport, D. J., 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.CrossRefGoogle ScholarPubMed
Heinrichs, S. C., & Koob, G. F. (2006). Application of experimental stressors in laboratory rodents Current Protocols in Neuroscience, Chap. 8, Unit 8.4.Google Scholar
Hertzman, C. (1999). The biological embedding of early experience and its effects on health in adulthood. Annals of New York Academy of Sciences, 896, 85–95.CrossRefGoogle ScholarPubMed
Hertzman, C., & Boyce, T. (2010). How experience gets under the skin to create gradients in developmental health. Annual Review of Public Health, 31, 329–347.CrossRefGoogle ScholarPubMed
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009). Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Research, 37, 1–13.CrossRefGoogle ScholarPubMed
Juffer, F., & van IJzendoorn, M. H. (2005). Behavior problems and mental health referrals of international adoptees: A meta-analysis. Journal of the American Medical Association, 293, 2501–2515.CrossRefGoogle ScholarPubMed
Kishiyama, M. M., Boyce, W. T., Jimenez, A. M., Perry, L. M., & Knight, R. T. (2009). Socioeconomic disparities affect prefrontal function in children. Journal of Cognitive Neuroscience, 21, 1106–1115.CrossRefGoogle ScholarPubMed
Kreppner, J. M., Rutter, M., Beckett, C., Castle, J., Colvert, E., Groothues, C., et al. (2007). Normality and impairment following profound early institutional deprivation: A longitudinal follow-up into early adolescence. Developmental Psychology, 43, 931–946.CrossRefGoogle ScholarPubMed
Kriaucionis, S., & Heintz, N. (2009). The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science, 324, 929–930.CrossRefGoogle ScholarPubMed
Ladd, C. O., Huot, R. L., Thrivikraman, K. V., Nemeroff, C. B., Meaney, M. J., & Plotsky, P. M. (2000). Long-term behavioral and neuroendocrine adaptations to adverse early experience. Progress in Brain Research, 122, 81–103.CrossRefGoogle ScholarPubMed
Liu, D., Diorio, J., Day, J. C., Francis, D. D., & Meaney, M. J. (2000). Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nature Neuroscience, 3, 799–806.CrossRefGoogle ScholarPubMed
McEwen, B. S. (2008a). Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. European Journal of Pharmacology, 583, 174–185.CrossRefGoogle ScholarPubMed
McEwen, B. S. (2008b). Understanding the potency of stressful early life experiences on brain and body function. Metabolism: Clinical & Experimental, 57, S11–S15.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
McGowan, P. O., Sasaki, A., Huang, T. C. T., Unterberger, A., Suderman, M., Ernst, C., et al. (2008). Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS ONE, 3, e2085.CrossRefGoogle ScholarPubMed
Meaney, M. J. (2001a). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161–1192.CrossRefGoogle Scholar
Meaney, M. J. (2001b). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161–1192.CrossRefGoogle Scholar
Meaney, M. J. (2011). Epigenetics and the biological definition of gene environment interactions. Child Development, 81, 41–79.CrossRefGoogle Scholar
Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlanta, P., Caldji, C., et al. (1996). Early environmental regulation of forebrain glucocorticoid receptor gene expression: Implications for adrenocortical responses to stress. Developmental Neuroscience, 18, 49–72.CrossRefGoogle ScholarPubMed
Meaney, M. J., & Szyf, M. (2005). Maternal effects as a model for environmentally-dependent chromatin plasticity. Trends in Neuroscience, 28, 456–463.CrossRefGoogle Scholar
Meaney, M. J., Szyf, M., & Seckl, J. R. (2007). Epigenetic mechanisms of perinatal programming of hypothalamic–pituitary–adrenal function and health. Trends in Molecular Medicine, 13, 269–277.CrossRefGoogle ScholarPubMed
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmühl, Y., Fischer, D., et al. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12, 1559–1566.CrossRefGoogle ScholarPubMed
Nelson, C. A. III, Zeanah, C. H., Fox, N. A., Marshall, P. J., Smyke, A. T., & Guthrie, D. (2007). Cognitive recovery in socially deprived young children: The Bucharest Early Intervention Project. Science, 318, 1937–1940.CrossRefGoogle ScholarPubMed
O'Connor, T. G., Rutter, M., & The English and Romanian Adoptees Study Team. (2000). Attachment disorder behaviour following early severe deprivation: Extension and longitudinal follow-up. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 703–712.CrossRefGoogle ScholarPubMed
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Virsi, S., & Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97–106.CrossRefGoogle ScholarPubMed
Razin, A. (1998). CpG methylation, chromatin structure and gene silencing—A three-way connection. EMBO Journal, 17, 4905–4908.CrossRefGoogle ScholarPubMed
Rutter, M., Colvert, E., Kreppner, J., Beckett, C., Castle, J., Groothues, C., et al. (2007). Early adolescent outcomes for institutionally-deprived and non-deprived adoptees. I: Disinhibited attachment. Journal of Child Psychology and Psychiatry, 48, 17–30.CrossRefGoogle ScholarPubMed
Sabatini, M. J., Ebert, P., Lewis, D. A., Levitt, P., Cameron, J. L., & Mirnics, K. (2007). Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation. Journal of Neuroscience, 27, 3295–3304.CrossRefGoogle ScholarPubMed
Sapogov, M. V. (2010). Правосознание и правовая социализация несовершеннолетних осужденных из числа детей-сирот и детей, оставшихся без попечения родителей. Pskov, Russia: ANO Logos.Google Scholar
Schlinzig, T., Johansson, S., Gunnar, A., Ekström, T. J., & Norman, M. (2009). Epigenetic modulation at birth—Altered DNA-methylation in white blood cells after Caesarean section. Acta Pædiatrica, 98, 1096–1099.CrossRefGoogle ScholarPubMed
Schneirla, T. C. (1966). Behavioral development and comparative psychology. Quarterly Review of Biology, 41, 283–302.CrossRefGoogle ScholarPubMed
Schwirtz, M. (2008, October 1). An experiment in orphan care in Russia, The New York Times. Retrieved from http://www.nytimes.com/2008/10/01/world/europe/01iht-russia.4.16620179.htmlGoogle Scholar
Seay, B., Alexander, B. K., & Harlow, H. F. (1964). Maternal behavior of socially deprived Rhesus monkeys. Journal of Abnormal Psychology, 69, 345–354.CrossRefGoogle ScholarPubMed
Sfoggia, A., Pacheco, M. A., & Grassi-Oliveira, R. (2008). History of childhood abuse and neglect and suicidal behavior at hospital admission. Crisis: Journal of Crisis Intervention & Suicide, 29, 154–158.CrossRefGoogle ScholarPubMed
Suomi, S. J., Harlow, H. F., & Kimball, S. D. (1971). Behavioral effects of prolonged partial social isolation in the rhesus monkey. Psycholological Reports, 29, 1171–1177.CrossRefGoogle ScholarPubMed
Szyf, M. (2009). Epigenetics, DNA methylation, and chromatin modifying drugs. Annual Review of Pharmacology & Toxicology, 49, 243–263.CrossRefGoogle ScholarPubMed
The St. Petersburg–USA Orphanage Research Team. (2008). The effects of early social–emotional and relationship experience on the development of young orphanage chidren. Monographs of the Society for Research in Child Development, 73, 1–297.Google Scholar
Thomas, C., Hyppönen, E., & Power, C. (2008). Obesity and type 2 diabetes risk in midadult life: The role of childhood adversity. Pediatrics, 121, e1240–e1249.CrossRefGoogle ScholarPubMed
van IJzendoorn, M. H., & Juffer, F. (2006). The Emanuel Miller Memorial Lecture 2006: Adoption as intervention. Meta-analytic evidence for massive catch-up and plasticity in physical, socio-emotional, and cognitive development. Journal of Child Psychology and Psychiatry, 47, 1228–1245.CrossRefGoogle Scholar
Verhoeven, K. J. F., Jansen, J. J., vanDij, P. J., & Biere, A. (2010). Stress-induced DNA methylation changes and their heritability in asexual dandelions. New Phytologist, 185, 1108–1118.CrossRefGoogle ScholarPubMed
Waterland, R. A., Lin, J. R., Smith, C. A., & Jirtle, R. L. (2006). Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Human Molecular Genetics, 15, 705–716.CrossRefGoogle ScholarPubMed
Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–854.CrossRefGoogle ScholarPubMed
Zeisel, S. H. (2009). Epigenetic mechanisms for nutrition determinants of later health outcomes. American Journal of Clinical Nutrition, 89, 1488S–1493S.CrossRefGoogle ScholarPubMed
Supplementary material: File

Yu Supplementary Tables

Yu Supplementary Tables

Download Yu Supplementary Tables(File)
File 4.9 MB