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

  • Oksana Yu. Naumova (a1) (a2), Maria Lee (a1), Roman Koposov (a3), Moshe Szyf (a4), Mary Dozier (a5) and Elena L. Grigorenko (a1) (a6)...
Abstract
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.

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Corresponding author
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: elena.grigorenko@yale.edu.
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P. Bateson , D. Barker , T. Clutton-Brock , D. Deb , B. D'Udine , R. A. Foley , (2004). Developmental plasticity and human health. Nature, 430, 419421.

C. Caldji , D. Francis , S. Sharma , P. M. Plotsky , & M. J Meaney . (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, 219229.

F. A. Champagne , & J. P Curley . (2005). How social experiences influence the brain. Current Opinion in Neurobiology, 15, 704709.

F. A. Champagne , J. Diorio , S. Sharma , & M. J Meaney . (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, 1273612741.

F. A. Champagne , I. C. Weaver , J. Diorio , S. Sharma , & M. J Meaney . (2003). Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area. Endocrinology, 144, 47204724.

E. Chudin , S. Kruglyak , S. C. Baker , S. Oeser , D. Barker , & T. K McDaniel . (2006). A model of technical variation of microarray signals. Journal of Computational Biology, 13, 9961003.

D Cicchetti . (2002). The impact of social experience on neurobiological systems: Illustration from a constructivist view of child maltreatment. Cognitive Development, 17, 14071428.

M. Dozier , M. Manni , M. K. Gordon , E. Peloso , M. R. Gunnar , K. C. Stovall-McClough , (2006). Foster children's diurnal production of cortisol: An exploratory study. Child Maltreatment, 11, 189197.

L. Enthoven , E. R. de Kloet , & M. S Oitzl . (2008). Effects of maternal deprivation of CD1 mice on performance in the water maze and swim stress. Behavioural Brain Research, 187, 195199.

D. Francis , J. Diorio , D. Liu , & M. J Meaney . (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 286, 11551158.

T. B. Franklin , H. Russig , I. C. Weiss , J. Gräff , N. Linder , A. Michalon , (2010). Epigenetic transmission of the impact of early stress across generations. Biological Psychiatry, 68, 408415.

V. H. Gilad , J. M. Rabey , Y. Eliyayev , & G. M Gilad . (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, 255259.

J. M. Gorman , J. M. Kent , G. M. Sullivan , & J. D Coplan . (2000). Neuroanatomical hypothesis of panic disorder revised. American Journal of Psychiatry, 157, 493505.

G Gottlieb . (1998). Normally occurring environmental and behavioral influences on gene activity: From central dogma to probabilistic epigenesis. Psychological Reviews, 105, 792892.

M. S. Grubb , & I. D Thompson . (2004). The influence of early experience on the development of sensory systems. Current Opinion in Neurobiology, 14, 503512.

K. Harkonmäki , K. Korkeila , J. Vahtera , M. Kivimäki , S. Suominen , L. Sillanmäki , (2007). Childhood adversities as a predictor of disability retirement. Journal of Epidemiology and Community Health, 61, 479484.

C. Heim , D. J. Newport , T. Mletzko , A. H. Miller , & C. B Nemeroff . (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33, 693710.

C Hertzman . (1999). The biological embedding of early experience and its effects on health in adulthood. Annals of New York Academy of Sciences, 896, 8595.

C. Hertzman , & T Boyce . (2010). How experience gets under the skin to create gradients in developmental health. Annual Review of Public Health, 31, 329347.

D. W. Huang , B. T. Sherman , & R. A Lempicki . (2009). Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Research, 37, 113.

F. Juffer , & M. H van IJzendoorn . (2005). Behavior problems and mental health referrals of international adoptees: A meta-analysis. Journal of the American Medical Association, 293, 25012515.

M. M. Kishiyama , W. T. Boyce , A. M. Jimenez , L. M. Perry , & R. T Knight . (2009). Socioeconomic disparities affect prefrontal function in children. Journal of Cognitive Neuroscience, 21, 11061115.

J. M. Kreppner , M. Rutter , C. Beckett , J. Castle , E. Colvert , C. Groothues , (2007). Normality and impairment following profound early institutional deprivation: A longitudinal follow-up into early adolescence. Developmental Psychology, 43, 931946.

S. Kriaucionis , & N Heintz . (2009). The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science, 324, 929930.

C. O. Ladd , R. L. Huot , K. V. Thrivikraman , C. B. Nemeroff , M. J. Meaney , & P. M Plotsky . (2000). Long-term behavioral and neuroendocrine adaptations to adverse early experience. Progress in Brain Research, 122, 81103.

B. S McEwen . (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, 174185.

B. S McEwen . (2008b). Understanding the potency of stressful early life experiences on brain and body function. Metabolism: Clinical & Experimental, 57, S11S15.

P. O. McGowan , A. Sasaki , A. C. D'Alessio , S. Dymov , B. Labonte , M. Szyf , (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342348.

P. O. McGowan , A. Sasaki , T. C. T. Huang , A. Unterberger , M. Suderman , C. Ernst , (2008). Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS ONE, 3, e2085.

M. J Meaney . (2001a). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 11611192.

M. J Meaney . (2011). Epigenetics and the biological definition of gene environment interactions. Child Development, 81, 4179.

M. J. Meaney , J. Diorio , D. Francis , J. Widdowson , P. LaPlanta , C. Caldji , (1996). Early environmental regulation of forebrain glucocorticoid receptor gene expression: Implications for adrenocortical responses to stress. Developmental Neuroscience, 18, 4972.

M. J. Meaney , & M Szyf . (2005). Maternal effects as a model for environmentally-dependent chromatin plasticity. Trends in Neuroscience, 28, 456463.

M. J. Meaney , M. Szyf , & J. R Seckl . (2007). Epigenetic mechanisms of perinatal programming of hypothalamic–pituitary–adrenal function and health. Trends in Molecular Medicine, 13, 269277.

C. Murgatroyd , A. V. Patchev , Y. Wu , V. Micale , Y. Bockmühl , D. Fischer , (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12, 15591566.

C. A. Nelson III, C. H. Zeanah , N. A. Fox , P. J. Marshall , A. T. Smyke , & D Guthrie . (2007). Cognitive recovery in socially deprived young children: The Bucharest Early Intervention Project. Science, 318, 19371940.

T. G. O'Connor , M. Rutter , & 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, 703712.

T. F. Oberlander , J. Weinberg , M. Papsdorf , R. Grunau , S. Virsi , & A. M Devlin . (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97106.

A Razin . (1998). CpG methylation, chromatin structure and gene silencing—A three-way connection. EMBO Journal, 17, 49054908.

M. Rutter , E. Colvert , J. Kreppner , C. Beckett , J. Castle , C. Groothues , (2007). Early adolescent outcomes for institutionally-deprived and non-deprived adoptees. I: Disinhibited attachment. Journal of Child Psychology and Psychiatry, 48, 1730.

M. J. Sabatini , P. Ebert , D. A. Lewis , P. Levitt , J. L. Cameron , & K Mirnics . (2007). Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation. Journal of Neuroscience, 27, 32953304.

T. Schlinzig , S. Johansson , A. Gunnar , T. J. Ekström , & M Norman . (2009). Epigenetic modulation at birth—Altered DNA-methylation in white blood cells after Caesarean section. Acta Pædiatrica, 98, 10961099.

T. C Schneirla . (1966). Behavioral development and comparative psychology. Quarterly Review of Biology, 41, 283302.

B. Seay , B. K. Alexander , & H. F Harlow . (1964). Maternal behavior of socially deprived Rhesus monkeys. Journal of Abnormal Psychology, 69, 345354.

A. Sfoggia , M. A. Pacheco , & R Grassi-Oliveira . (2008). History of childhood abuse and neglect and suicidal behavior at hospital admission. Crisis: Journal of Crisis Intervention & Suicide, 29, 154158.

S. J. Suomi , H. F. Harlow , & S. D Kimball . (1971). Behavioral effects of prolonged partial social isolation in the rhesus monkey. Psycholological Reports, 29, 11711177.

M Szyf . (2009). Epigenetics, DNA methylation, and chromatin modifying drugs. Annual Review of Pharmacology & Toxicology, 49, 243263.

C. Thomas , E. Hyppönen , & C Power . (2008). Obesity and type 2 diabetes risk in midadult life: The role of childhood adversity. Pediatrics, 121, e1240e1249.

M. H. van IJzendoorn , & F Juffer . (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, 12281245.

K. J. F. Verhoeven , J. J. Jansen , P. J. vanDij , & A Biere . (2010). Stress-induced DNA methylation changes and their heritability in asexual dandelions. New Phytologist, 185, 11081118.

R. A. Waterland , J. R. Lin , C. A. Smith , & R. L Jirtle . (2006). Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Human Molecular Genetics, 15, 705716.

I. C. Weaver , N. Cervoni , F. A. Champagne , A. C. D'Alessio , S. Sharma , J. R. Seckl , (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847854.

S. H Zeisel . (2009). Epigenetic mechanisms for nutrition determinants of later health outcomes. American Journal of Clinical Nutrition, 89, 1488S1493S.

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