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Childhood adversity and DNA methylation of genes involved in the hypothalamus–pituitary–adrenal axis and immune system: Whole-genome and candidate-gene associations

Published online by Cambridge University Press:  15 October 2012

Johanna Bick ,
Oksana Naumova ,
Scott Hunter ,
Baptiste Barbot ,
Maria Lee ,
Suniya S. Luthar ,
Adam Raefski  and
Elena L. Grigorenko
Johanna Bick
Affiliation:
Yale University
Oksana Naumova
Affiliation:
Yale University Vavilov Institute of General Genetics
Scott Hunter
Affiliation:
Yale University
Baptiste Barbot
Affiliation:
Yale University
Maria Lee
Affiliation:
Yale University
Suniya S. Luthar
Affiliation:
Yale University Columbia University
Adam Raefski
Affiliation:
Yale University
Elena L. Grigorenko*
Affiliation:
Yale University Columbia 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; E-mail: elena.grigorenko@yale.edu.
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Abstract

In recent years, translational research involving humans and animals has uncovered biological and physiological pathways that explain associations between early adverse circumstances and long-term mental and physical health outcomes. In this article, we summarize the human and animal literature demonstrating that epigenetic alterations in key biological systems, the hypothalamus–pituitary–adrenal axis and immune system, may underlie such disparities. We review evidence suggesting that changes in DNA methylation profiles of the genome may be responsible for the alterations in hypothalamus–pituitary–adrenal axis and immune system trajectories. Using some preliminary data, we demonstrate how explorations of genome-wide and candidate-gene DNA methylation profiles may inform hypotheses and guide future research efforts in these areas. We conclude our article by discussing the many important future directions, merging perspectives from developmental psychology, molecular genetics, neuroendocrinology, and immunology, that are essential for furthering our understanding of how early adverse circumstances may shape developmental trajectories, particularly in the areas of stress reactivity and physical or mental health.

Type
Articles
Information
Development and Psychopathology , Volume 24 , Issue 4: Contributions of the Genetic/Genomic Sciences to Developmental Psychopathology , November 2012 , pp. 1417 - 1425
Copyright
Copyright © Cambridge University Press 2012

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References

Amos, W., Driscoll, E., & Hoffman, J. (2011). Candidate genes versus genome-wide associations: Which are better for detecting genetic susceptibility to infectious disease? Proceedings of Biological Science, 278, 1183–1188.Google Scholar
Anda, R. F., Brown, D. W., Dube, S. R., Bremner, J. D., Felitti, V. J., & Giles, W. H. (2009). Adverse childhood experiences and chronic obstructive pulmonary disease in adults. American Journal of Prevention Medicine, 34, 396–403.CrossRefGoogle Scholar
Bergmann, A., & Lane, M. E. (2003). Hidden targets of microRNAs for growth control. Trends in Biochemical Sciences, 28, 461–463.Google Scholar
Borghol, N., Suderman, M., McArdle, W., Racine, A., Hallett, M., Pembrey, M., et al. (2012). Associations with early-life socio-economic position in adult DNA methylation. International Journal of Epidemiology, 41, 62–74.Google Scholar
Calandra, T., Bernhagen, J., Metz, C. N., Spiegel, L., Bacher, M., Donnely, T., et al. (1995). MIF as a glucocorticoid-induced modulator of cytokine production. Nature, 377, 68–71.CrossRefGoogle ScholarPubMed
Carpenter, L. L., Carvalho, J. P., Tyrka, A. R., Wier, L. M., Mello, A. F., Mello, M. F., et al. (2007). Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biological Psychiatry, 62, 1080–1087.CrossRefGoogle ScholarPubMed
Carpenter, L. L., Tyrka, A. R., Ross, N. S., Khoury, L., Anderson, G. M., & Price, L. H. (2009). Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biological Psychiatry, 66, 69–75.Google Scholar
Carroll, J. E., Cohen, S., & Marsland, A. L. (2011). Early childhood socioeconomic status is associated with circulating interleukin-6 among mid-life adults. Brain, Behavior, and Immunology, 7, 1468–1474.Google Scholar
Ceccatelli, S., Tamm, C., Zhang, Q., & Chen, M. (2007). Mechanisms and modulation of neural cell damage induced by oxidative stress. Physiology & Behavior, 92, 87–92.Google Scholar
Champagne, F. A., Weaver, I. C., Diorio, J., Dymov, S., Szyf, M., & Meaney, M. J. (2006). Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology, 147, 2909–2915.CrossRefGoogle ScholarPubMed
Chen, E. E., Miller, G. E., Kobor, M. S., & Cole, S. W. (2011). Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood. Molecular Psychiatry, 16, 729–737.CrossRefGoogle ScholarPubMed
Cicchetti, D., Rogosch, F. A., Gunnar, M. R., & Toth, S. L. (2010). The differential impacts of early physical and sexual abuse and internalizing problems on daytime cortisol rhythm in school-aged children. Child Development, 81, 252–269.CrossRefGoogle ScholarPubMed
Cicchetti, D., Rogosch, F. A., & Oshri, A. (2011). Interactive effects of corticotropin releasing hormone receptor 1, serotonin transporter linked polymorphic region, and child maltreatment on diurnal cortisol regulation and internalizing symptomatology. Development and Psychopathology, 23, 1125–1138.Google Scholar
Comb, M., & Goodman, H. M. (1990). CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Research, 18, 3975–3982.Google Scholar
Danese, A., Moffitt, T., Pariante, C., Ambler, A., Poulton, R., & Caspi, A. (2008). Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Archives of General Psychiatry, 65, 409–416.Google Scholar
Danese, A., Pariante, C., Caspi, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences, 104, 1319–1324.Google Scholar
De Bellis, M. D., Chrousos, G. P., Dorn, L. D., Burke, L., Helmers, K., Kling, M. A., et al. (1994). Hypothalamic–pituitary–adrenal axis dysregulation in sexually abused girls. Journal of Clinical Endocrinology and Metabolism, 78, 249–255.Google Scholar
Dozier, M., Manni, M., Gordon, M., Peloso, E., Gunnar, M. R., Stovall-McClough, K., et al. (2006). Foster children's diurnal production of cortisol: An exploratory study. Child Maltreatment, 11, 189–197.CrossRefGoogle ScholarPubMed
Drury, S., Theall, K., Gleason, M. M., Smyke, A. T., De Vivo, I., Wong, J. Y., et al. (2012). Telomere length and early severe social deprivation: Linking early adversity and cellular aging. Molecular Psychiatry, 17, 719–727.Google Scholar
Dube, S. R., Fairweather, D., Pearson, W. S., Felitti, V. J., Anda, R. F., & Croft, J. B. (2009). Cumulative childhood stress and autoimmune diseases in adults. Psychosomatic Medicine, 71, 243–250.CrossRefGoogle ScholarPubMed
Duman, R. S. (2009). Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: Stress and depression. Dialogues in Clinical Neuroscience, 11, 239–255.CrossRefGoogle ScholarPubMed
Epel, E. S. (2009). Psychological and metabolic stress: A recipe for accelerated cellular aging? Hormones, 8, 7–22.CrossRefGoogle ScholarPubMed
Essex, M. J., Shirtcliff, E. A., Burk, L. R., Ruttle, P. L., Klein, M. H., Slattery, M. J., et al. (2011). Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence. Development and Psychopathology, 23, 1039–1058.Google Scholar
Fitzpatrick, A., Kronmal, R., Gardner, J., Pstay, B., Jenny, N., Tracy, R., et al. (2007). Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. American Journal of Epidemiology, 165, 14–21.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
Gill, J. M., Saligan, L., Woods, S., & Page, G. (2009). PTSD is associated with an excess of inflammatory immune activities. Perspectives in Psychiatric Care, 45, 262–277.Google Scholar
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008). Effect of in-utero and early-life conditions on adult health and disease. New England Journal of Medicine, 359, 61–73.CrossRefGoogle ScholarPubMed
Goodwin, R. D., & Stein, M. B. (2004). Association between childhood trauma and physical disorders among adults in the United States. Psychological Medicine, 34, 509–520.CrossRefGoogle ScholarPubMed
Gunnar, M., & Donzella, B. (2002). Social regulation of the cortisol levels in early human development. Psychoneuroendocrinology, 27, 199–220.Google Scholar
Heim, C., Newport, 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
Hirschhorn, J., & Daly, M. (2005). Genome-wide association studies for common diseases and complex traits. Nature Reviews Genetics, 6, 95–108.Google Scholar
Huang, D. W., Sherman, B., & Lempicki, R. (2009). Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Research, 37, 1–13.Google Scholar
Inamdar, N. M., Ehrlich, K. C., & Ehrlich, M. (1991). CpG methylation inhibits binding of several sequence-specific DNA-binding proteins from pea, wheat, soybean and cauliflower. Plant Molecular Biology, 17, 111–123.Google Scholar
Jenuwein, T., & Allis, C. D. (2001). Translating the histone code. Science, 293, 1074–1080.CrossRefGoogle ScholarPubMed
Jin, S. G., Wu, X., Li, A. X., & Pfeifer, G. P. (2011). Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Research, 39, 5015–5024.CrossRefGoogle ScholarPubMed
Keinan-Boker, L., Vin-Raviv, N., Lipshitz, I., Linn, S., & Barchana, M. (2009). Cancer incidence in Israeli Jewish survivors of World War II. Journal of National Cancer Institute, 101, 1489–1500.CrossRefGoogle ScholarPubMed
Kendler, K. (2005). “A gene for . . .”: The nature of gene action in psychiatric disorders. American Journal of Psychiatry, 162, 1243–1252.Google Scholar
Kittleson, M. M., Meoni, L. A., Wang, N. Y., Chu, A. Y., Ford, D. E., & Klag, M. J. (2006). Association of childhood socioeconomic status with subsequent coronary heart disease in physicians. Archives of Internal Medicine, 166, 2356–2361.Google Scholar
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
Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., et al. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science, 277, 1659–1662.Google Scholar
Luthar, S., & Sexton, C. (2007). Maternal drug abuse versus maternal depression: Vulnerability and resilience among school-age and adolescent offspring. Development and Psychopathology, 19, 205–225.Google Scholar
Matthews, K. A., & Gallo, L. C. (2011). Psychological perspectives on pathways linking socioeconomic status and physical health. Annual Review of Psychology, 62, 501–530.Google Scholar
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ionnidis, J. P., et al. (2008). Genome-wide association studies for complex traits: Consensus, uncertainty and challenges. Nature Review Genetics, 9, 356–369.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
McGowan, P. O., Suderman, M., Sasaki, A., Huang, T. C., Hallett, M., Meaney, M. J., et al. (2011). Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One, 6, e14739.CrossRefGoogle ScholarPubMed
Miller, G., & Chen, E. (2007). Unfavorable socioeconomic conditions in early life presage expression of proinflammatory phenotype in adolescence. Psychosomatic Medicine, 69, 402–409.Google Scholar
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., et al. (2009). Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proceedings of the National Academy of Science, 106, 14716–14721.Google Scholar
Miller, G., Chen, E., & Parker, K. J. (2011). Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms. Psychological Bulletin, 137, 959–997.Google Scholar
Naumova, O., Lee, M., Koposov, R., Szyf, M., Dozier, M., & Grigorenko, E. L. (2012). Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Development and Psychopathology, 24, 143–155.CrossRefGoogle ScholarPubMed
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, 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.Google Scholar
Pace, T. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., et al. (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. American Journal of Psychiatry, 163, 1630–1633.Google Scholar
Perroud, N., Paoloni-Giacobino, A., Olie, P., Salzmann, A., Nicastro, R., Guillaume, S., 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.CrossRefGoogle ScholarPubMed
Phillips, J. E., Marsland, A. L., Flory, J. D., & Muldoon, M. F. (2009). Parental education is related to C-reactive protein among female middle-aged community volunteers. Brain, Behavior, and Immunology, 23, 677–683.CrossRefGoogle ScholarPubMed
Pollitt, R. A., Kaufman, J. S., Rose, K. M., Diez-Roux, A.V., Zeng, D., & Heiss, G. (2007). Early-life and adult socioeconomic status and inflammatory risk markers in adulthood. European Journal of Epidemiology, 22, 55–66.CrossRefGoogle ScholarPubMed
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., et al. (2011). Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry, 1, 1–6.Google Scholar
Rich-Edwards, J. W., Spiegelman, D., Hibert, E., Jun, H., Todd, T., Kawachi, I., et al. (2010). Abuse in childhood and adolescence as a predictor of type 2 diabetes in adult women. American Journal of Preventive Medicine, 39, 529–536.CrossRefGoogle ScholarPubMed
Riley, E. H., Wright, R. J., Jun, H. J., Hibert, E. N., & Rich-Edwards, J. W. (2010). Hypertension in adult survivors of child abuse: Observations from the Nurses' Health Study II. Journal of Epidemiology and Community Health, 64, 413–418.Google Scholar
Rohner, R. P. (1991). Handbook for the study of parental acceptance and rejection. Storrs, CT: University of Connecticut, Center for the Study of Parental Acceptance and Rejection.Google Scholar
Schulze, T. G., & McMahon, F. J. (2002). Genetic association mapping at the crossroads: Which test and why? Overview and practical guidelines. American Journal Medical Genetics, 114, 1–11.Google Scholar
Segman, R. H., Shefi, N. N., Goltser-Dubner, T. T., Friedman, N. N., Kaminski, N. N., & Shalev, A. Y. (2005). Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Molecular Psychiatry, 10, 500–513.CrossRefGoogle ScholarPubMed
Shalev, I., Moffit, T., Sugden, K., Williams, B., Houts, R., Danese, A., et al. (2012). Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: A longitudinal study. Molecular Psychiatry. Advance online publication. doi:10.1038/mp.2012.32Google ScholarPubMed
Shirtcliff, E. A., Coe, C. L., & Pollak, S. D. (2009). Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1. Proceedings of the National Academy of Sciences, 106, 2963–2967.Google Scholar
Shonkoff, J. P., Boyce, W., & McEwen, B. S. (2009). Neuroscience, molecular biology, and the childhood roots of health disparities building a new framework for health promotion and disease prevention. Journal of the American Medical Association, 301, 2252–2259.Google Scholar
Simon, N. M., Smoller, J. W., McNamara, K. L., Maser, R. S., Zalta, A. K., Pollack, M. H., et al. (2006). Telomere shortening and mood disorders: Preliminary support for a chronic stress model of accelerated aging. Biological Psychiatry, 60, 432–435.CrossRefGoogle ScholarPubMed
Smith, A. K., Conneely, K. N., Kilaru, V., Mercer, K. B., Weiss, T. E., Bradley-Davino, B., et al. (2011). Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. American Journal of Medical Genetics, 156B, 700–708.Google Scholar
Strahl, B. D., & Allis, C. D. (2000). The language of covalent histone modifications. Nature, 403, 41–45.Google Scholar
Taylor, S. E., Lehman, B. J., Kiefe, C. I., & Seeman, T. E. (2006). Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study. Biological Psychiatry, 60, 819–824.CrossRefGoogle ScholarPubMed
Taylor, S. E., Lerner, J. S., Sage, R. M., Lehman, B. J., & Seeman, T. E. (2004), Early environment, emotions, responses to stress, and health. Journal of Personality, 72, 1365–1394.CrossRefGoogle ScholarPubMed
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012). Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: Preliminary findings in healthy adults. PLoS One, 7, e30148.Google Scholar
Tyrka, A. R., Wier, L., Price, L. H., Ross, N., Anderson, G. M., Wilkinson, C. W., et al. (2008). Childhood parental loss and adult hypothalamic–pituitary–adrenal function. Biological Psychiatry, 63, 1147–1154.Google Scholar
Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de los Santos, R., et al. (2010). Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 107, 9470–9475.CrossRefGoogle ScholarPubMed
van der Vegt, E. M., van der Ende, J., Kirschbaum, C., Verhulst, F. C., & Tiemeier, H. (2009). Early neglect and abuse predict diurnal cortisol patterns in adults: A study of international adoptees. Psychoneuroendocrinology, 34, 660–669.Google Scholar
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
Wismer-Fries, A. B., Shirtcliff, E. A., & Pollak, S. D. (2008). Neuroendocrine dysregulation following early social deprivation in children. Developmental Psychobiology, 50, 588–599.Google Scholar
Wolkowitz, O. M., Mellon, S. H., Epel, E. S., Lin, J., Dhabhar, F. S., Su, Y., et al. (2011). Leukocyte telomere length in major depression: Correlations with chronicity, inflammation and oxidative stress—Preliminary findings. PLoS One, 6, e17837.CrossRefGoogle ScholarPubMed
Yoo, Y. J., Bull, S. B., Paterson, A. D., Waggott, D., Sun, L., & The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. (2010). Were genome-wide linkage studies a waste of time? Exploiting candidate regions within genome-wide association studies. Genetic Epidemiology, 34, 107–118.Google Scholar
Zhu, M., & Zhao, S. (2007). Candidate gene identification approach: Progress and challenges. International Journal of Biological Science, 3, 420–427.Google Scholar
Zieker, J. J., Zieker, D. D., Jatzko, A. A., Dietzsch, J. J., Nieselt, K. K., Schmitt, A. A., et al. (2007). Differential gene expression in peripheral blood of patients suffering from post-traumatic stress disorder. Molecular Psychiatry, 12, 116–119.Google Scholar
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