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Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment

Published online by Cambridge University Press:  22 November 2017

Justin Parent ,
Stephanie H. Parade ,
Laura E. Laumann ,
Kathryn K. Ridout ,
Bao-Zhu Yang ,
Carmen J. Marsit ,
Ronald Seifer  and
Audrey R. Tyrka
Justin Parent
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital Florida International University
Stephanie H. Parade
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Laura E. Laumann
Affiliation:
Butler Hospital
Kathryn K. Ridout
Affiliation:
Brown University Alpert Medical School Butler Hospital
Bao-Zhu Yang
Affiliation:
Yale University School of Medicine
Carmen J. Marsit
Affiliation:
Emory University
Ronald Seifer
Affiliation:
Brown University Alpert Medical School E. P. Bradley Hospital
Audrey R. Tyrka*
Affiliation:
Brown University Alpert Medical School Butler Hospital
*
Address correspondence and reprint requests to: Audrey R. Tyrka, Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, RI 02903; E-mail: [email protected].
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Abstract

Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus–pituitary–adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3–5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.

Type
Special Issue Articles
Information
Development and Psychopathology , Volume 29 , Special Issue 5: Biological and Behavioral Effects of Early Adversity on Multiple Levels of Development , December 2017 , pp. 1635 - 1648
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

This research was supported by Grant R01 MH083704 (to A.R.T.) and R25 MH101076 (K.K.R.) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIMH. We are grateful to the children and families who participated in this study, and we thank Hasbro Children's Hospital, Rhode Island Head Start, and the Rhode Island Department of Children, Youth, and Families for assisting in recruitment of study participants. We also thank Brittney Josefson and the numerous other research assistants who contributed to this project, and Asi Polly Gobin for data management. Isolation of DNA and genotyping were done in the laboratory of Joel Gelernter, MD, and we are grateful to Dr. Gelernter and his staff for their contribution.

References

Barden, N. (2004). Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. Journal of Psychiatry and Neuroscience, 29, 185–193.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
Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes & Development, 16, 6–21. doi:10.1101/gad.947102 CrossRefGoogle ScholarPubMed
Boyce, W. T., & Kobor, M. S. (2015). Development and the epigenome: The “synapse” of gene environment interplay. Developmental Science, 18, 1–23. doi:10.1111/desc.12282 Google Scholar
Braquehais, M. D., Picouto, M. D., Casas, M., & Sher, L. (2012). Hypothalamic–pituitary–adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide. World Journal of Pediatrics, 8, 197–206. doi:10.1007/s12519-012-0358-0 CrossRefGoogle ScholarPubMed
Breton, C. V., Marsit, C. J., Faustman, E., Nadeau, K., Goodrich, J. M., Dolinoy, D. C., … Yousefi, P. (2017). Small-magnitude effect sizes in epigenetic end points are important in children's environmental health studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives, 125, 511–526. doi:10.1289/EHP595 Google Scholar
Cicchetti, D., & Toth, S. L. (2016). Child maltreatment and developmental psychopathology: A multilevel perspective. In Cicchetti, D. (Ed.), Developmental psychopathology (Vol. 3, 3rd ed., pp. 457–512). Hoboken, NJ: Wiley.CrossRefGoogle ScholarPubMed
Cohen, S., Janicki-Deverts, D., & Miller, G. E. (2007). Psychological stress and disease. Journal of the American Medical Association, 298, 1685–1687. doi:10.1001/jama.298.14.1685 CrossRefGoogle ScholarPubMed
Conradt, E., Hawes, K., Guerin, D., Armstrong, D. A., Marsit, C. J., Tronick, E., & Lester, B. M. (2016). The contributions of maternal sensitivity and maternal depressive symptoms to epigenetic processes and neuroendocrine functioning. Child Development, 87, 73–85. doi:10.1111/cdev.12483 CrossRefGoogle ScholarPubMed
Conradt, E., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013). The roles of DNA methylation of NR3C1 and 11beta-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics, 8, 1321–1329. doi:10.4161/epi.26634 CrossRefGoogle ScholarPubMed
Dadds, M. R., Moul, C., Hawes, D. J., Mendoza Diaz, A., & Brennan, J. (2015). Individual differences in childhood behavior disorders associated with epigenetic modulation of the cortisol receptor gene. Child Development, 86, 1311–1320. doi:10.1111/cdev.12391 Google Scholar
Daskalakis, N. P., & Yehuda, R. (2014). Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: Systematic of contributing factors. Frontiers in Neuroscience, 8, 369. doi:10.3389/fnins.2014.00369 Google Scholar
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6, 463–475. doi:10.1038/nrn1683 Google Scholar
Doom, J. R., & Gunnar, M. R. (2013). Stress physiology and developmental psychopathology: Past, present, and future. Development and Psychopathology, 25, 1359–1373. doi:10.1017/S0954579413000667 Google Scholar
Farré, P., Jones, M. J., Meaney, M. J., Emberly, E., Turecki, G., & Kobor, M. S. (2015). Concordant and discordant DNA methylation signatures of aging in human blood and brain. Epigenetics & Chromatin, 8, 19. doi:10.1186/s13072-015-0011-y CrossRefGoogle ScholarPubMed
Heim, C., & Binder, E. B. (2012). Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Experimental Neurology, 233, 102–111. doi:10.1016/j.expneurol.2011.10.032 Google Scholar
Herman, J. P., McKlveen, J. M., Solomon, M. B., Carvalho-Netto, E., & Myers, B. (2012). Neural regulation of the stress response: Glucocorticoid feedback mechanisms. Brazilian Journal of Medical and Biological Research, 45, 292–298. doi:10.1590/S0100-879X2012007500041 CrossRefGoogle ScholarPubMed
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., … Claes, S. (2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research, 47, 880–891. doi:10.1016/j.jpsychires.2013.03.009 Google Scholar
Hu, L., & Bentler, P. (1999). Cutoff criteria for fit indices in covariance structure analysis: Conventional criteria versus new alternatives. Structural Equation Modeling, 6, 1–55. doi:10.1080/10705519909540118 Google Scholar
Jones, M. J., Moore, S. R., & Kobor, M. S. (in press). Principles and challenges of applying epigenetic epidemiology to psychology. Annual Review of Psychology.Google Scholar
Kadmiel, M., & Cidlowski, J. A. (2013). Glucocorticoid receptor signaling in health and disease. Trends in Pharmacological Sciences, 34, 518–530. doi:10.1016/j.tips.2013.07.003 Google Scholar
Kertes, D. A., Kamin, H. S., Hughes, D. A., Rodney, N. C., Bhatt, S., & Mulligan, C. J. (2016). Prenatal maternal stress predicts methylation of genes regulating the hypothalamic-pituitary-adrenocortical system in mothers and newborns in the Democratic Republic of Congo. Child Development, 87, 61–72. doi:10.1111/cdev.12487 Google Scholar
Kosten, T. A., Huang, W., & Nielsen, D. A. (2014). Sex and litter effects on anxiety and DNA methylation levels of stress and neurotrophin genes in adolescent rats. Developmental Psychobiology, 56, 392–406. doi:10.1002/dev.21106 CrossRefGoogle ScholarPubMed
Kosten, T. A., & Nielsen, D. A. (2014). Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum. International Journal of Developmental Neuroscience, 36, 5–12. doi:10.1016/j.ijdevneu.2014.03.010 Google Scholar
Kundakovic, M., Lim, S., Gudsnuk, K., & Champagne, F. A. (2013). Sex-specific and strain dependent effects of early life adversity on behavioral and epigenetic outcomes. Frontiers in Psychiatry, 4, 78.Google Scholar
Labonte, B., Azoulay, N., Yerko, V., Turecki, G., & Brunet, A. (2014). Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder. Translational Psychiatry, 4, e368. doi:10.3389/fpsyt.2013.00078 CrossRefGoogle ScholarPubMed
Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., Turecki, G. (2012). Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry, 72, 41–48. doi:10.1016/j.biopsych.2012.01.034 Google Scholar
Laryea, G., Muglia, L., Arnett, M., & Muglia, L. J. (2015). Dissection of glucocorticoid receptor mediated inhibition of the hypothalamic-pituitary-adrenal axis by gene targeting in mice. Frontiers in Neuroendocrinology, 36, 150–164. doi:10.1016/j.yfrne.2014.09.002 Google Scholar
Leenen, F. A., Muller, C. P., & Turner, J. D. (2016). DNA methylation: Conducting the orchestra from exposure to phenotype? Clinical Epigenetics, 8, 92. doi:10.1186/s13148-016-0256-8 Google Scholar
Lester, B. M., Conradt, E., & Marsit, C. (2016). Introduction to the special section on epigenetics. Child Development, 87, 29–37. doi:10.1111/cdev.12489 CrossRefGoogle Scholar
Lévesque, M. L., Casey, K. F., Szyf, M., Ismaylova, E., Ly, V., Verner, M., … Booij, L. (2014). Genomewide DNA methylation variability in adolescent monozygotic twins followed since birth. Epigenetics, 9, 1410–1421. doi:10.4161/15592294.2014.970060 Google Scholar
Lillycrop, K. A., Slater-Jefferies, J. L., Hanson, M. A., Godfrey, K. M., Jackson, A. A., & Burdge, G. C. (2007). Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. British Journal of Nutrition, 97, 1064–1073. doi:10.1017/S000711450769196X CrossRefGoogle ScholarPubMed
McArdle, J. J. (2009). Latent variable modeling of differences and changes with longitudinal data. Annual Review of Psychology, 60, 577–605. doi:10.1146/annurev.psych.60.110707.163612 Google Scholar
McCrory, E. J., & Viding, E. (2015). The theory of latent vulnerability: Reconceptualizing the link between childhood maltreatment and psychiatric disorder. Development and Psychopathology, 27, 493–505. doi:10.1017/S0954579415000115 Google Scholar
McEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N., & Nasca, C. (2015). Mechanisms of stress in the brain. Nature Neuroscience, 18, 1353–1363. doi:10.1038/nn.4086 CrossRefGoogle ScholarPubMed
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., … Menaey, M. J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342–348. doi:10.1038/nn.2270 Google Scholar
McGregor, K., Labbe, A., & Greenwood, C. M. (2017). Response to: Correcting for cell-type effects in DNA methylation studies: Reference-based method outperforms latent variable approaches in empirical studies. Genome Biology, 18, 25. doi:10.1186/s13059-017-1149-7 Google Scholar
Meaney, M. J. (2010). Epigenetics and the biological definition of Gene × Environment interactions. Child Development, 81, 41–79. doi:10.1111/j.1467-8624.2009.01381.x Google Scholar
Melas, P. A., Wei, Y., Wong, C. C., Sjoholm, L. K., Aberg, E., Mill, J., … Lavbratt, C. (2013). Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. International Journal of Neuropsychopharmacology, 16, 1513–1528. doi:10.1017/S1461145713000102 Google Scholar
Mulligan, C. J., D'Errico, N. C., Stees, J., & Hughes, D. A. (2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics, 7, 853–857. doi:10.4161/epi.21180 Google Scholar
Muthén, L. K., & Muthén, B. O. (1998–2012). Mplus user's guide (6th ed.). Los Angeles: Author.Google Scholar
Na, K. S., Chang, H. S., Won, E., Han, K. M., Choi, S., Tae, W. S., … Ham, B. J. (2014). Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLOS ONE, 9, e85425. doi:10.1371/journal.pone.0085425 CrossRefGoogle ScholarPubMed
Norman, R. E., Byambaa, M., De, R., Butchart, A., Scott, J., & Vos, T. (2012). The long-term health consequences of child physical abuse, emotional abuse, and neglect: A systematic review and meta-analysis. PLOS Medicine, 9, e1001349. doi:10.1371/journal.pmed.1001349 Google Scholar
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. doi:10.4161/epi.3.2.6034 Google Scholar
Ostlund, B. D., Conradt, E., Crowell, S. E., Tyrka, A. R., Marsit, C. J., & Lester, B. M. (2016). Prenatal stress, fearfulness, and the epigenome: Exploratory analysis of sex differences in DNA methylation of the glucocorticoid receptor gene. Frontiers in Behavioral Neuroscience. Advance online publication. doi:10.3389/fnbeh.2016.00147 Google Scholar
Palma-Gudiel, H., Cordova-Palomera, A., Leza, J. C., & Fananas, L. (2015). Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience & Biobehavioral Reviews, 55, 520–535. doi:10.1016/j.neubiorev.2015.05.016 Google Scholar
Parade, S. H., Ridout, K. K., Seifer, R., Armstrong, D. A., Marsit, C. J., McWilliams, M. A., & Tyrka, A. R. (2016). Methylation of the glucocorticoid receptor gene promoter in preschoolers: Links with internalizing behavior problems. Child Development, 87, 86–97. doi:10.1111/cdev.12484 Google Scholar
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics, 38, 904–909. doi:10.1038/ng1847 Google Scholar
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81, 559–575. doi:10.1086/519795 Google Scholar
Roberts, S., Keers, R., Lester, K. J., Coleman, J. R., Breen, G., Arendt, K., … Havik, O. E. (2015). HPA axis related genes and response to psychological therapies: Genetics and epigenetics. Depression and Anxiety, 32, 861–870. doi:10.1002/da.22430 CrossRefGoogle ScholarPubMed
Romens, S. E., McDonald, J., Svaren, J., & Pollak, S. D. (2015). Associations between early life stress and gene methylation in children. Child Development, 86, 303–309. doi:10.1111/cdev.12270 Google Scholar
Rutten, B. P. F., Vermetten, E., Vinkers, C. H., Ursini, G., Daskalakis, N. P., Pishva, E., … Kenis, G. (2017). Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder. Molecular Psychiatry. Advance online publication. doi:10.1038/mp.2017.120 Google Scholar
Scheeringa, M. S., & Haslett, N. (2010). The reliability and criterion validity of the Diagnostic Infant and Preschool Assessment: A new diagnostic instrument for young children. Child Psychiatry and Human Development, 41, 299–312. doi:10.1007/s10578-009-0169-2 Google Scholar
Shonkoff, J. P., Boyce, W. T., & 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. doi:10.1001/jama.2009.754 Google Scholar
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., … Binder, E. B. (2015). DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 168, 36–44. doi:10.1002/ajmg.b.32278 Google Scholar
Stroud, L. R., Papandonatos, G. D., Rodriguez, D., McCallum, M., Salisbury, A. L., Phipps, M. G., … Marsit, C. (2014). Maternal smoking during pregnancy and infant stress response: Test of a prenatal programming hypothesis. Psychoneuroendocrinology, 48, 29–40. doi:10.1016/j.psyneuen.2014.05.017 Google Scholar
Szyf, M. (2013). The genome- and system-wide response of DNA methylation to early life adversity and its implication on mental health. Canadian Journal of Psychiatry, 58, 697–704. doi:10.1177/070674371305801208 Google Scholar
Turecki, G., & Meaney, M. J. (2016). Effects of the social environment and stress on glucocorticoid receptor gene methylation: A systematic review. Biological Psychiatry, 79, 87–96. doi:10.1016/j.biopsych.2014.11.022 Google Scholar
Tyrka, A. R., Burgers, D. E., Philip, N. S., Price, L. H., & Carpenter, L. L. (2013). The neurobiological correlates of childhood adversity and implications for treatment. Acta Psychiatrica Scandinavica, 128, 434–447. doi:10.1111/acps.12143 Google Scholar
Tyrka, A. R., Parade, S. H., Eslinger, N. M., Marsit, C. J., Lesseur, C., Armstrong, D. A., … Seifer, R. (2015). Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in pre-school aged children. Development and Psychopathology, 27, 577–585. doi:10.1017/S0954579415000176 Google Scholar
Tyrka, A. R., Parade, S. H., Welch, E. S., Ridout, K. K., Price, L. H., Marsit, C., … Carpenter, L. L. (2016). Methylation of the leukocyte glucocorticoid receptor gene promotor in adults: Associations with early adversity and depressive, anxiety and substance-use disorders. Translational Psychiatry, 6, e848. doi:10.1038/tp.2016.112 Google Scholar
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. doi:10.1371/journal.pone.0030148 Google Scholar
Tyrka, A. R., Ridout, K. K., & Parade, S. H. (2016). Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults. Development and Psychopathology, 28, 1319–1331. doi:10.1017/S0954579416000870 CrossRefGoogle ScholarPubMed
US Department of Health and Human Services, Administration for Children and Families, Administration on Children, Youth and Families, Children's Bureau. (2017). Child Maltreatment 2015. Retrieved from http://www.acf.hhs.gov/programs/cb/research-data-technology/statistics-research/child-maltreatment Google Scholar
van der Knaap, L. J., Riese, H., Hudziak, J. J., Verbiest, M. M., Verhulst, F. C., Oldehinkel, A. J., … van Oort, F. V. (2014). Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study. Translational Psychiatry, 4, e381. doi:10.1038/tp.2014.22 Google Scholar
van der Knaap, L. J., van Oort, F. V., Verhulst, F. C., Oldehinkel, A. J., & Riese, H. (2015). Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study. Journal of Affective Disorders, 180, 97–103. doi:10.1016/j.jad.2015.03.056 CrossRefGoogle ScholarPubMed
Vinkers, C. H., Kalafateli, A. L., Rutten, B. P., Kas, M. J., Kaminsky, Z., Turner, J. D., & Boks, M. P. (2015). Traumatic stress and human DNA methylation: A critical review. Epigenomics, 7, 593–608. doi:10.2217/epi.15.11 Google Scholar
Vukojevic, V., Kolassa, I. T., Fastenrath, M., Gschwind, L., Spalek, K., Milnik, A., … de Quervaine, D. J. (2014). Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. Journal of Neuroscience, 34, 10274–10284. doi:10.1523/jneurosci.1526-14.2014 CrossRefGoogle ScholarPubMed
Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., … Meaney, M. J. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–854. doi:10.1038/nn1276 Google Scholar
Weder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., … O'Loughlin, K. (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
Witzmann, S. R., Turner, J. D., Meriaux, S. B., Meijer, O. C., & Muller, C. P. (2012). Epigenetic regulation of the glucocorticoid receptor promoter 17 in adult rats. Epigenetics, 7, 1290–1301. doi:10.4161/epi.22363 CrossRefGoogle ScholarPubMed
Wong, C. C. Y., Caspi, A., Williams, B., Craig, I. W., Houts, R., Ambler, A., … Mill, J. (2010). A longitudinal study of epigenetic variation in twins. Epigenetics, 5, 516–526. doi:10.4161/epi.5.6.12226 Google Scholar
Yehuda, R., Daskalakis, N. P., Desarnaud, F., Makotkine, I., Lehrner, A. L., Koch, E., … Bierer, L. M. (2013). Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Frontiers in Psychiatry, 4, 118.Google Scholar
Yehuda, R., Flory, J. D., Bierer, L. M., Henn-Haase, C., Lehrner, A., Desarnaud, F., … Meaney, M. J. (2015). Lower methylation of glucocorticoid receptor gene promoter 1 F in peripheral blood of veterans with posttraumatic stress disorder. Biological Psychiatry, 77, 356–364. doi:10.1016/j.biopsych.2014.02.006 Google Scholar