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Variation in DNA methylation of the oxytocin receptor gene predicts children's resilience to prenatal stress

Published online by Cambridge University Press:  22 November 2017

Izabela Milaniak ,
Charlotte A. M. Cecil ,
Edward D. Barker ,
Caroline L. Relton ,
Tom R. Gaunt ,
Wendy McArdle  and
Sara R. Jaffee
Izabela Milaniak
Affiliation:
University of Pennsylvania
Charlotte A. M. Cecil
Affiliation:
King's College London
Edward D. Barker
Affiliation:
King's College London
Caroline L. Relton
Affiliation:
University of Bristol
Tom R. Gaunt
Affiliation:
University of Bristol
Wendy McArdle
Affiliation:
University of Bristol
Sara R. Jaffee*
Affiliation:
University of Pennsylvania
*
Address correspondence and reprint requests to: Sara Jaffee, Department of Psychology, University of Pennsylvania, 425 South University Avenue, Philadelphia, PA 19104; E-mail: [email protected].
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Abstract

Emerging research in epigenetics has shown that there is variability in how environmental exposures “get under the skin” through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously associated with impairments in social–cognitive processes that may underlie a wide range of childhood psychopathology. Participants were 91 youth exposed to pre- and postnatal adversity with established conduct problem trajectories drawn from the Avon Longitudinal Study of Parents and Children. Consistent with our hypothesis, OXTR DNA methylation was predictive of resilience in the conduct problems domain in middle childhood. DNA methylation profiles did not predict resilience in domains of emotional, hyperactivity, and global symptomatology, suggesting a potential role for OXTR in the development of conduct problems in particular. However, individuals who were resilient to conduct problems were also broadly resilient across multiple domains. Therefore, future research should elucidate the biological pathways between OXTR DNA methylation and gene expression and its relation to impairments in social behavior.

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. 1663 - 1674
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole Avon Longitudinal Study of Parents and Children (ALSPAC) team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. With regard to the ALSPAC DNA methylation, we thank all involved, particularly the laboratory scientists and bioinformaticians who contributed considerable time and expertise to the data in this paper. The UK Medical Research Council and the Wellcome Trust (Grant 102215/2/13/2) and the University of Bristol provide core support for the ALSPAC. This publication is the work of the authors, who will serve as guarantors for the contents of this paper. This research was specifically supported by National Institute of Child and Human Development Grant R01HD068437 (to E.D.B.). ARIES was funded by the BBSRC (Grants BBI025751/1 and BB/I025263/1). Funding was provided by the Medical Research Council Integrative Epidemiology Unit at the University of Bristol Grants MC_UU_12013/2 and MC_UU_12013/8 (to C.L.R. and T.R.G). Finally, support was provided by the Economic and Social Research Council Grant ES/N001273/1 (to C.A.M.C.).

References

Bakulski, K. M., Halladay, A., Hu, V. W., Mill, J., & Fallin, M. D. (2016). Epigenetic research in neuropsychiatric disorders: The “Tissue Issue.” Current Behavioral Neuroscience Reports, 3, 264–274. doi:10.1007/s40473-016-0083-4 CrossRefGoogle ScholarPubMed
Barker, E. D., Jaffee, S. R., Uher, R., & Maughan, B. (2011). The contribution of prenatal and postnatal maternal anxiety and depression to child maladjustment. Depression and Anxiety, 28, 696–702. doi:10.1002/da.20856 CrossRefGoogle ScholarPubMed
Barker, E. D., & Maughan, B. (2009). Differentiating early-onset persistent versus childhood-limited conduct problem youth. American Journal of Psychiatry, 166, 900–908. doi:10.1176/appi.ajp.2009.08121770 Google Scholar
Barker, E. D., Oliver, B. R., & Maughan, B. (2010). Co-occurring problems of early onset persistent, childhood limited, and adolescent onset conduct problem youth. Journal of Child Psychology and Psychiatry, 51, 1217–1226.CrossRefGoogle ScholarPubMed
Bergman, K., Sarkar, P., Glover, V., & O'Connor, T. G. (2008). Quality of child–parent attachment moderates the impact of antenatal stress on child fearfulness. Journal of Child Psychology and Psychiatry, 49, 1089–1098. doi:10.1111/j.1469-7610.2008.01987.x CrossRefGoogle ScholarPubMed
Bergman, K., Sarkar, P., Glover, V., & O'Connor, T. G. (2010). Maternal prenatal cortisol and infant cognitive development: Moderation by infant–mother attachment. Biological Psychiatry, 67, 1026–1032. doi:10.1016/j.biopsych.2010.01.002 Google Scholar
Bick, J., Naumova, O., Hunter, S., Barbot, B., Lee, M., Luthar, S. S., … Grigorenko, E. L. (2012). Childhood adversity and DNA methylation of genes involved in the hypothalamus–pituitary–adrenal axis and immune system: Whole-genome and candidate-gene associations. Development and Psychopathology, 24, 1417–1425. doi:10.1017/S0954579412000806.Google Scholar
Billack, B., Serio, R., Silva, I., & Kinsley, C. H. (2012). Epigenetic changes brought about by perinatal stressors: A brief review of the literature. Journal of Pharmacological and Toxicological Methods, 66, 221–231. doi:10.1016/j.vascn.2012.08.169 Google Scholar
Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., … Davey Smith, G. (2013). Cohort profile: The ‘children of the 90s’—The index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology, 42, 111–127. doi:10.1093/ije/dys064 Google Scholar
Braithwaite, E. C., Murphy, S. E., & Ramchandani, P. G. (2014). Prenatal risk factors for depression: A critical review of the evidence and potential mechanisms. Journal of Developmental Origins of Health and Disease, 5, 339–350. doi:10.1017/S2040174414000324 Google Scholar
Byun, H. M., Siegmund, K. D., Pan, F., Weisenberger, D. J., Kanel, G., Laird, P. W., & Yang, A. S. (2009). Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Human Molecular Genetics, 18, 4808–4817. doi:10.1093/hmg/ddp445 Google Scholar
Cecil, C. A., Lysenko, L. J., Jaffee, S. R., Pingault, J. B., Smith, R. G., Relton, C. L., … Barker, E. D. (2014). Environmental risk, oxytocin receptor gene (OXTR) methylation and youth callous-unemotional traits: A 13-year longitudinal study. Molecular Psychiatry, 19, 1071–1077. doi:10.1038/mp.2014.95 CrossRefGoogle ScholarPubMed
Chen, Y., Lemire, M., Choufani, S., Butcher, D. T., Grafodatskaya, D., Zanke, B. W., … Weksberg, R. (2013). Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics, 8, 203–209. doi:10.4161/epi.23470 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 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics, 8, 1321–1329. doi:10.4161/epi.26634 Google Scholar
Dadds, M. R., Moul, C., Cauchi, A., Dobson-Stone, C., Hawes, D. J., Brennan, J., & Ebstein, R. E. (2014). Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy. Development and Psychopathology, 26, 33–40. doi:10.1017/S0954579413000497 Google Scholar
Davies, M. N., Volta, M., Pidsley, R., Lunnon, K., Dixit, A., Lovestone, S., … Mill, J. (2012). Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biology, 13, R43. doi:10.1186/gb-2012-13-6-r43 Google Scholar
Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V. K., Attwood, J., Burger, M., … Beck, S. (2006). DNA methylation profiling of human chromosomes 6, 20 and 22. Nature Genetics, 38, 1378–1385. doi:10.1038/ng1909 CrossRefGoogle Scholar
Fraser, A., Macdonald-Wallis, C., Tilling, K., Boyd, A., Golding, J., Smith, G. D., … Lawlor, D. A. (2013). Cohort profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. International Journal of Epidemiology, 42, 97–110. doi:10.1093/ije/dys066 CrossRefGoogle ScholarPubMed
Gaunt, T. R., Shihab, H. A., Hemani, G., Min, J. L., Woodward, G., Lyttleton, O., … Relton, C. L. (2016). Systematic identification of genetic influences on methylation across the human life course. Genome Biology, 17, 61. doi:10.1186/s13059-016-0926-z 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. doi:10.1056/NEJMra0708473 Google Scholar
Goodman, R. (1997). The Strengths and Difficulties Questionnaire: A research note. Journal of Child Psychology and Psychiatry, 38, 581–586. doi:10.1111/j.1469-7610.1997.tb01545.x Google Scholar
Goodman, R. (2001). Psychometric properties of the Strengths and Difficulties Questionnaire. Journal of the American Academy of Child & Adolescent Psychiatry, 40, 1337–1345. doi:10.1097/00004583-200111000-00015 CrossRefGoogle ScholarPubMed
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., … Pericak-Vance, M. A. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7, 62. doi:10.1186/1741-7015-7-62 CrossRefGoogle ScholarPubMed
Heinrichs, M., von Dawans, B., & Domes, G. (2009). Oxytocin, vasopressin, and human social behavior. Frontiers in Neuroendocrinology, 30, 548–557. doi:10.1016/j.yfrne.2009.05.005 Google Scholar
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
Houseman, E. A., Accomando, W. P., Koestler, D. C., Christensen, B. C., Marsit, C. J., Nelson, H. H., … Kelsey, K. T. (2012). DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics, 13, 86. doi:10.1186/1471-2105-13-86 CrossRefGoogle ScholarPubMed
Jack, A., Connelly, J. J., & Morris, J. P. (2012). DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Frontiers in Human Neuroscience, 6, 1–7. doi:10.3389/fnhum.2012.00280 CrossRefGoogle ScholarPubMed
Jaffee, S. R., Caspi, A., Moffitt, T. E., Polo-Tomás, M., & Taylor, A. (2007). Individual, family, and neighborhood factors distinguish resilient from non-resilient maltreated children: A cumulative stressors model. Child Abuse and Neglect, 31, 231–253. doi:10.1016/j.chiabu.2006.03.011 Google Scholar
Jaffee, S. R., & Gallop, R. (2007). Social, emotional, and academic competence among children who have had contact with Child Protective Services: Prevalence and stability estimates. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 757–765. doi:10.1097/chi.0b013e318040b247 Google Scholar
Johnson, W. E., Li, C., & Rabinovic, A. (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics, 8, 118–127. doi:10.1093/biostatistics/kxj037 CrossRefGoogle ScholarPubMed
Jones, M. J., Fejes, A. P., & Kobor, M. S. (2013). DNA methylation, genotype and gene expression: Who is driving and who is along for the ride? Genome Biology, 14, 126. doi:10.1186/gb-2013-14-7-126 Google Scholar
Jones, P. A. (2012). Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nature Reviews Genetics, 13, 484–492. doi:10.1038/nrg3230 Google Scholar
Kim-Cohen, J., Moffitt, T. E., Caspi, A., & Taylor, A. (2004). Genetic and environmental processes in young children's resilience and vulnerability to socioeconomic deprivation. Child Development, 75, 651–668. doi:10.1111/j.1467-8624.2004.00699.x Google Scholar
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., … Binder, E. B. (2013). Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions. Nature Neuroscience, 16, 33–41. doi:10.1038/nn.3275 Google Scholar
Kumsta, R., Hummel, E., Chen, F. S., & Heinrichs, M. (2013). Epigenetic regulation of the oxytocin receptor gene: Implications for behavioral neuroscience. Frontiers in Neuroscience, 7, 1–6. doi:10.3389/fnins.2013.00083 CrossRefGoogle ScholarPubMed
Kusui, C., Kimura, T., Ogita, K., Nakamura, H., Matsumura, Y., Koyama, M., … Murata, Y. (2001). DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochemical and Biophysical Research Communications, 289, 681–686. doi:10.1006/bbrc.2001.6024 Google Scholar
Lam, L. L., Emberly, E., Fraser, H. B., Neumann, S. M., Chen, E., Miller, G. E., & Kobor, M. S. (2012). Factors underlying variable DNA methylation in a human community cohort. Proceedings of the National Academy of Sciences, 109, 17253–17260. doi:10.1073/pnas.1121249109 Google Scholar
Laucht, M., Esser, G., Baving, L., Gerhold, M., Hoesch, I., Ihle, W., … Schmidt, M. H. (2000). Behavioral sequelae of perinatal insults and early family adversity at 8 years of age. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 1229–1237. doi:10.1097/00004583-200010000-00009 Google Scholar
Luthar, S. S., Cicchetti, D., & Becker, B. (2000). The construct of resilience: A critical evaluation and guidelines for future work. Child Development, 71, 543–562.Google Scholar
Luthar, S. S., Crossman, E. J., & Small, P. J. (2015). Resilience and adversity. In Lerner, R. M. & Lamb, M. E. (Eds.), Handbook of child psychology and developmental science (7th ed., Vol. 3, pp. 247–286). Hoboken, NJ: Wiley.Google Scholar
Mamrut, S., Harony, H., Sood, R., Shahar-Gold, H., Gainer, H., Shi, Y. J., … Wagner, S. (2013). DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor. PLOS ONE, 8, e56869. doi:10.1371/journal.pone.0056869 Google Scholar
Martinez-Torteya, C., Anne Bogat, G., Von Eye, A., & Levendosky, A. A. (2009). Resilience among children exposed to domestic violence: The role of risk and protective factors. Child Development, 80, 562–577. doi:10.1111/j.1467-8624.2009.01279.x Google Scholar
Masliah, E., Dumaop, W., Galasko, D., & Desplats, P. (2013). Distinctive patterns of DNA methylation associated with Parkinson disease. Epigenetics, 8, 1030–1038. doi:10.4161/epi.25865 CrossRefGoogle ScholarPubMed
Masten, A. (2013). Risk and resilience in development. In Zelazo, P. D. (Ed.), The Oxford handbook of developmental psychology: Vol. 2. Self and other (p. 579). Oxford: Oxford University Press. doi:10.1093/oxfordhb/9780199958474.013.0023 Google Scholar
McGowan, P. O., & Roth, T. L. (2015). Epigenetic pathways through which experiences become linked with biology. Development and Psychopathology, 27, 637–648. doi:10.1017/S0954579415000206 CrossRefGoogle ScholarPubMed
Moran, P., Ford, T., Butler, G., & Goodman, R. (2008). Callous and unemotional traits in children and adolescents living in Great Britain. British Journal of Psychiatry, 192, 65–66. doi:10.1192/bjp.bp.106.034876 CrossRefGoogle ScholarPubMed
Mulligan, C., D'Errico, N., Stees, J., & Hughes, D. (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
Oberlander, T. F., Papsdorf, M., Brain, U. M., Misri, S., Ross, C., & Grunau, R. E. (2010). Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age. Archives of Pediatrics and Adolescent Medicine, 164, 444–451. doi:10.1001/archpediatrics.2010.51 Google Scholar
O'Connor, T. G., Heron, J., Golding, J., Beveridge, M., & Glover, V. (2002). Maternal antenatal anxiety and children's behavioural/emotional problems at 4 years. British Journal of Psychiatry, 180, 502–508. doi:10.1192/bjp.180.6.502 Google Scholar
O'Donnell, K. J., Glover, V., Barker, E. D., & O'Connor, T. G. (2014). The persisting effect of maternal mood in pregnancy on childhood psychopathology. Development and Psychopathology, 26, 393–403. doi:10.1017/S0954579414000029 CrossRefGoogle ScholarPubMed
Oland, A. A., & Shaw, D. S. (2005). Pure versus co-occurring externalizing and internalizing symptoms in children: The potential role of socio-developmental milestones. Clinical Child and Family Psychology Review, 8, 247–270. doi:10.1007/s10567-005-8808-z Google Scholar
Patterson, G. R., DeBaryshe, B. D., & Ramsey, E. (1989). A developmental perspective on antisocial behavior. American Psychologist, 44, 329–335.CrossRefGoogle ScholarPubMed
Pawlby, S., Hay, D. F., Sharp, D., Waters, C. S., & O'Keane, V. (2009). Antenatal depression predicts depression in adolescent offspring: Prospective longitudinal community-based study. Journal of Affective Disorders, 113, 236–243. doi:10.1016/j.jad.2008.05.018 Google Scholar
Perroud, N., Rutembesa, E., Paoloni-Giacobino, A., Mutabaruka, J., Mutesa, L., Stenz, L., … Karege, F. (2014). The Tutsi genocide and transgenerational transmission of maternal stress: Epigenetics and biology of the HPA axis. World Journal of Biological Psychiatry, 15, 334–345. doi:10.3109/15622975.2013.866693 CrossRefGoogle ScholarPubMed
Pluess, M., Velders, F. P., Belsky, J., van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., Jaddoe, V. W. V., … Tiemeier, H. (2011). Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality. Biological Psychiatry, 69, 520–525. doi:10.1016/j.biopsych.2010.10.006 Google Scholar
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., & Elbert, T. (2011). Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry, 1, e21. doi:10.1038/tp.2011.21 Google Scholar
Reiner, I., van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., Bleich, S., Beutel, M., & Frieling, H. (2015). Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype. Journal of Psychiatric Research, 65, 9–15. doi:10.1016/j.jpsychires.2015.03.012 Google Scholar
Relton, C. L., Gaunt, T., McArdle, W., Ho, K., Duggirala, A., Shihab, H., … Smith, G. D. (2015). Data resource profile: Accessible Resource for Integrated Epigenomic Studies (ARIES). International Journal of Epidemiology. Advance online publication. doi:10.1093/ije/dyv072 Google Scholar
Rice, F., Jones, I., & Thapar, A. (2007). The impact of gestational stress and prenatal growth on emotional problems in offspring: A review. Acta Psychiatrica Scandinavica, 115, 171–183. doi:10.1111/j.1600-0447.2006.00895.x Google Scholar
Robinson, M., Mattes, E., Oddy, W. H., Pennell, C. E., van Eekelen, A., McLean, N. J., … Newnham, J. P. (2011). Prenatal stress and risk of behavioral morbidity from age 2 to 14 years: The influence of the number, type, and timing of stressful life events. Development and Psychopathology, 23, 507–520. doi:10.1017/S0954579411000241 Google Scholar
Ronald, A., Pennell, C. E., & Whitehouse, A. J. O. (2011). Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Developmental Psychology, 1, 223. doi:10.3389/fpsyg.2010.00223 Google Scholar
Rutter, M. (2006). Implications of resilience concepts for scientific understanding. Annals of the New York Academy of Sciences, 1094, 1–12. doi:10.1196/annals.1376.002 Google Scholar
Rutter, M. (2012). Resilience as a dynamic concept. Development and Psychopathology, 24, 335–344. doi:10.1017/S0954579412000028 Google Scholar
Skuse, D. H., Mandy, W. P. L., & Scourfield, J. (2005). Measuring autistic traits: Heritability, reliability and validity of the Social and Communication Disorders Checklist. British Journal of Psychiatry, 187, 568–572. doi:10.1192/bjp.187.6.568 Google Scholar
Unternaehrer, E., Meyer, A. H., Burkhardt, S. C. A., Dempster, E., Staehli, S., Theill, N., … Meinlschmidt, G. (2015). Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women. Stress, 18, 451–461. doi:10.3109/10253890.2015.1038992 CrossRefGoogle ScholarPubMed
Van den Bergh, B. R. H., & Marcoen, A. (2004). High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Development, 75, 1085–1097. doi:10.1111/j.1467-8624.2004.00727.x CrossRefGoogle ScholarPubMed
Van der Knaap, L. J., Riese, H., Hudziak, J. J., Verbiest, M. M. P. J., Verhulst, F. C., Oldehinkel, A. J., & van Oort, F. V. A. (2015). Adverse life events and allele-specific methylation of the serotonin transporter gene (SLC6A4) in adolescents: The TRAILS study. Psychosomatic Medicine, 77, 246–255. doi:10.1097/psy.0000000000000159 CrossRefGoogle ScholarPubMed
Velders, F. P., Dieleman, G., Cents, R. A., Bakermans-Kranenburg, M. J., Jaddoe, V. W., Hofman, A., … Tiemeier, H. (2012). Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior. Neuropsychopharmacology, 37, 2541–2549. doi:10.1038/npp.2012.118 Google Scholar
Walton, E., Hass, J., Liu, J., Roffman, J. L., Bernardoni, F., Roessner, V., … Ehrlich, S. (2016). Correspondence of DNA methylation between blood and brain tissue and its application to schizophrenia research. Schizophrenia Bulletin, 42, 406–414. doi:10.1093/schbul/sbv074 Google Scholar
Ziegler, C., Dannlowski, U., Bräuer, D., Stevens, S., Laeger, I., Wittmann, H., … Domschke, K. (2015). Oxytocin receptor gene methylation: Converging multilevel evidence for a role in social anxiety. Neuropsychopharmacology, 40, 1528–1538. doi:10.1038/npp.2015.2 CrossRefGoogle ScholarPubMed