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The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion

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Translational Behavioral Medicine

Abstract

The emerging field of behavioral epigenetics is producing a growing body of evidence that early life experience and social exposure can alter the way by which genes are marked with DNA methylation. We hypothesize that changes in DNA methylation as well as other epigenetic markers could generate stable phenotypes. Early life adversity appears to result in altered DNA methylation of genes in the brain and peripheral tissues, and these changes are associated with adverse phenotypic changes. Although the data are still sparse, early epigenetic studies have provided a proof of principle that experiences and the environment leave marks on genes, and thus suggest molecular and physical mechanisms for the epidemiological concept of gene-environment interaction. The main attraction of DNA methylation for type I (TI) translational prevention science is the fact that, different from genetic changes that are inherited from our ancestors, DNA methylation is potentially preventable and reversible and, therefore, there is a prospect of epigenetically targeted interventions. In addition, DNA methylation markers might provide an objective tool for assessing effects of early adverse experience on individual risks as well as providing objective measures of progress of an intervention. In spite of this great potential promise of the emerging field of social and translational epigenetics, many practical challenges remain that must be addressed before behavioral epigenetics could become translational epigenetics.

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References

  1. Cohen-Woods S, Craig IW, McGuffin P. The current state of play on the molecular genetics of depression. Psychol Med. 2013; 43(4): 673-87.

    Article  CAS  PubMed  Google Scholar 

  2. Schwab SG, Wildenauer DB. Genetics of psychiatric disorders in the GWAS era: an update on schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2013; 263(Suppl 2): 147-54.

    Article  Google Scholar 

  3. Stergiakouli E, Hamshere M, Holmans P, et al. Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am J Psychiatry. 2012; 169(2): 186-94.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Murakami F, Shimomura T, Kotani K, et al. Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese. J Hum Genet. 1999; 44(1): 15-7.

    Article  CAS  PubMed  Google Scholar 

  5. Binder EB, Salyakina D, Lichtner P, et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 2004; 36(12): 1319-25.

    Article  CAS  PubMed  Google Scholar 

  6. Eisenberger NI, Way BM, Taylor SE, et al. Understanding genetic risk for aggression: clues from the brain’s response to social exclusion. Biol Psychiatry. 2007; 61(9): 1100-8.

    Article  PubMed  Google Scholar 

  7. Waddington CH. Canalization of development and genetic assimilation of acquired characters. Nature. 1959; 183(4676): 1654-5.

    Article  CAS  PubMed  Google Scholar 

  8. Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7(8): 847-54.

    Article  CAS  PubMed  Google Scholar 

  9. Jin SG, Wu X, Li AX, et al. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 2011; 39(12): 5015-24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in purkinje neurons and the brain. Science. 2009; 324(5929): 929-30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jenuwein T. Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 2001; 11(6): 266-73.

    Article  CAS  PubMed  Google Scholar 

  12. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000; 403(6765): 41-5.

    Article  CAS  PubMed  Google Scholar 

  13. Szyf M, McGowan PO, Turecki J, et al. The social environment and the epigenome. In: Worthman CM, Plotsky PM, Schechter DS, Cummings CA, eds. Formative experiences the interaction of caregiving, culture, and developmental psychobiology. Cambridge: Cambridge University Press; 2013: 53-82. 3.

    Google Scholar 

  14. Razin A, Szyf M. DNA methylation patterns. Formation and function. Biochim Biophys Acta. 1984; 782(4): 331-42.

    Article  CAS  PubMed  Google Scholar 

  15. Comb M, Goodman HM. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res. 1990; 18(13): 3975-82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Inamdar NM, Ehrlich KC, Ehrlich M. CpG methylation inhibits binding of several sequence-specific DNA- binding proteins from pea, wheat, soybean and cauliflower. Plant Mol Biol. 1991; 17(1): 111-23.

    Article  CAS  PubMed  Google Scholar 

  17. Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997; 88(4): 471-81.

    Article  CAS  PubMed  Google Scholar 

  18. Weaver IC, Meaney MJ, Szyf M. Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci U S A. 2006; 103(9): 3480-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Francis D, Diorio J, Liu D, et al. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science. 1999; 286(5442): 1155-8.

    Article  CAS  PubMed  Google Scholar 

  20. Goyal NK, Teeters A, Ammerman RT. Home visiting and outcomes of preterm infants: a systematic review. Pediatrics. 2013; 132(3): 502-16.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kaminski JW, Valle LA, Filene JH, et al. A meta-analytic review of components associated with parent training program effectiveness. J Abnorm Child Psychol. 2008; 36(4): 567-89.

    Article  PubMed  Google Scholar 

  22. Power C, Hertzman C. Social and biological pathways linking early life and adult disease. Br Med Bull. 1997; 53(1): 210-21.

    Article  CAS  PubMed  Google Scholar 

  23. Power C, Jefferis BJ, Manor O, et al. The influence of birth weight and socioeconomic position on cognitive development: does the early home and learning environment modify their effects? J Pediatr. 2006; 148(1): 54-61.

    Article  PubMed  Google Scholar 

  24. McGowan PO, Suderman M, Sasaki A, et al. Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One. 2011; 6(2): e14739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Szyf M. The early-life social environment and DNA methylation. Clin Genet. 2012; 81(4): 341-9.

    Article  CAS  PubMed  Google Scholar 

  26. Provencal N, Suderman MJ, Guillemin C, et al. The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells. J Neurosci: Off J Soc Neurosci. 2012; 32(44): 15626-15642.

    Article  CAS  Google Scholar 

  27. Coe CL, Lubach GR. Prenatal influences on neuroimmune set points in infancy. Ann N Y Acad Sci. 2000; 917: 468-77.

    Article  CAS  PubMed  Google Scholar 

  28. Ramchandani S, Bhattacharya SK, Cervoni N, et al. DNA methylation is a reversible biological signal. Proc Natl Acad Sci U S A. 1999; 96: 6107-6112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bhattacharya SK, Ramchandani S, Cervoni N, et al. A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999; 397: 579-583.

    Article  CAS  PubMed  Google Scholar 

  30. Gavin DP, Chase KA, Sharma RP. Active DNA demethylation in post-mitotic neurons: a reason for optimism. Neuropharmacology. 2013; 75: 233-245.

    Article  CAS  PubMed  Google Scholar 

  31. Rai K, Huggins IJ, James SR, et al. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell. 2008; 135: 1201-1212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Massart R, Barnea R, Dikshtein Y, et al. Role of DNA methylation in the nucleus accumbens in incubation of cocaine craving. J Neurosci. 2015; 35: 8042-8058.

    Article  CAS  PubMed  Google Scholar 

  33. Szyf M. Prospects for the development of epigenetic drugs for CNS conditions. Nature Rev. 2015; 14: 461-474.

    CAS  Google Scholar 

  34. McGowan PO, Sasaki A, Huang TC, et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One. 2008; 3(5): e2085.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Suderman M, McGowan PO, Sasaki A, et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc Natl Acad Sci U S A. 2012; 109(Suppl 2): 17266-17272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Masten AS, Burt KB, Coatsworth JD. Competence and psychopathology, vol. 3. Hoboken: Wiley; 2006: 696-738.

    Google Scholar 

  37. Eckenrode J, Campa M, Luckey DW, et al. Long-term effects of prenatal and infancy nurse home visitation on the life course of youths: 19-year follow-up of a randomized trial. Arch Pediatr Adolesc Med. 2010; 164(1): 9-15.

    Article  PubMed  Google Scholar 

  38. Zielinski DS, Eckenrode J, Olds DL. Nurse home visitation and the prevention of child maltreatment: impact on the timing of official reports. Dev Psychopathol. 2009; 21(2): 441-53.

    Article  PubMed  Google Scholar 

  39. Hawkins JD, Kosterman R, Catalano RF, Hill KG, Abbott RD. Effects of social development intervention in childhood 15 years later. Arch Pediatr Adolesc Med. 2008; 162(12): 1133-1141.

  40. Hill KG, Bailey JA, Hawkins JD, Catalano RF, Kosterman R, Oesterle S, Abbott RD. The onset of STI diagnosis through age 30: results from the Seattle Social Development Project intervention. Prev Sci. 2014; 15(Suppl 1): S19-S32.

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Acknowledgments

The work on this transdisciplinary manuscript resulted from a National Institute of Nursing Research-funded R13 conference “Advancing Transdisciplinary Translation for Prevention of High-Risk Behaviors: Critical Thinking to Overcome Individual and Institutional Barriers” (R13NR013623-01-02). Additional support for this paper was provided in part by a grant from the National Institute on Drug Abuse (R01DA024411 01-06). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINR or NIDA. MS is supported by CIHR-MOP-42411

Author information

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, McGill University Medical School, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada, H3G1Y6

    Moshe Szyf Ph.D.

  2. Texas Tech University, Lubbock, TX, USA

    Yi-Yang Tang Ph.D.

  3. University of Washington, Seattle, WA, USA

    Karl G. Hill Ph.D.

  4. Johns Hopkins University, Baltimore, MD, USA

    Rashelle Musci Ph.D.

Authors
  1. Moshe Szyf Ph.D.
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  2. Yi-Yang Tang Ph.D.
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  3. Karl G. Hill Ph.D.
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  4. Rashelle Musci Ph.D.
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Corresponding author

Correspondence to Moshe Szyf Ph.D..

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The paper is a review article and discusses published studies. No primary studies with ethics requirements are discussed.

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The authors declare that they have no competing interests.

Additional information

Implications

Researchers: provides a review and insight into the science of epigenetics and its implications in neuroscience.

Practitioners: introduce the practitioners to implications of the science of epigenetics on understanding, preventing, and treating behavioral disorders

Policy makers: the implications that epigenetics has on social policy

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Szyf, M., Tang, YY., Hill, K.G. et al. The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion. Behav. Med. Pract. Policy Res. 6, 55–62 (2016). https://doi.org/10.1007/s13142-016-0387-7

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  • DOI: https://doi.org/10.1007/s13142-016-0387-7

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