Translational Behavioral Medicine

, Volume 6, Issue 1, pp 55–62 | Cite as

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

  • Moshe Szyf
  • Yi-Yang Tang
  • Karl G. Hill
  • Rashelle Musci


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.


DNA methylation Epigenetics Early life stress Translational science Interventions Gene environment Transgenerational Prevention science 



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

Compliance with ethical standards

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

Conflict of interest

The authors declare that they have no competing interests.


  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 7.
    Waddington CH. Canalization of development and genetic assimilation of acquired characters. Nature. 1959; 183(4676): 1654-5.CrossRefPubMedGoogle Scholar
  8. 8.
    Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7(8): 847-54.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jenuwein T. Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 2001; 11(6): 266-73.CrossRefPubMedGoogle Scholar
  12. 12.
    Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000; 403(6765): 41-5.CrossRefPubMedGoogle Scholar
  13. 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. 14.
    Razin A, Szyf M. DNA methylation patterns. Formation and function. Biochim Biophys Acta. 1984; 782(4): 331-42.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Goyal NK, Teeters A, Ammerman RT. Home visiting and outcomes of preterm infants: a systematic review. Pediatrics. 2013; 132(3): 502-16.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 22.
    Power C, Hertzman C. Social and biological pathways linking early life and adult disease. Br Med Bull. 1997; 53(1): 210-21.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Szyf M. The early-life social environment and DNA methylation. Clin Genet. 2012; 81(4): 341-9.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 27.
    Coe CL, Lubach GR. Prenatal influences on neuroimmune set points in infancy. Ann N Y Acad Sci. 2000; 917: 468-77.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Bhattacharya SK, Ramchandani S, Cervoni N, et al. A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999; 397: 579-583.CrossRefPubMedGoogle Scholar
  30. 30.
    Gavin DP, Chase KA, Sharma RP. Active DNA demethylation in post-mitotic neurons: a reason for optimism. Neuropharmacology. 2013; 75: 233-245.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 33.
    Szyf M. Prospects for the development of epigenetic drugs for CNS conditions. Nature Rev. 2015; 14: 461-474.Google Scholar
  34. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Masten AS, Burt KB, Coatsworth JD. Competence and psychopathology, vol. 3. Hoboken: Wiley; 2006: 696-738.Google Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.Google Scholar
  40. 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.Google Scholar

Copyright information

© Society of Behavioral Medicine 2016

Authors and Affiliations

  1. 1.Department of Pharmacology and TherapeuticsMcGill University Medical SchoolMontrealCanada
  2. 2.Texas Tech UniversityLubbockUSA
  3. 3.University of WashingtonSeattleUSA
  4. 4.Johns Hopkins UniversityBaltimoreUSA

Personalised recommendations