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

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.

Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells

“…The ability of the PGCLC cell culture model to erase experimentally introduced epimutations will provide unique future opportunities to examine erasure, and possible retention, of various types of epimutations at specific gDNA locations during germline differentiation. It remains to be determined whether this PGCLC model can also be used to examine erasure of epimutations introduced outside ICRs and/or within repetitive elements, and the resolution power of this approach should be improved at the nucleotide base level because experience-induced changes in gametic gDNA methylation were reported to be specific to CpG sites, thus critically affecting gDNA binding to transcription factors (32,33). It is also an interesting question as to whether or not apparently physiological epigenetic changes resulting from specific and regulated mechanisms (vs. stochastic, nonphysiological epimutations) are erased in the PGCLCs.…”

The effects of racism on the human body

“…One of the most disturbing set of discoveries emanating from research on epigenesis is that the stresses realised by an individual can affect not only the way the genes of a person work, but that some of these stress-related modifications are heritable (Szyf, Tang, Hill & Musci, 2016;Vandegehuchte & Janssen, 2014). When genes that control the expression of brain proteins or that modify the function of the immune system are affected by environmental (including psychosocial) stressors, the effects can be extremely serious.…”

“…New evidence indicates, however, that DNA methylation may not result in indelible epigenetic marks and that different signals arriving at intervals over a lifetime act on the genome and epigenome of the time to affect the next phase of life (Patchev, Rodrigues, Sousa, Spengler & Almeida, 2014). Amongst the many things we don't yet know is how consistent exposure to positive, supportive environments produce a methylation pattern that places children on a positive developmental trajectory, and more resilient to subsequent adversities (Szyf et al, 2016). We are also ignorant of the mechanisms whereby DNA methylation patterns defined by early life experience are altered with childhood, adolescence, and adult experience, and how these changes relate to environmental exposures (ibid.).…”

Developmental lead and/or prenatal stress exposures followed by different types of behavioral experience result in the divergence of brain epigenetic profiles in a sex, brain region, and time-dependent manner: Implications for neurotoxicology

“…It seems more likely that an iterative reductionist-holistic approach will prove more fruitful, in searching for patterns of epigenetic changes that link to functional brain networks [72]. Such an understanding is critical because it could ideally be utilized to devise specific behavioral interventions to reverse earlier adverse environmental impacts [81]. …”