Deconvoluting the functional role of DNA methylation in trauma; Implications for epigenetic therapy and prospects of targeted “epigenetic therapy”

Traumatic experience has long-term consequences, which manifest as posttraumatic stress disorder (PTSD). However, not all those exposed to the same trauma would be susceptible to developing PTSD; a majority of those exposed remain resilient. DNA methylation is a covalent modification of DNA that is associated with cell type differentiation; cell type–specific patterns form during embryonal development. Environmental and behavioral exposures are associated with alterations in DNA methylation patterns. Using a rat model of PTSD, we examined whether traumatic exposures alter DNA methylation in the brain, whether there is a difference in DNA methylation between “resilient” and “susceptible” individuals, and whether PTSD could be reversed by altering the expression of genes involved in DNA methylation alterations in susceptible animals. We present a new method for determining the causal role of specific DNA methylation alterations and for site-specific inhibition of DNA methylation.