Evidence from quantitative and molecular genetic studies have repeatedly demonstrated the involvement of genes in post-traumatic stress disorder (PTSD), but also highlighted the importance of environmental factors in disease development and/or resilience. The emerging field of epigenetics is particularly attractive because of its ability to account for individual differences in response to trauma based on environmental exposures that alter gene function. As such, investigation of specific epigenetic markers may provide quantifiable measures of lifetime environmental stress or heritable predisposition to PTSD and can thus offer a biological framework for the interactive causes underlying PTSD. In this mini-review we will discuss the relevance of epigenetic research to PTSD and provide a summary of recent developments revealing epigenetic alterations in response to adversities, trauma and PTSD.
Epigenetics Explained in Brief
Coined by Waddington, the term “epigenetics” was originally used to describe how genes interact with the cellular environment to produce a phenotype (Waddington, 1942). Nowadays, the term is applied more narrowly referring to the reversible regulation of various genomic functions, occurring independently of DNA sequence, mediated principally through changes in DNA methylation and chromatin structure. In other words, epigenetics defines cellular modifications that can be heritable but appear largely unrelated to DNA sequence changes, and that can be modified by environmental stimuli (Holliday, 1994, Russo et al., 1996). Such modifications are stable and long lasting and can in some cases be transmitted inter-generationally (Meaney & Szyf, 2005). At present, epigenetic mechanisms typically comprise DNA methylation and histone modifications. DNA methylation is strongly linked to a number of genomic functions, including the regulation of gene expression, with many genes demonstrating an inverse correlation between the degree of methylation and the level of expression (Jaenisch & Bird, 2003). Genome-wide DNA methylation variation is a new way of looking at complex diseases such as PTSD because it responds to the environment and governs gene expression - thus potentially mediating a path from environmental effects to gene expression to disease.