Epigenetics is a rapidly growing field that has provided insight into the etiology of many physiological mechanisms. Research around post-traumatic stress disorder (PTSD) has evolved immensely since expanding to include an epigenetic lens. Researchers have studied which gene loci are associated with PTSD to understand how genes can become either over or under expressed when exposed to trauma. The three main epigenetic factors that assist with regulating the genome are: DNA methylation, histone modification (including methylation and acetylation), and noncoding RNA. Each factor utilizes a different mechanism to help with either the upregulation or downregulation of a specific gene.
Within PTSD research, the impacts of these genome modifications have been studied to understand how they regulate the common physiological symptoms associated with PTSD diagnoses. These symptomologies include decreased basal cortisol levels, decreased cardiovascular health, decreased immune function, and increased mortality. Many epigenetic studies have explored how changes in specific gene loci contribute to these physiological dysregulations. Some genes of interest include nuclear receptor subfamily 3 group C member 1 (NR3C1), FK506 binding protein 5 (FKBP5), and spindle and kinetochore-associated protein 2 (SKA2). Many studies have been conducted examining the DNA methylation activity of each gene in those with PTSD diagnoses and those without. However, research continues to produce mixed results. While some studies show an increase of DNA methylation for a specific gene in subjects with PTSD, other studies evidence a decrease of DNA methylation for the same gene.
Examining the reasons for conflicting evidence is valuable to further understand the epigenetic mechanisms that occur. After conducting a literature review, four confounding factors have been identified as contributors to such mixed results. The first factor is the difference in each study’s definition of trauma, as well as the diagnostic tools they use to identify subjects with PTSD. The second factor is the samples used to detect epigenetic changes. Most samples collected in epigenetic studies of PTSD include whole blood samples, salivary samples, and only rarely, brain tissue samples. These different sample types, when cross-compared, can contribute to discrepancies in DNA methylation data. Furthermore, whole blood samples are not only vulnerable to intrinsic factor variabilities, but external factor variabilities. The third factor is a difference in subject population across the literature. Many studies are focused on either combat-veterans (with all male subjects) or child cohorts. These differences in demographics make it difficult to compare groups, as research indicates several epigenetic factors such as DNA methylation activity are sex, ethnicity, and age dependent. Finally, the fourth confounding factor is age at onset of trauma. Many studies show that trauma exposure in childhood leads to more severe symptoms compared to trauma exposure in adulthood.
It is important to consider these factors and account for confounding variables when conducting future research. In doing so, more robust and accurate research can be produced. A more refined understanding of the epigenetic etiology of PTSD, as well as its epigenetic biomarkers, will likely yield greater insight into PTSD diagnoses, as well as best treatment practices.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48399 |
| Date | 14 March 2024 |
| Creators | Vildorf, Danielle |
| Contributors | Gerstenfeld, Louis C., Huddy, Jessica |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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