Open Access Dissertation
Date of Award
Molecular Biology and Genetics
Posttraumatic stress disorder (PTSD) is an important medical and social condition. Although the vast majority of individuals are exposed to traumatic events within their lifetime, a minority subsequently develop diagnosable PTSD. What underlies differential risk and resiliency in the face of trauma is an ongoing research and clinical question with implications for prevention and treatment. Recent work has revealed a putative role of epigenetic variation and modification - most notably DNA methylation - in the etiology of PTSD. That DNA methylation is stable, yet modifiable in response to lived experiences, makes it a strong candidate to mechanistically explain the ontogeny of PTSD by putatively linking genetic and environment effects. Here, I provide proximate and evolutionary insights into this biological capacity through three distinct, but conceptually related research projects. In the first, I compare DNA methylation longitudinally in trauma-exposed individuals with and without PTSD to reveal a complex role of epigenetic variation and modification in PTSD development. In the second, I utilize phylogenetic methods to infer and characterize the evolutionary history of genetic loci necessary for the epigenetic regulation of PTSD, revealing that this capacity may have ancient origins. In the third, I test, and fail to provide evidence for, genetic associations between PTSD risk and single nucleotide polymorphisms (SNPs) annotated to genes involved in the regulation and activity of the hypothalamic-pituitary-adrenal (HPA) axis. Taken together, these data are suggestive of an evolutionarily-conserved capacity to regulate behavior, physiology, and psychology in response to extreme traumatic experiences. I argue that this capacity is epigenetically regulated and represents an example of adaptive developmental phenotypic plasticity. This model of PTSD etiology has implications for policy, clinical practice, public health, and research.
Sipahi, Levent, "Proximate And Evolutionary Insights Into The Epigenetics Of Posttraumatic Stress Disorder" (2014). Wayne State University Dissertations. 1026.