Ancient evolutionary origins of epigenetic regulation associated with posttraumatic stress disorder
Open accessAbstract
Epigenetic marks, including DNA methylation, are modifiable molecular factors that may underlie mental disorders, especially responses to trauma, including the development of and resilience to posttraumatic stress disorder (PTSD). Previous work has identified differential DNA methylation at CpG dinucleotide sites genomewide between trauma exposed individuals with and without PTSD, suggesting a role for epigenetic potential-the capacity to epigenetically regulate behavior and physiology in response to lived experiences. The human species is characterized by an increased period of adaptive plasticity during brain development. The evolutionary history of epigenetic potential in relation to adaptive plasticity is currently unknown. Using phylogenetic methods and functional annotation analyses, we trace the evolution of over 7000 CpG dinucleotides, including 203 associated with PTSD, during the descent of humans in during mammalian evolution and characterize the biological significance of this evolution. We demonstrate that few (7%) PTSD-associated CpG sites are unique to humans, while the vast majority of sites have deep evolutionary origins: 73 and 93% were unambiguously present in the last common ancestor of humans/orangutans and humans/chimpanzees, respectively. Genes proximal to evolved PTSD-associated CpG sites revealed significant enrichment for immune function during recent human evolution and regulation of gene expression during more ancient periods of human evolution. Additionally, 765 putative transcription factor binding motifs (TFBMs) were identified that overlap with PTSD-associated CpG sites. Elucidation of the evolutionary history of PTSD-associated CpG sites may provide insights into the function and origin of epigenetic potential in trauma responses, generally, and PTSD, specifically. The human capacity to respond to trauma with stable physiologic and behavioral changes may be due to epigenetic potentials that are shared among many mammalian species.
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In a first pilot study, Sipahi et al. (2014) found that the majority of PTSD-associated CpG sites are shared by all primates, while PTSD-associated CpG sites proximal to immune system-related genes may have disproportionately evolved during the more recent evolutionary history.
“In a first pilot study, Sipahi et al. (2014) have traced and characterized the evolution of genomic sites associated with the development of PTSD and found that the majority of PTSD-associated CpG sites are shared by all primates, while PTSD-associated CpG sites proximal to immune system-related genes may have disproportionately evolved during the more recent evolutionary history.”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Sipahi et al., 2014
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References 41 · Cited by 18
Research works printed but not linked: 2
- American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Publishing
- Horwitz A. V Wakefield J. C. (2012). All We Have to Fear: Psychiaty's Transformation of Natural Anxieties into Mental Disorders. New York, NY: Oxford University Press
- Authors
- Sipahi, L., Uddin, M., Hou, Z.-C., Aiello, A. E., Koenen, K. C., Galea, S., & Wildman, D. E.
- Affiliations
- Wayne State University (US)
- University of North Carolina at Chapel Hill (US)
- Columbia University (US)
- Corresponding author
- Wildman, Derek E.
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-05-13
- Volume
- 8
- Pages
- 284-284
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC4026723
- OpenAlex
- W2168413641
- Cited by
- 18
- References
- 41
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 3 · 2018: 4 · 2016: 1 · 2015: 2 · 2014: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- National Science Foundation (0827546)
- Wayne State University
- National Institutes of Health
- National Institute of Mental Health (RC1MH088283)
- National Institute on Drug Abuse (R01DA022720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, DNA methylation, CpG sites, evolutionary origin, human evolution, adaptive plasticity, brain development, immune function genes, transcription factor binding motifs, trauma response, phylogenetic analysis, chimpanzees, orangutans
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