Stress Across Generations: DNA Methylation as a Potential Mechanism Underlying Intergenerational Effects of Stress in Both Post-traumatic Stress Disorder and Pre-clinical Predator Stress Rodent Models
Open accessAbstract
Although most humans will experience some type of traumatic event in their lifetime only a small set of individuals will go on to develop post-traumatic stress disorder (PTSD). Differences in sex, age, trauma type, and comorbidity, along with many other elements, contribute to the heterogenous manifestation of this disorder. Nonetheless, aberrant hypothalamus-pituitary-adrenal (HPA) axis activity, especially in terms of cortisol and glucocorticoid receptor (GR) alterations, has been postulated as a tenable factor in the etiology and pathophysiology of PTSD. Moreover, emerging data suggests that the harmful effects of traumatic stress to the HPA axis in PTSD can also propagate into future generations, making offspring more prone to psychopathologies. Predator stress models provide an ethical and ethologically relevant way to investigate tentative mechanisms that are thought to underlie this phenomenon. In this review article, we discuss findings from human and laboratory predator stress studies that suggest changes to DNA methylation germane to GRs may underlie the generational effects of trauma transmission. Understanding mechanisms that promote stress-induced psychopathology will represent a major advance in the field and may lead to novel treatments for such devastating, and often treatment-resistant trauma and stress-disorders.
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Many studies of predator stress have found that methylation of Nr3c1 genes and Fkbp5 appear to play a role in the transmission of these effects to future generations.
“Many studies of predator stress have found that methylation of Nr3c1 genes and Fkbp5 appear to play a role in the transmission of these effects to future generations [74].”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [74]
The Conclusion (page not available) says that predator exposure during pregnancy alters GR/Nr3c1 and FKBP5 methylation in offspring, consistent with the claim’s proposed link. But Table 2 identifies only one predator-stress offspring study involving those genes, and the Conclusion says methylation’s role in transmitting stress remains unknown. The claim overstates the evidence as a finding of many studies. (LLM, conf=0.88)
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- Authors
- Bhattacharya, S., Fontaine, A., MacCallum, P. E., Drover, J., & Blundell, J.
- Affiliations
- Memorial University of Newfoundland (CA)
- Corresponding author
- Blundell, Jacqueline
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-05-28
- Volume
- 13
- Pages
- 113-113
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC6547031
- OpenAlex
- W2947680512
- Semantic Scholar
- 518b5083c6bf524cd6c75999a88e29a5687f7492
- Cited by
- 40
- References
- 150
- Citations by year
- 2025: 11 · 2024: 4 · 2023: 10 · 2022: 7 · 2021: 4 · 2020: 4
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- post-traumatic stress disorder, DNA methylation, glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, predator stress, rodent models, cortisol, epigenetics
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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