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
- PMID: 31191267
- PMCID: PMC6547031
- DOI: 10.3389/fnbeh.2019.00113
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
Abstract
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.
Keywords: DNA methylation; FKBP5; PTSD; glucocorticoid receptors; intergenerational; predator stress.
Similar articles
-
[Posttraumatic stress disorder (PTSD) as a consequence of the interaction between an individual genetic susceptibility, a traumatogenic event and a social context].Encephale. 2012 Oct;38(5):373-80. doi: 10.1016/j.encep.2011.12.003. Epub 2012 Jan 24. Encephale. 2012. PMID: 23062450 Review. French.
-
Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.Biol Sex Differ. 2018 Jul 5;9(1):31. doi: 10.1186/s13293-018-0191-9. Biol Sex Differ. 2018. PMID: 29976248 Free PMC article.
-
Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder.Biol Psychiatry. 2015 Feb 15;77(4):356-64. doi: 10.1016/j.biopsych.2014.02.006. Epub 2014 Feb 17. Biol Psychiatry. 2015. PMID: 24661442
-
Allele-specific DNA methylation level of FKBP5 is associated with post-traumatic stress disorder.Psychoneuroendocrinology. 2019 May;103:1-7. doi: 10.1016/j.psyneuen.2018.12.226. Epub 2018 Dec 19. Psychoneuroendocrinology. 2019. PMID: 30605803
-
Early Life Stress as a Predictor of Co-Occurring Alcohol Use Disorder and Post-Traumatic Stress Disorder.Alcohol Res. 2018;39(2):147-159. Alcohol Res. 2018. PMID: 31198654 Free PMC article. Review.
Cited by
-
A narrative review of the epigenetics of post-traumatic stress disorder and post-traumatic stress disorder treatment.Front Psychiatry. 2022 Nov 7;13:857087. doi: 10.3389/fpsyt.2022.857087. eCollection 2022. Front Psychiatry. 2022. PMID: 36419982 Free PMC article. Review.
-
Prenatal earthquake stress exposure in different gestational trimesters is associated with methylation changes in the glucocorticoid receptor gene (NR3C1) and long-term working memory in adulthood.Transl Psychiatry. 2022 Apr 29;12(1):176. doi: 10.1038/s41398-022-01945-7. Transl Psychiatry. 2022. PMID: 35487912 Free PMC article.
-
Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans.Front Psychiatry. 2023 May 25;14:1145375. doi: 10.3389/fpsyt.2023.1145375. eCollection 2023. Front Psychiatry. 2023. PMID: 37398583 Free PMC article.
-
Understanding stress: Insights from rodent models.Curr Res Neurobiol. 2021 May 23;2:100013. doi: 10.1016/j.crneur.2021.100013. eCollection 2021. Curr Res Neurobiol. 2021. PMID: 36246514 Free PMC article. Review.
-
Trauma context exerts intergenerational effects on child mental health via DNA methylation.Epigenetics. 2024 Dec;19(1):2333654. doi: 10.1080/15592294.2024.2333654. Epub 2024 Apr 5. Epigenetics. 2024. PMID: 38577817 Free PMC article.
References
-
- Adamec R. E., Burton P., Shallow T., Budgell J. (1999). NMDA receptors mediate lasting increases in anxiety-like behavior produced by the stress of predator exposure—implications for anxiety associated with posttraumatic stress disorder. Physiol. Behav. 65, 723–737. 10.1016/s0031-9384(98)00226-1 - DOI - PubMed
-
- Adamec R., Head D., Blundell J., Burton P., Berton O. (2006). Lasting Anxiogenic effects of feline predator stress in mice: sex differences in vulnerability to stress and predicting severity of anxiogenic response from the stress experience. Physiol. Behav. 88, 12–29. 10.1016/j.physbeh.2006.03.005 - DOI - PubMed
LinkOut - more resources
Full Text Sources
Miscellaneous