Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress
Open accessAbstract
Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61-67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (P<0.001): methylation increased from pre- to post-stress (P=0.009) and decreased from post-stress to follow-up (P<0.001). This decrease was also found in a second target sequence of OXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR-which may in part reflect changes in blood cell composition-but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders.
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No such changes were detectable for BDNF exon 6 methylation.
“No such changes were detectable for BDNF exon 6 methylation, highlighting the importance to evaluate the short-term and long-term temporal dynamics of epigenetic modifications in light of potentially adverse environmental influences (Unternaehrer et al., 2012).”
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 Unternaehrer et al., 2012
The DNA methylation analysis section identifies the assessed BDNF target as near exon VI. The Results (Methylation of BDNF) report no overall change in mean methylation and no significant post-hoc contrast, but they do report a significant time effect in 1 of 10 CpG units. Thus, the claim holds for mean methylation, not for every measured site. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPsychosocial stress significantly increases whole blood methylation of OXTR exon 3 in an acute post-stress phase (15 minutes past challenge) and significantly decreases methylation, even below pre-stress baseline, in a follow-up phase (90 minutes past challenge) in 76 adults.
“psychosocial stress has been demonstrated to significantly increase whole blood methylation of OXTR exon 3 in an acute post-stress phase (15 minutespast challenge) and to significantly decrease methylation, even below the point of pre-stress baseline methylation, in a follow-up phase (90 minutespast challenge) in 76 adults (Unternaehrer et al., 2012).”
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 Unternaehrer et al., 2012
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Experimental — accuracy not yet measuredThe Trier Social Stress Test has been associated with dynamic DNA methylation alterations in a stress-associated gene within 90 min after exposure.
“Furthermore, an experimental psychological stressor, the Trier Social Stress Test, has shown to be associated with dynamic DNAm alterations in a stress-associated gene within 90 min after exposure [11].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [11]
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- Authors
- Unternaehrer, E., Luers, P., Mill, J., Dempster, E., Meyer, A. H., Staehli, S., Lieb, R., Hellhammer, D. H., & Meinlschmidt, G.
- Affiliations
- Universität Trier (DE)
- King's College London (GB)
- University of Basel (CH)
- Corresponding author
- Meinlschmidt, G
- Venue
- Translational Psychiatry
- Published
- 2012-08-14
- Volume
- 2
- Issue
- 8
- Pages
- e150-e150
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3432191
- OpenAlex
- W2132152083
- Cited by
- 250
- References
- 72
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 5 · 2023: 15 · 2022: 15 · 2021: 14 · 2020: 18 · 2019: 18 · 2018: 25 · 2017: 20 · 2016: 36 · 2015: 19 · 2014: 27 · 2013: 18
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel) (submittedVersion)
- KOPS (University of Konstanz) (submittedVersion, cc-by-nc-nd)
- edoc (University of Basel)
- Funders
- National Science Foundation
- King's College London
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (104890, 100014, 135328)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- DNA methylation, acute psychosocial stress, oxytocin receptor, brain-derived neurotrophic factor, Trier Social Stress Test, epigenetics, blood cell composition, mental illness, aging
- MeSH terms
- Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Stress, Psychological, Receptors, Oxytocin, CpG Islands, DNA Methylation, Brain-Derived Neurotrophic Factor, Epigenomics
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