Genes learn from stress: How infantile trauma programs us for depression
Open accessAbstract
Early-life stress induces persistent memory traces on our genes and programs the life-long risk for depression. Epigenetic marking of the arginine vasopressin (AVP) gene by early-life stress in mice underpins sustained expression and increased hypothalamic-pituitary-adrenal axis activity, triggering endocrine and behavioral alterations that are frequent features in depression. This epigenetic memory evolves in two steps coordinated by the epigenetic reader and writer MeCP2. While early derepression of AVP is driven by neuronal activity causing Ca2+/calmodulin kinase-dependent phosphorylation and dissociation of MeCP2, subsequent hypomethylation at the AVP enhancer gradually develops to sustain derepression. In a vicious circle MeCP2 occupancy uncouples from the initial stimulus and leads to the hard-coding of early-life experience at the level of DNA methylation. The sequential order of these events demarcates the transition from a preliminary to a persistent, possibly irreversible, epigenetic memory and thus defines a critical time window for the timely therapy of severe trauma.
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Emerging epigenetic research suggests that timing of stress may be linked to functional alterations of genes implicated in depression.
“emerging epigenetic research suggests that timing of stress may be linked to functional alterations of genes implicated in depression (Murgatroyd et al. 2010).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Murgatroyd et al. 2010
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“Although a survey of epigenetic methods and findings is outside the scope of this review, emerging epigenetic research suggests that timing of stress may be linked to functional alterations of genes implicated in depression (Murgatroyd et al. 2010).”
Backgroundvan der Knaap, L. J., Riese, H., Hudziak, J. J., Verbiest, M. M. P. J., Verhulst, F. C., Oldehinkel, A. J., & van Oort, F. V. A. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.22 · Cited by 165 · see citing works
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Epigenetic programming of the HPA axis: Early life decides
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Self-citationTraumatic stress and human DNA methylation: A critical review
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Interaction of Stress, Corticotropin-Releasing Factor, Arginine Vasopressin and Behaviour
Beurel, E., & Nemeroff, C. B. (2014) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2014_306 · Cited by 64 · see citing works
Environmental epigenomics: understanding the effects of parental care on the epigenome
McGowan, P. O., & Szyf, M. (2010) · Essays in Biochemistry · doi:10.1042/bse0480275 · Cited by 39 · see citing works
- Authors
- Murgatroyd, C., Wu, Y., Bockmühl, Y., & Spengler, D.
- Affiliations
- Max Planck Society (DE)
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Spengler, Dietmar
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2010-04
- Volume
- 5
- Issue
- 3
- Pages
- 194-199
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- OpenAlex
- W2010659314
- Cited by
- 114
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 7 · 2015: 11 · 2014: 10 · 2013: 7 · 2012: 21
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Epigenetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Commission
- 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
- early life stress, depression, vasopressin, DNA methylation, MeCP2, epigenetic memory, hypothalamic-pituitary-adrenal axis, calcium/calmodulin-dependent protein kinase, trauma
- MeSH terms
- Animals, Depression, Humans, Neurophysins, Phosphorylation, Pituitary-Adrenal System, Protein Precursors, Stress, Physiological, Vasopressins, Calcium-Calmodulin-Dependent Protein Kinases, Genetic Predisposition to Disease, Epigenesis, Genetic, Methyl-CpG-Binding Protein 2, Gene-Environment Interaction
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