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Translating basic research knowledge on the biological embedding of early-life stress into novel approaches for the developmental programming of lifelong health
Open accessAbstract
This review integrates scientific knowledge obtained over the past few decades on the biological mechanisms that contribute to the profound association between exposure to early adversity, including childhood trauma and prenatal stress, and the lifelong elevated risk to develop a broad range of diseases. We further discuss insights into gene-environment interactions moderating the association between early adversity and disease manifestation and we discuss the role of epigenetic and other molecular processes in the biological embedding of early adversity. Based on these findings, we propose potential mechanisms that may contribute to the intergenerational transmission of risk related to early adversity from the mother to the fetus. Finally, we argue that basic research knowledge on the biological embedding of early adversity must now be translated into novel intervention strategies that are mechanism-driven and sensitive to developmental timing. Indeed, to date, there are no diagnostic biomarkers of risk or mechanism-informed interventions that we can offer to victims of early adversity in order to efficiently prevent or reverse adverse health outcomes. Such translational efforts can be expected to have significant impact on both clinical practice and the public health system, and will promote precision medicine in pediatrics and across the lifespan.
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“This is probably because health conditions associated with early life stress often occur or are aggravated in response to acute stressors in individuals with dysfunctional stress response, which includes changed neurohumoral regulation of the hypothalamic–pituitary–adrenal axis and increased autonomic and inflammatory response [14, 21, 22].”
From Associations of childhood trauma with long-term diseases and alcohol and nicotine use disorders in Czech and Slovak representative samples (2022) · cites this paper as [14]
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Metadata
- Authors
- Heim, C. M., Entringer, S., & Buss, C.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Entringer, Sonja
- Buss, Claudia
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 105
- Pages
- 123-137
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC6561839
- OpenAlex
- W2905562542
- Cited by
- 158
- References
- 227
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 18 · 2023: 25 · 2022: 35 · 2021: 21 · 2020: 18 · 2019: 7
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01KR1301, 01GL1743)
- Deutsche Forschungsgemeinschaft (EXC257, EN 851/2-1)
- European Research Council (ERC 639766, ERC 678073)
- U.S. Public Health Service
- National Institutes of Health (P50 HD-551411, 5UG3OD023349, R01 HD-065825, R01 AG-050455, R01 MH-105538, R01 HD-060628, MH 58922)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- early life stress, biological embedding, developmental programming, childhood trauma, prenatal stress, gene-environment interaction, epigenetics, intergenerational transmission, mother-to-child transmission, precision medicine, developmental timing, disease risk
- MeSH terms
- Psychological Trauma, Adverse Childhood Experiences, Animals, Brain, Female, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Psychological, Epigenesis, Genetic, Telomere Shortening, Gene-Environment Interaction
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