Early-life stress and adult outcomes: Epigenetic, hormonal and neurodevelopmental mechanisms
DOI:
https://doi.org/10.58445/rars.4278Keywords:
cortisol, early-life stress, epigenetic, HPA axis, brain developmentAbstract
Early-life stress (ELS) is a leading risk factor for mental and physical health problems in adulthood, but understanding of the underlying biological mechanisms is nascent. Using evidence from human and animal studies, this review examines three biological mechanisms (i.e., epigenetic modification, hormonal dysregulation, and altered brain development) through which ELS influences adult life. Across these studies, ELS was found to alter stress-regulating genes through epigenetic changes, disrupt cortisol regulation through the hypothalamic-pituitary-adrenal (HPA) axis, and affect the development and functioning of brain regions (e.g., hippocampus, prefrontal cortex, and amygdala). Rather than acting independently, these mechanisms reinforce one another in a cascade. Together, these findings demonstrate that early-life stress becomes biologically embedded in ways that persist in adulthood, highlighting the importance of early intervention and further research into whether these changes can be reversed.
References
Birnie, M. T., & Baram, T. Z. (2025). The evolving neurobiology of early-life stress. Neuron, 113(10), 1474–1490. https://doi.org/10.1016/j.neuron.2025.02.016
Callaghan, B. L., & Richardson, R. (2013). Early experiences and the development of emotional learning systems in rats. Biology of Mood & Anxiety Disorders, 3(1), 8. https://doi.org/10.1186/2045-5380-3-8
Cheng, Z., Su, J., Zhang, K., Jiang, H., & Li, B. (2022). Epigenetic Mechanism of Early Life Stress-Induced Depression: Focus on the Neurotransmitter Systems. Frontiers in Cell and Developmental Biology, 10, 929732. https://doi.org/10.3389/fcell.2022.929732
Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., Aguilar-Gaxiola, S., Alhamzawi, A. O., Alonso, J., Angermeyer, M., Benjet, C., Bromet, E., Chatterji, S., De Girolamo, G., Demyttenaere, K., Fayyad, J., Florescu, S., Gal, G., Gureje, O., … Williams, D. R. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. British Journal of Psychiatry, 197(5), 378–385. https://doi.org/10.1192/bjp.bp.110.080499
Lee, S. H., & Jung, E.-M. (2024). Adverse effects of early-life stress: Focus on the rodent neuroendocrine system. Neural Regeneration Research, 19(2), 336–341. https://doi.org/10.4103/1673-5374.377587
McEwen, B. S., Nasca, C., & Gray, J. D. (2016). Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex. Neuropsychopharmacology, 41(1), 3–23. https://doi.org/10.1038/npp.2015.171
Mousikou, M., Kyriakou, A., & Skordis, N. (2023). Stress and Growth in Children and Adolescents. Hormone Research in Paediatrics, 96(1), 25–33. https://doi.org/10.1159/000521074
Mulligan, C. J. (2025). Epigenetic age acceleration and psychosocial stressors in early childhood. Epigenomics, 17(10), 701–710. https://doi.org/10.1080/17501911.2025.2508684
Pérez, R. F., Santamarina, P., Tejedor, J. R., Urdinguio, R. G., Álvarez-Pitti, J., Redon, P., Fernández, A. F., Fraga, M. F., & Lurbe, E. (2019). Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes. Journal of Translational Medicine, 17(1), 15. https://doi.org/10.1186/s12967-018-1751-9
Shonkoff, J. P., Garner, A. S., THE COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH, COMMITTEE ON EARLY CHILDHOOD, ADOPTION, AND DEPENDENT CARE, AND SECTION ON DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS, Siegel, B. S., Dobbins, M. I., Earls, M. F., Garner, A. S., McGuinn, L., Pascoe, J., & Wood, D. L. (2012). The Lifelong Effects of Early Childhood Adversity and Toxic Stress. Pediatrics, 129(1), e232–e246. https://doi.org/10.1542/peds.2011-2663
Tomoda, A., Nishitani, S., Takiguchi, S., Fujisawa, T. X., Sugiyama, T., & Teicher, M. H. (2025). Review: The neurobiological effects of childhood maltreatment on brain structure, function, and attachment. European Archives of Psychiatry and Clinical Neuroscience, 275(7), 1939–1958. https://doi.org/10.1007/s00406-024-01779-y
Tomoda, A., Polcari, A., Anderson, C. M., & Teicher, M. H. (2012). Reduced Visual Cortex Gray Matter Volume and Thickness in Young Adults Who Witnessed Domestic Violence during Childhood. PLoS ONE, 7(12), e52528. https://doi.org/10.1371/journal.pone.0052528
VanTieghem, M. R., & Tottenham, N. (2017). Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology. In E. Vermetten, D. G. Baker, & V. B. Risbrough (Eds.), Behavioral Neurobiology of PTSD (Vol. 38, pp. 117–136). Springer International Publishing. https://doi.org/10.1007/7854_2016_42
Young, E. S., Doom, J. R., Farrell, A. K., Carlson, E. A., Englund, M. M., Miller, G. E., Gunnar, M. R., Roisman, G. I., & Simpson, J. A. (2021). Life stress and cortisol reactivity: An exploratory analysis of the effects of stress exposure across life on HPA-axis functioning. Development and Psychopathology, 33(1), 301–312. https://doi.org/10.1017/S0954579419001779
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