Epigenetic programming by early-life stress
Open accessAbstract
Studies show that adverse conditions during early life can increase risks of developing mood disorders later in life. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood; a phenomenon often referred to as "early-life programming." Research is addressing the molecular mechanisms underlying this programming by which gene-environment interactions can predispose individuals toward psychopathology. Here we review key findings from animal and clinical studies examining the effects of prenatal and postnatal environment in shaping development of the neuroendocrine regulation of stress and the role of epigenetic mechanisms in translating early-life conditions into long-lasting gene expression changes underpinning stress-related behaviors. We also review latest ideas regarding interactions between environments at different developmental stages and evidence for transgenerational effects. Understanding how prenatal and postnatal experiences can give rise to lasting epigenetic marks conferring increased vulnerability to mental disorders is a major focus of molecular psychiatry and should pave new guidelines for therapeutic interventions.
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Considerable evidence for a lasting impact of stress-associated experiences on gene expression and behavior via epigenetic programming emerges from preclinical models of mental disorders.
“Considerable evidence for a lasting impact of stress-associated experiences on gene expression and behavior via epigenetic programming emerges from a plethora of studies in preclinical models of mental disorders (Alyamani & Murgatroyd, 2018;Kundakovic & Champagne, 2015;Provencal & Binder, 2015)”
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 Alyamani & Murgatroyd, 2018
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1 retracted
Perroud, N., Dayer, A., Piguet, C., Nallet, A., Favre, S., Malafosse, A., & Aubry, J.-M. (2014) · British Journal of Psychiatry · doi:10.1192/bjp.bp.112.120055 · Cited by 89 · see citing works
RetractedEpigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Fetal origins of coronary heart disease
Barker, D. J. P. (1995) · BMJ · doi:10.1136/bmj.311.6998.171 · Cited by 3,570 · see citing works
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531 · see citing works
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181 · see citing works
Developmental plasticity and human health
Bateson, P., Barker, D., Clutton-Brock, T., Deb, D., D'Udine, B., Foley, R. A., Gluckman, P., Godfrey, K., Kirkwood, T., Lahr, M. M., et al. (2004) · Nature · doi:10.1038/nature02725 · Cited by 1,742 · see citing works
Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3275 · Cited by 1,447 · see citing works
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008) · Epigenetics · doi:10.4161/epi.3.2.6034 · Cited by 1,432 · see citing works
Dynamic DNA methylation programs persistent adverse effects of early-life stress
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmühl, Y., Fischer, D., Holsboer, F., Wotjak, C. T., Almeida, O. F. X., & Spengler, D. (2009) · Nature Neuroscience · doi:10.1038/nn.2436 · Cited by 1,162 · see citing works
Self-citationDiscriminative and affective touch: Sensing and feeling.
McGlone, F., Wessberg, J., & Olausson, H. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.001 · Cited by 1,112 · see citing works
Heim, C., & Binder, E. B. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.032 · Cited by 986 · see citing works
Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., Guillaume, S., Mouthon, D., Stouder, C., Dieben, K., et al. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.60 · Cited by 516 · see citing works
Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.013 · Cited by 513 · see citing works
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., & Elbert, T. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.21 · Cited by 511 · see citing works
Genome-wide epigenetic regulation by early-life trauma
Labonté, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., Bureau, A., Mechawar, N., Szyf, M., Meaney, M. J., et al. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.2287 · Cited by 488 · see citing works
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030148 · Cited by 486 · see citing works
Maternal prenatal anxiety and downregulation of placental 11β-HSD2
O’Donnell, K. J., Bugge Jensen, A., Freeman, L., Khalife, N., O’Connor, T. G., & Glover, V. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.09.014 · Cited by 449 · see citing works
Glucocorticoid programming of the fetus; adult phenotypes and molecular mechanisms
Seckl, J. R. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00633-5 · Cited by 392 · see citing works
Lyons‐Ruth, K., Easterbrooks, M. A., & Cibelli, C. D. (1997) · Developmental Psychology · doi:10.1037//0012-1649.33.4.681 · Cited by 388 · see citing works
Lyons-Ruth, K., Easterbrooks, M. A., & Cibelli, C. D. (1997) · Developmental Psychology · doi:10.1037/0012-1649.33.4.681 · Cited by 388 · see citing works
Bertram, C. E., Trowern, A. R., Copin, N., Jackson, A. A., & Whorwood, C. B. (2001) · Endocrinology · doi:10.1210/endo.142.7.8238 · Cited by 385 · see citing works
Peña, C. J., Monk, C. E., & Champagne, F. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039791 · Cited by 377 · see citing works
Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain
McGowan, P. O., Sasaki, A., Huang, T. C. T., Unterberger, A., Suderman, M. J., Ernst, C., Meaney, M. J., Turecki, G., & Moshe Szyf, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002085 · Cited by 372 · see citing works
Hammen, C. L., Shih, J. H., & Brennan, P. A. (2004) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.72.3.511 · Cited by 364 · see citing works
Mulligan, C., D'Errico, N., Stees, J., & Hughes, D. (2012) · Epigenetics · doi:10.4161/epi.21180 · Cited by 342 · see citing works
The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells
Provençal, N., Suderman, M. J., Guillemin, C., Massart, R., Ruggiero, A., Wang, D., Bennett, A. J., Pierre, P. J., Friedman, D. P., Côté, S. M., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1470-12.2012 · Cited by 312 · see citing works
Conradt, E. D., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013) · Epigenetics · doi:10.4161/epi.26634 · Cited by 299 · see citing works
Stewart, P. M., Rogerson, F. M., & Mason, J. I. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.3.7883847 · Cited by 278 · see citing works
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., Schops, G., Dom, M., Van Bree, R., Freson, K., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.03.009 · Cited by 262 · see citing works
Prediction From Low Birth Weight to Female Adolescent Depression
Costello, E. J., Worthman, C. M., Erkanli, A., & Angold, A. C. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.3.338 · Cited by 225 · see citing works
Welberg, L., Thrivikraman, K. V., & Plotsky, P. M. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06374 · Cited by 222 · see citing works
C-tactile afferent stimulating touch carries a positive affective value
Pawling, R., Cannon, P. R., McGlone, F. P., & Walker, S. C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0173457 · Cited by 222 · see citing works
Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities
Melas, P. A., Wei, Y., Wong, C. C. Y., Sjöholm, L. K., Åberg, E., Mill, J., Schalling, M., Forsell, Y., & Lavebratt, C. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000102 · Cited by 220 · see citing works
A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression
Weissman, M. M., Berry, O. O., Warner, V., Gameroff, M. J., Skipper, J., Talati, A., Pilowsky, D. J., & Wickramaratne, P. (2016) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.1586 · Cited by 203 · see citing works
Epigenetics of Early Child Development
Murgatroyd, C., & Spengler, D. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00016 · Cited by 195 · see citing works
Self-citationChildhood abuse is associated with methylation of multiple loci in adult DNA
Suderman, M., Borghol, N., Pappas, J. J., Pinto Pereira, S. M., Pembrey, M., Hertzman, C., Power, C., & Szyf, M. (2014) · BMC Medical Genomics · doi:10.1186/1755-8794-7-13 · Cited by 193 · see citing works
Walker, S. C., Trotter, P. D., Swaney, W. T., Marshall, A. G., & McGlone, F. P. (2017) · Neuropeptides · doi:10.1016/j.npep.2017.01.001 · Cited by 193 · see citing works
Murgatroyd, C., Quinn, J. P., Sharp, H. M., Pickles, A. R., & Hill, J. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.140 · Cited by 168 · see citing works
Self-citationEpigenetic programming of the HPA axis: Early life decides
Murgatroyd, C., & Spengler, D. (2011) · Stress · doi:10.3109/10253890.2011.602146 · Cited by 138 · see citing works
Self-citationTransmitting biological effects of stress in utero: Implications for mother and offspring
Reynolds, R. M., Labad, J., Buß, C., Ghaemmaghami, P., & Räikkönen, K. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.05.018 · Cited by 130 · see citing works
The impact of childhood maltreatment on biological systems: Implications for clinical interventions
González, A. (2013) · Paediatrics & Child Health · doi:10.1093/pch/18.8.415 · Cited by 110 · see citing works
Effects of early life social stress on maternal behavior and neuroendocrinology
Murgatroyd, C., & Nephew, B. C. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.05.020 · Cited by 100 · see citing works
Self-citationTogher, K. L., Togher, K. L., O'Keeffe, M. M., O'Keeffe, M. M., Khashan, A. S., Khashan, A. S., Gutiérrez, H., Gutiérrez, H., Kenny, L. C., Kenny, L. C., et al. (2014) · Epigenetics · doi:10.4161/epi.28703 · Cited by 98 · see citing works
Sharp, H. M., Hill, J., Hellier, J. M., & Pickles, A. R. (2014) · Psychological Medicine · doi:10.1017/s0033291714001342 · Cited by 90 · see citing works
Provençal, N., Suderman, M. J., Guillemin, C., Vitaro, F., Côté, S. M., Hallett, M., Tremblay, R. E., & Szyf, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089839 · Cited by 85 · see citing works
Activation of hypothalamic oxytocin neurons following tactile stimuli in rats
Okabe, S., Yoshida, M., Takayanagi, Y., & Onaka, T. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.05.055 · Cited by 82 · see citing works
Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior
Appleton, A. A., Lester, B. M., Armstrong, D. A., Lesseur, C., & Marsit, C. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.11.004 · Cited by 72 · see citing works
Pettit, J. W., Olino, T. M., ROBERTS, R. E., Seeley, J. R., & Lewinsohn, P. M. (2008) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374410802148129 · Cited by 66 · see citing works
Pickles, A. R., Sharp, H. M., Hellier, J. M., & Hill, J. (2016) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-016-0886-6 · Cited by 66 · see citing works
Early life trauma, depression and the glucocorticoid receptor gene—An epigenetic perspective
Smart, C., Strathdee, G., Watson, S., Murgatroyd, C., & McAllister-Williams, R. H. (2015) · Psychological Medicine · doi:10.1017/s0033291715001555 · Cited by 61 · see citing works
Self-citationPolycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer
Murgatroyd, C., & Spengler, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090277 · Cited by 44 · see citing works
Self-citationOLINO, T. M., PETTIT, J. W., KLEIN, D. N., ALLEN, N. B., SEELEY, J. R., & LEWINSOHN, P. M. (2008) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e31815a6ae6 · Cited by 42 · see citing works
Babb, J. A., Deligiannidis, K. M., Murgatroyd, C., & Nephew, B. C. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.03.039 · Cited by 31 · see citing works
Self-citation(2014) · Elsevier eBooks · doi:10.1016/c2013-0-00061-8 · Cited by 30 · see citing works
Doherty, T. S., & Roth, T. L. (2016) · Development and Psychopathology · doi:10.1017/s095457941600081x · Cited by 26 · see citing works
Epigenetics, the Environment, and Children’s Health Across Lifespans
Hollar, D. (2016) · Springer eBooks · doi:10.1007/978-3-319-25325-1 · Cited by 24 · see citing works
Murgatroyd, C., Hicks-Nelson, A., Fink, A., Beamer, G., Gurel, K., Elnady, F., Pittet, F., & Nephew, B. C. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00155 · Cited by 22 · see citing works
Self-citationTransgenerational Social Stress, Immune Factors, Hormones, and Social Behavior
Murgatroyd, C., Babb, J. A., Bradburn, S., Carini, L. M., Beamer, G., & Nephew, B. C. (2016) · Frontiers in Ecology and Evolution · doi:10.3389/fevo.2015.00149 · Cited by 16 · see citing works
Self-citationAbdolmaleky, H. M., Glatt, S. J., & Tsuang, M. T. (2011) · Springer eBooks · doi:10.1007/978-1-84882-644-1_11 · Cited by 12 · see citing works
Gomez, S., Diawara, A., Gbeha, E., Awadalla, P., Sanni, A., Idaghdour, Y., & Rahimy, M. C. (2016) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00008 · Cited by 10 · see citing works
Translational Animal Models for the Study of Epigenetics and the Environment
Murgatroyd, C., & Bradburn, S. (2016) · Springer eBooks · doi:10.1007/978-3-319-25325-1_8 · Cited by 7 · see citing works
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Research works printed but not linked: 2
- Murgatroyd, C. & Spengler, D., 2011c. Epigenetics of early child development. Frontiers in psychiatry, 2, p.16. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21647402 [Accessed June 22, 2016].
- National Research Council (US) and Institute of Medicine (US) Committee on Depression, P.P. and the H.D. of C., England, M.J. & Sim, L.J., 2009. Depression in Parents, Parenting, and Children, National Academies Press (US). Available at: http://www.ncbi.nlm.nih.gov/pubmed/25009931 [Accessed August 12, 2016].
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Schiele, M. A., Gottschalk, M. G., & Domschke, K. (2020) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101830 · Cited by 156 · see citing works
Cell-type-specific epigenetic effects of early life stress on the brain
Rahman, M. F., & McGowan, P. O. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02076-9 · Cited by 75 · see citing works
- Authors
- Alyamani, R. A. S., & Murgatroyd, C.
- Affiliations
- Manchester Metropolitan University (GB)
- Corresponding author
- Murgatroyd, Chris
- Venue
- Progress in Molecular Biology and Translational Science
- Publisher
- Elsevier
- Published
- 2018
- Volume
- 157
- Pages
- 133-150
- ISSN
- 1877-1173 (ISSN-L)
- OpenAlex
- W2803589075
- Cited by
- 76
- References
- 61
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 41 · 2021: 8 · 2020: 6 · 2019: 2
- FWCI
- 9.33
- Type
- book chapter
- Language
- en
- Open access
- green
- e-space.mmu.ac.uk
- Locations
- Progress in molecular biology and translational science (publishedVersion)
- PubMed (publishedVersion)
- e-space (Manchester Metropolitan University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- early life stress, epigenetic programming, gene-environment interaction, intrauterine environment, postnatal environment, stress responsivity, mood disorders, transgenerational effects, epigenetic modifications, animal models of stress
- MeSH terms
- Animals, Family Characteristics, Humans, Stress, Psychological, Biomarkers, DNA Methylation, Epigenesis, Genetic
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