Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk
Open accessAbstract
During pregnancy, programming of the fetal central nervous system establishes vulnerabilities for emergence of neuropsychiatric phenotypes later in life. Psychosocial influences during pregnancy, such as stressful life events and chronic stress, correlate with offspring neuropsychiatric disorders and inflammation, respectively. Stress promotes inflammation, but the role of inflammation as a mediator between maternal psychosocial stress and offspring neuropsychiatric outcomes has not been extensively studied in humans. This review summarizes clinical evidence linking specific types of stress to maternal inflammatory load during pregnancy. We propose that inflammation is a mediator in the relationship between psychosocial stress and offspring neuropsychiatric outcomes, potentially influenced by poor maternal glucocorticoid-immune coordination. We present relevant experimental animal research supporting this hypothesis. We conclude that clinical and preclinical research supports the premise that stress-induced maternal immune activation contributes in part to prenatal programming of risk. Programming of risk is likely due to a combination of vulnerabilities, including multiple or repeated inflammatory events; timing of such events; poor maternal regulation of inflammation; genetic vulnerability; and lifestyle contributors.
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Maternal inflammation may play a role, given that maternal stress has been associated with increased inflammatory markers and altered cytokine production during pregnancy.
“Moreover, maternal inflammation may play a role, given that maternal stress has been associated with increased inflammatory markers and altered cytokine production during pregnancy [136–139].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [137]
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Davies, C., Segre, G., Estradé, A., Radua, J., De Micheli, A., Provenzani, U., Oliver, D., Salazar de Pablo, G., Ramella-Cravaro, V., Besozzi, M., et al. (2020) · The Lancet Psychiatry · doi:10.1016/s2215-0366(20)30057-2 · Cited by 301 · see citing works
Wu, Y., Lu, Y.-C., Jacobs, M., Pradhan, S., Kapse, K., Zhao, L., Niforatos-Andescavage, N., Vezina, G., du Plessis, A. J., & Limperopoulos, C. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.19940 · Cited by 218 · see citing works
Wu, Y., De Asis-Cruz, J., & Limperopoulos, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02449-0 · Cited by 124 · see citing works
Positive maternal mental health, parenting, and child development
Phua, D. Y., Kee, M. Z. L., & Meaney, M. J. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.09.028 · Cited by 124 · see citing works
Zhao, Q., Dai, W., Chen, H. Y., Jacobs, R. E., Zlokovic, B. V., Lund, B. T., Montagne, A., & Bonnin, A. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113310119 · Cited by 52 · see citing works
- Authors
- Hantsoo, L., Kornfield, S., Anguera, M. C., & Epperson, C. N.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hantsoo, Liisa
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 85
- Issue
- 2
- Pages
- 97-106
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6309506
- OpenAlex
- W2890036014
- Cited by
- 269
- References
- 147
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 39 · 2023: 69 · 2022: 31 · 2021: 50 · 2020: 27 · 2019: 11 · 2018: 1
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23MH107831, K23MH102360, P50 MH099910)
- National Institute of Allergy and Infectious Diseases (AI124084)
- Office of Research on Women's Health (MH099919, K12HD085848)
- Brain and Behavior Research Foundation
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- maternal stress, inflammation, maternal immune activation, prenatal programming, psychosocial stress, fetal central nervous system development, chronic stress, life events, genetic susceptibility
- MeSH terms
- Animals, Mental Disorders, Female, Humans, Immune System, Inflammation, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Psychological
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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