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Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk

  • Liisa Hantsoo
    Correspondence
    Address correspondence to Liisa Hantsoo, Ph.D., Department of Psychiatry, University of Pennsylvania School of Medicine, 3535 Market Street, Philadelphia, PA 19104.
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Sara Kornfield
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Montserrat C. Anguera
    Affiliations
    Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • C. Neill Epperson
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Penn PROMOTES Research on Sex and Gender in Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Published:September 04, 2018DOI:https://doi.org/10.1016/j.biopsych.2018.08.018

      Abstract

      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.

      Keywords

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