Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice

Kathleen E. Morrison, C. Neill Epperson, Mary D. Sammel, Grace Ewing, Jessica S. Podcasy, Liisa Hantsoo, Deborah R. Kim, Tracy L. Bale

Research output: Contribution to journalArticle

Abstract

Background Adverse childhood experiences (ACEs) are one of the greatest predictors of affective disorders for women. Periods of dynamic hormonal flux, including pregnancy, exacerbate the risk for affective disturbance and promote hypothalamic-pituitary-adrenal (HPA) axis dysregulation, a key feature of affective disorders. Little is understood as to how stress experienced in late childhood, defined as preadolescence, alters the programming unique to this period of brain maturation and its interaction with the hormonal changes of pregnancy and postpartum. Methods Preadolescent female mice were exposed to chronic stress and examined for changes in their HPA axis during pregnancy and postpartum, including assessment of maternal-specific stress responsiveness and transcriptomics of the paraventricular nucleus of the hypothalamus. Translationally, pregnant women with low or high ACEs were examined for their maternal stress responsiveness. Results As predicted, preadolescent stress in mice resulted in a significant blunting of the corticosterone response during pregnancy. Transcriptomic analysis of the paraventricular nucleus revealed widespread changes in expression of immediate early genes and their targets, supporting the likely involvement of an upstream epigenetic mechanism. Critically, in our human studies, the high ACE women showed a significant blunting of the HPA response. Conclusions This unique mouse model recapitulates a clinical outcome of a hyporesponsive HPA stress axis, an important feature of affective disorders, during a dynamic hormonal period, and suggests involvement of transcriptional regulation in the hypothalamus. These studies identify a novel mouse model of female ACEs that can be used to examine how additional life adversity may provoke disease risk or resilience.

Original languageEnglish (US)
Pages (from-to)693-701
Number of pages9
JournalBiological psychiatry
Volume81
Issue number8
DOIs
StatePublished - Apr 15 2017

Keywords

  • Adolescence
  • HPA axis
  • Paraventricular nucleus
  • Postpartum
  • Pregnancy
  • Stress

ASJC Scopus subject areas

  • Biological Psychiatry

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  • Cite this

    Morrison, K. E., Epperson, C. N., Sammel, M. D., Ewing, G., Podcasy, J. S., Hantsoo, L., Kim, D. R., & Bale, T. L. (2017). Preadolescent Adversity Programs a Disrupted Maternal Stress Reactivity in Humans and Mice. Biological psychiatry, 81(8), 693-701. https://doi.org/10.1016/j.biopsych.2016.08.027