Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study

Minae Niwa; Sedona Lockhart; Daniel J Wood; Kun Yang; Jose Francis-Oliveira; Kyohei Kin; Adeel Ahmed; Gary S Wand; Shin-Ichi Kano; Jennifer L Payne; Akira Sawa

doi:10.1038/s44220-024-00217-1

Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study

Nat Ment Health. 2024 May;2(5):593-604. doi: 10.1038/s44220-024-00217-1. Epub 2024 Apr 11.

Authors

Minae Niwa^{1

2

3

4}, Sedona Lockhart¹, Daniel J Wood¹, Kun Yang¹, Jose Francis-Oliveira², Kyohei Kin², Adeel Ahmed², Gary S Wand⁵, Shin-Ichi Kano^{1

2

3}, Jennifer L Payne^{1

6}, Akira Sawa^{1

7

8

9

10

11}

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
³ Department of Neurobiology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
⁴ Department of Biomedical Engineering, University of Alabama at Birmingham School of Engineering, Birmingham, AL, USA.
⁵ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlotte, VA, USA.
⁷ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Abstract

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans. Adolescent social isolation prolonged glucocorticoid elevation, leading to long-lasting postpartum behavioral changes in female mice. These changes were unresponsive to current PPD treatments but improved with post-delivery glucocorticoid receptor antagonist treatment. Childhood/adolescent stress significantly impacted HPA axis dysregulation and PPD in human females. Repurposing glucocorticoid receptor antagonists for some cases of treatment-resistant PPD may be considered.

Abstract

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