The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions

Liisa Hantsoo, Kathleen M. Jagodnik, Andrew M. Novick, Ritika Baweja, Teresa Lanza di Scalea, Aysegul Ozerdem, Erin C. McGlade, Diana I. Simeonova, Sharon Dekel, Sara L. Kornfield, Michelle Nazareth, Sandra J. Weiss

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder [PMDD]), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women’s mental health as it pertains to pathophysiology, early diagnosis, and treatment targets.

Original languageEnglish
Article number1295261
JournalFrontiers in Endocrinology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2023 Hantsoo, Jagodnik, Novick, Baweja, di Scalea, Ozerdem, McGlade, Simeonova, Dekel, Kornfield, Nazareth and Weiss.

Funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. LH: R21 MH125936. KJ: Mortimer B. Zuckerman STEM Leadership Postdoctoral Fellowship. AN: K23 HD110435. EM: ABCD Utah Site 5U01DA041134-09; Department of Veterans Affairs Mental Illness Research, Education, and Clinical Centers; Western Institute of Veterans Research (WIVR). DS: NIMH K23 MH096042, Brain & Behavior Research Foundation. SD: NICHD R01HD108619, NICHD R03HD101724. SW: NIH R01 HD102604, NIH R01 HD081188, Robert and Delphine Wentland Eschbach Endowment.

FundersFunder number
Delphine Wentland Eschbach Endowment
Department of Veterans Affairs Mental Illness Research, Education, and Clinical Centers
Western Institute of Veterans Research
National Institutes of HealthR01 HD081188, R01 HD102604
National Institute of Mental HealthK23 MH096042
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentR03HD101724, R01HD108619

    Keywords

    • depression
    • female
    • hypothalamic-pituitary-adrenal (HPA) axis
    • perimenopause
    • peripartum
    • premenstrual
    • stress
    • trauma

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