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Temporal dynamics of neurobehavioral hormone sensitivity in a scaled-down experimental model of early pregnancy and parturition

Neuropsychopharmacology volume 49, pages 414–421 (2024)Cite this article

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Abstract

The hormonal changes of pregnancy and parturition can trigger robust changes in affective state, particularly among patients with a history of postpartum depression. However, more work is needed to elucidate the temporal dynamics of symptom emergence. The current study explored how quickly hormone-sensitive (HS+) individuals can be differentiated from hormone-insensitive (HS−) controls in the context of a tightly controlled experimental hormone manipulation, and which symptoms demonstrate the most rapid, consistent, and largest response during this protocol. Participants were female, non-pregnant, and euthymic, with a history of DSM-5 major depressive episode with peripartum onset (n = 15) or parous healthy controls with no psychiatric history (n = 15). Perinatal hormonal changes were simulated by inducing hypogonadism, adding back estradiol (E2) and progesterone (P4) to reach first-trimester levels for 8 weeks, and then subsequently withdrawing both hormones. Those reporting a 30% or greater increase during addback or withdrawal on select subscales of the Inventory of Depression and Anxiety Symptoms (IDAS) were identified as HS+. Participants provided daily ratings of symptoms throughout the study via the Daily Record of Severity of Problems. Results indicated that HS+ participants could be differentiated from HS− participants early in the hormone protocol, with many symptoms showing significantly greater change from baseline within the first week of addback. Notably, the most rapid symptom increases were observed for Anger/Irritability, Mood Swings, Overwhelm, Lethargy, Increased Appetite, Joint and Muscle Pain, and Breast Tenderness, reaching 50% of peak group contrast within the first week of hormone addback. The largest group effects were observed for Anger/Irritability, followed by Fatigue and Anxiety, and the most consistent group effects were observed for Anger/Irritability, Interpersonal Conflict, Overwhelm, and Hopelessness. Findings support the role of reproductive hormones in the onset of perinatal affective disorders. The rapid emergence of anger and irritability in HS+ participants suggests that these symptoms may be early indicators of perinatal hormone sensitivity.

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Fig. 1: Depiction of mean change from baseline by hormone sensitivity group for the total score.
Fig. 2: Outcomes across experimental weeks by group.
Fig. 3

Notes

  1. We use this term to refer to cisgender women and other individuals who experience the hormonal fluctuations associated with the female reproductive system, regardless of gender identity or expression.

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Acknowledgements

The authors thank the individuals who participated in this project and made this research possible.

Funding

This research was supported by funding from the Foundation of Hope (CES), Brain & Behavior Research Foundation (CES), NIH R21MH101409 (DRR and CES), NIH T32MH093315 (DRR), NIH R01MH122446 (TEM), NIH RF1MH120843 (TEM) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002489 (DRR). Author DAS is supported by T32MH093315. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The sponsors had no input into the study design; collection, analysis or interpretation of the data; in writing the report; or in the decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Tory Eisenlohr-Moul

  2. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Tory Eisenlohr-Moul, Danielle A. Swales, David R. Rubinow & Crystal E. Schiller

  3. Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Lauren Schiff

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Contributions

CES and DRR designed the study and oversaw the collection of study data. LS advised on the hormone administration and participant eligibility and oversaw participant safety. TEM refined hypotheses, completed data analyses, and wrote the first draft of the manuscript. DAS assisted in data analyses and manuscript preparation. All authors assisted in results and have contributed to and approved the final manuscript.

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Correspondence to Tory Eisenlohr-Moul.

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Eisenlohr-Moul, T., Swales, D.A., Rubinow, D.R. et al. Temporal dynamics of neurobehavioral hormone sensitivity in a scaled-down experimental model of early pregnancy and parturition. Neuropsychopharmacol. 49, 414–421 (2024). https://doi.org/10.1038/s41386-023-01687-0

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