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Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep quality and negative affect in pregnancy: a pilot study

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Abstract

Rationale

Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy.

Objectives

Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy.

Methods

Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior.

Results

Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated.

Conclusions

These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses.

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Acknowledgments

This research was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant award number 1UL1TR001111, NIH grant T32-MH09331, and a grant from the Foundation of Hope for the Research and Treatment of Mental Illness. In addition, Dr. Schiller was supported by the UNC Building Interdisciplinary Careers in Women’s Health (BIRCWH) Career Development Program (K12 HD001441), and Dr. Stuebe was supported by NIH grant R01HD073220. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors would like to thank Chihiro Christmas, Samantha Nau, Carissa Cartelli, Andrea Ramirez, Pallavi Surana, Audra Goldstein, Ariana Rivens, Danyelle Dawson, Julia Paulson, and Khanh Nguyen for their help with data collection for the study.

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Authors and Affiliations

  1. Department of Psychiatry, CB#7175, UNC School of Medicine, Psychiatry Wing C, Chapel Hill, NC, 27599-7175, USA

    Shannon K. Crowley, Crystal E. Schiller, A. Leslie Morrow & Susan S. Girdler

  2. Bowles Center for Alcohol Studies, Chapel Hill, NC, 27599-7175, USA

    Todd K. O’Buckley & A. Leslie Morrow

  3. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Chapel Hill, NC, 27599-7175, USA

    Alison Stuebe

  4. Department of Maternal and Child Health, Gillings School of Global Public Health, Chapel Hill, NC, 27599-7175, USA

    Alison Stuebe

  5. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7175, USA

    A. Leslie Morrow

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  1. Shannon K. Crowley
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  2. Todd K. O’Buckley
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Correspondence to Susan S. Girdler.

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Crowley, S.K., O’Buckley, T.K., Schiller, C.E. et al. Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep quality and negative affect in pregnancy: a pilot study. Psychopharmacology 233, 1299–1310 (2016). https://doi.org/10.1007/s00213-016-4217-x

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