Abstract
Rationale
Women with premenstrual dysphoric disorder (PMDD) appear to have altered central nervous system sensitivity to neuroactive steroid hormones, manifesting as affective symptoms and heightened arousal in the luteal phase of the menstrual cycle. In particular, women with PMDD appear less sensitive to allopregnanolone, a positive allosteric GABA-A receptor (GABA-A-R) modulator.
Objectives
This study evaluated psychophysiologic reactivity in women with PMDD in the follicular and luteal phases of the menstrual cycle, utilizing anxiety-potentiated startle (APS), a potential translational marker of GABA-A-R sensitivity. The study also assessed APS response to low-dose sertraline treatment in women with PMDD.
Methods
Participants’ APS and fear-potentiated startle (FPS) were assessed in the follicular and luteal phases. Women with PMDD received 50 mg sertraline in the following luteal phase to examine impact on APS and FPS.
Results
There were no significant differences between controls (n = 41) and PMDD participants (n = 36) in change from follicular to luteal phases in baseline startle, APS nor FPS. However, among participants who responded to sertraline, APS was higher in the untreated luteal phase than the follicular phase, but lower in the treated luteal phase than the follicular phase.
Conclusion
These data demonstrate elevated psychophysiologic arousal in the luteal phase among some women with PMDD, suggesting impaired ability to modulate arousal reactivity. Specifically, alterations in APS suggest potential GABA-A-R changes across the menstrual cycle and in response to sertraline among treatment responders.
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Acknowledgements
We would like to acknowledge Carla Golden, Jeanette Bradley, Joanna Marks, and Rachel Brooks for assistance in coordinating the study; Dina Appleby and Brendan McGeehan for database management; and Carrie Malanga, RN, PMHNP-BC, and Debora Dunbar MSN, CRNP, ANP-BC, for phlebotomy support.
Funding
This work was supported by the National Institutes of Health (K23 MH107831; Hantsoo) and the Brain and Behavior Research Foundation (NARSAD Young Investigator Award; Hantsoo).
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Hantsoo, L., Grillon, C., Sammel, M. et al. Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder. Psychopharmacology 238, 2985–2997 (2021). https://doi.org/10.1007/s00213-021-05916-6
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DOI: https://doi.org/10.1007/s00213-021-05916-6