4.4 Article

Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder

Journal

PSYCHOPHARMACOLOGY
Volume 238, Issue 10, Pages 2985-2997

Publisher

SPRINGER
DOI: 10.1007/s00213-021-05916-6

Keywords

Premenstrual; Menstrual cycle; Depression; Acoustic startle response; GABA; Neuroactive steroid; Progesterone

Funding

  1. National Institutes of Health [K23 MH107831]
  2. Brain and Behavior Research Foundation (NARSAD Young Investigator Award)

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This study found 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.
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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