Scientific Poster Session IV - Original Research

Abstract

Women with premenstrual dysphoric disorder (PMDD) commonly self-report inability to control their stress levels. However, it is not clear whether the hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in PMDD.

Research Question or Hypothesis: Does the trajectory of cortisol output differ in women with PMDD from healthy controls? Is the trajectory modified by allopregnanolone?

Study Design: Human laboratory study.

Methods:

We recruited women who did not take medications, smoke, or consume illicit drugs, and who were free of other psychiatric conditions to provide their daily symptom ratings across 2-3 menstrual cycles, based on which we classified them as PMDD (n=16) or healthy controls (n=16). In the last menstrual cycle of the study, they underwent the Trier Social Stress Test procedure, throughout which we collected serum samples of cortisol and allopregnanolone, which we analyzed using ultra-performance liquid chromatography tandem mass spectrometry. We constructed linear mixed effects models in R to study changes in cortisol concentrations, with allopregnanolone, time, and diagnosis interaction included as fixed effects, and individual participants as random effects.

Results: Cortisol output in response to acute stress challenge was blunted in the PMDD participants (F_(6,142.4)=2.64;p=0.018), and the 3-way interaction between allopregnanolone, time, and diagnosis was statistically significant (F_(6,142.4)= 2.50; p=0.024). A further examination of the 3-way interaction showed that the neutral relationship between allopregnanolone and cortisol at baseline in the healthy control participants turned negative through the course of stress. The slope of the relationship between cortisol and allopregnanolone remained unchanged.

Conclusion:

While healthy women are able to flexibly modify their HPA axis during stress as a function of their circulating allopregnanolone, women with PMDD have a blunted HPA axis that is insensitive to the effects of allopregnanolone. The present study details how tolerance to allopregnanolone in PMDD emerges in the study of the HPA function during acute stress.

Presenting Author

Authors