# Distinct Steroid Mechanisms in Menstrual Cycle Exacerbation of Psychopathology

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $626,323

## Abstract

SUMMARY
Changes in reproductive hormones across the menstrual cycle may be a key biological source of symptom
variability in psychopathology. Strong individual differences in neural sensitivity to normal hormone changes
can result lability of a wide range of emotional, interpersonal, and behavioral symptoms; however, the
biobehavioral mechanisms underlying these effects are not yet well understood. Borderline personality disorder
(BPD) is a severe and costly psychiatric condition comprising labile symptoms across many domains of
functioning. Our pilot data suggest three distinct biologically based mechanisms may produce cycle-based
symptom exacerbation, contributing to symptom lability: 1) reactive and interpersonal symptoms due to
irritability from changes in progesterone (P4) levels, 2) depressive symptoms due to impaired cognitive
functioning and increased rumination during estrogen (E2) withdrawal, and 3) risk-taking symptoms due
increased reward responsiveness during E2 peaks (ovulation). The objectives of this research are to test a
model of three RDoC-consistent biologically-based mechanisms underlying how the menstrual cycle
exacerbates psychopathology. A sample of 170 women ages 18 to 45 with ≥3 BPD symptoms will be recruited
from specialized clinical services and social media. Participants will be comprehensively assessed for BPD and
exclusion criteria (e.g., use of hormone-based medication or hormonal conditions). Participants will complete
well-established assessment measures of BPD and other psychopathological symptoms and diagnoses during
a baseline laboratory visit within the within the first few days of the start of their menstrual cycle. Then, they will
provide complete questionnaires about BPD symptoms and proposed mechanisms every evening for two
complete cycles. During one cycle, they will complete tasks targeted to key cycle phases, based on menses
onset and ovulation test results, and daily urine samples for hormone assay each morning. Specific Aims.
Aim 1 is to evaluate whether shifts in hormones across cycle predict within-person changes in symptoms
consistent with proposed triadic hormone sensitivity theory, with rising levels of P4 predicting increases in
rejection sensitivity, interpersonal conflict, and impulsive reactivity to stress, decreasing levels of E2 predicting
increases in depression, hopelessness, and suicidal ideation, and peaks in E2 (ovulation) predicting increases
in proactive aggression and substance misuse. Aim 2 is to evaluate whether proposed psychological
mechanisms mediation associations between hormonal changes and symptom effects, with increased
irritability expected to mediate P4 effects, decreased cognitive functioning expected to mediate E2 withdrawal
effects, especially for individuals with greater rumination-proneness, and increased reward responsiveness
expected to mediate ovulatory effects. An exploratory Aim 3 will examine the extent to which presence of these
three forms of hormone sensit...

## Key facts

- **NIH application ID:** 10451805
- **Project number:** 5R01MH126940-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Jessica Rachael Peters
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $626,323
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451805

## Citation

> US National Institutes of Health, RePORTER application 10451805, Distinct Steroid Mechanisms in Menstrual Cycle Exacerbation of Psychopathology (5R01MH126940-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10451805. Licensed CC0.

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