Identification and Validation of Epigenetic Biomarkers of PMDD

Not yet recruiting

• Conditions: PMDD; Premenstrual Dysphoric Disorder (PMDD); Premenstrual Syndrome-PMS; Premenstrual Syndrome; Menstrual Cycle

• Registration Number: NCT06771583
• Lead Sponsor: Johns Hopkins University

Brief Summary

This research is being done to examine epigenetic markers and mood changes across the menstrual cycle, particularly in premenstrual dysphoric disorder (PMDD). The investigators previously identified epigenetic biomarkers of postpartum depression, another reproductive affective disorder, and in this study aim to determine if these biomarkers also distinguish PMDD cases from healthy controls at different points in the menstrual cycle. By collecting biological samples (such as blood) and monitoring mood changes across the menstrual cycle, the investigators will be able to determine whether these epigenetic markers are associated with PMDD. The investigators plan to study these epigenetic markers during the follicular phase (roughly the first half of the menstrual cycle, from menses until ovulation) and the luteal phase (roughly the second half of the menstrual cycle, from ovulation to menses). The investigators will study this in two groups: 1) individuals who do NOT have premenstrual mood symptoms, and 2) individuals with premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD). The results will provide a comprehensive view of the changes in these systems across the menstrual cycle. This will add to the investigators understanding of the mechanisms that may cause PMS/PMDD.

Detailed Description

Premenstrual dysphoric disorder (PMDD) is a reproductive affective disorder with impairing mood symptoms that emerge monthly in the premenstrual (luteal) phase of the menstrual cycle. Reproductive affective disorders, including PMDD and postpartum depression, can be conceptualized as disorders of hormone sensitivity - an abnormal brain response to ovarian hormone fluctuations. Epigenetic variations in prior studies by the investigators were prospectively predictive of postpartum depression risk with over 80% accuracy. Recently, in a cross-sectional cohort of 50 women with and without PMDD, this postpartum depression epigenetic biomarker distinguished PMDD cases from controls in the luteal phase, suggesting this may indicate sensitivity to reproductive hormone change. The primary aim of this study is to explore whether this epigenetic biomarker is a broad marker for hormone sensitivity, by assessing women (controls, PMDD) in both the follicular and luteal phases of the participant's menstrual cycles, using a repeated measures approach. A secondary aim is to examine whether the epigenetic biomarkers differ between women with PMDD who have responded to selective serotonin reuptake inhibitor (SSRI) treatment versus those who have failed SSRIs. SSRIs are the first-line treatment for PMDD, yet many PMDD patients do not respond to SSRIs. This study will assess DNA methylation in a cohort of women with PMDD and controls. The investigators will compare the epigenetic biomarker between controls and PMDD in the follicular and luteal phases. Within the PMDD group, the investigators will compare the biomarker between those who have responded to SSRI treatment and those who have not. Blood will be collected at home by participants using a dried blood spot collection system.

Study Timeline

• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-13
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Study Start: 2025-07-01
• Primary Completion: 2030-02-15
• Study Completion: 2031-02-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 500

Inclusion Criteria

• female sex
• regular menstrual cycles (24-35 days)
• age 18-50 years
• ability to give written informed consent

Exclusion Criteria

• psychiatric medication use in the past 2 months;
• substance use disorder in the past 2 months (per MINI);
• lifetime history of psychotic disorder including schizophrenia, schizoaffective disorder, major depression with psychotic features (per MINI);
• history of psychiatric disorder other than PMDD in past year (per MINI);
• active suicidal ideation with plan or attempt in past 6 months (per MINI);
• steroid hormone or hormonal contraceptive use (except levonorgestrel as emergency contraceptive) in past 2 months;
• pregnancy in past 6 months;
• history of brain injury;
• current or history of endocrine disorder including uncontrolled diabetes or thyroid disease;
• BMI>40.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Presence of DNA Methylation Biomarkers (Comparing individuals with PMDD and controls)	From enrollment until study completion (approximately 3 months)	In the luteal phase, DNA methylation variations at HP1BP3, TTC9B will distinguish controls from individuals with PMDD. In the follicular phase, DNA methylation variations at HP1BP3 and TTC9B will not distinguish controls from PMDD. The investigators will be collecting dried blood spots and assaying these epigenetic markers using various DNA methylation techniques.

Secondary Outcome Measures

Name	Time	Method
Presence of DNA Methylation Biomarkers (comparing history of SSRI treatment vs SSRI non response)	From enrollment until study completion (approximately 3 months)	In the luteal phase, DNA methylation variations at HP1BP3, TTC9B will distinguish those with a history of SSRI treatment response versus SSRI non-response among women with PMDD. In the follicular phase, DNA methylation variations at HP1BP3, TTC9B will not distinguish those with a history of SSRI treatment response versus SSRI non-response among women with PMDD. Samples from which these assays are performed are from dried blood spots.
Epigenetic biomarkers associated with PMDD	From enrollment until study completion (approximately 3 months)	Novel epigenetic biomarkers associated with PMDD will be identified using dried blood spots and associated methods and techniques for analysis.

Trial Locations

Locations (1)

Johns Hopkins Reproductive Mental Health Center; 🇺🇸 Baltimore, Maryland, United States