Identification and Validation of Epigenetic Biomarkers of PMDD (BIO)

May 6, 2026 updated by: Johns Hopkins University
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.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Victoria Seo, B.S.
  • Phone Number: 302-464-8320‬
  • Email: vseo1@jh.edu

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins Reproductive Mental Health Center
        • Contact:
        • Principal Investigator:
          • Liisa Hantsoo, Ph.D.
        • Contact:
          • Victoria Seo, B.S.
          • Phone Number: 302-464-8320‬
          • Email: vseo1@jh.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from Virginia, Washington DC, and Maryland (Baltimore area).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Control
Eligible participants that pass inclusion and exclusion criteria who do not have premenstrual mood symptoms.
Premenstrual Dysphoric Disorder (PMDD)
Eligible participants that pass inclusion and exclusion criteria who do have premenstrual mood symptoms. Symptoms must be severe enough to meet PMDD criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of DNA Methylation Biomarkers (Comparing individuals with PMDD and controls)
Time Frame: 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.
From enrollment until study completion (approximately 3 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epigenetic biomarkers associated with PMDD
Time Frame: 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.
From enrollment until study completion (approximately 3 months)
Presence of DNA Methylation Biomarkers (comparing history of SSRI treatment vs SSRI non response)
Time Frame: 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.
From enrollment until study completion (approximately 3 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Liisa Hantsoo, Ph.D., Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2025

Primary Completion (Estimated)

February 15, 2030

Study Completion (Estimated)

February 15, 2031

Study Registration Dates

First Submitted

January 8, 2025

First Submitted That Met QC Criteria

January 8, 2025

First Posted (Actual)

January 13, 2025

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00484410
  • 1R01MH135896 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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