Clinical trial NCT06771583: Identification and Validation of Epigenetic Biomarkers of PMDD
Official title: Identification and Validation of Epigenetic Biomarkers of PMDD
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: PMDD
Premenstrual Dysphoric Disorder (PMDD)
Premenstrual Syndrome-PMS
Premenstrual Syndrome
Menstrual Cycle
Keywords: menstrual cycle
pms
luteal phase
womens health
reproductive health
reproductive mental health
epigenetics
dna methylation
premenstrual
pmdd
women
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2025-01-13
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited from Virginia, Washington DC, and Maryland (Baltimore area).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Presence of DNA Methylation Biomarkers (Comparing individuals with PMDD and controls)
timeFrame: From enrollment until study completion (approximately 3 months)
Secondary outcomes:
measure: Presence of DNA Methylation Biomarkers (comparing history of SSRI treatment vs SSRI non response)
timeFrame: From enrollment until study completion (approximately 3 months)
measure: Epigenetic biomarkers associated with PMDD
timeFrame: From enrollment until study completion (approximately 3 months)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Reproductive Mental Health Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Liisa Hantsoo, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: