Identification and Validation of Epigenetic Biomarkers of PMDD

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.

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.