Premenstrual Dysphoric Disorder (PMDD)

Scientists have found that the immune system, the body's system dedicated to fighting infections, can be in a state of "hyperactivity" (i.e., more active than you would normally expect) in some people with depression and postnatal depression, despite the lack of any actual ongoing infection. This response is referred to as inflammation. This discovery has unveiled unique opportunities to identify new medications to help patients with this heightened inflammation who have also not been responding to their antidepressant medications. This study aims to explore how inflammation in the body may be linked to symptoms of Premenstrual Dysphoric Disorder (PMDD) across the menstrual cycle, and how thoughts, emotions, and behaviours also may change throughout the cycle. We are recruiting two groups of people: People with a clinical or provisional (suspected) diagnosis of PMDD, and healthy controls who experience mild/no premenstrual changes. Over a two-month period, participants will complete daily psychological assessments across two menstrual cycles and will come into King's College Hospital (KCH) twice during one menstrual cycle to provide blood samples to measure their inflammation. By comparing these groups, we hope to gain a better understanding of the biological and psychological factors involved in PMDD, with the long-term goal of improving treatment options.

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.

Premenstrual dysphoric disorder (PMDD) is a severe affective disorder impacting millions of women worldwide, thought to be due to altered sensitivity to hormone fluctuations across the menstrual cycle. Neuroactive steroid hormones (NAS) and the gamma-aminobutyric acid (GABA)-A receptor (GABAAR) are thought to play a role in PMDD. This research will assess the blood levels of GABAergic NAS, expression of associated enzymes, and expression of GABAAR subunits across the premenstrual (luteal) phase of the menstrual cycle in healthy controls and individuals with PMDD. Within the PMDD group, the investigators will assess how these measures are affected by a low-dose antidepressant medication versus placebo. The results will provide a comprehensive view of the changes in these systems across the menstrual cycle and will add to the investigator's understanding of the mechanisms that underlie PMDD, as well as therapeutic mechanisms of PMDD treatment.