The SPARK-PMDD Study

Studying Psychological Changes And inflammatoRy marKers in 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.

Inclusion Criteria:

Participants must:

• Have been assigned female sex at birth (AFAB), with ovaries
• Be aged between 18-42 years (inclusive)
• Be able to provide written informed consent
• Be premenopausal
• Have regular menstrual cycles (24-35 days; 5-8 menstrual cycles within the previous 6 months)
• Have a body mass index (BMI) between 18 and 30 kg/m².
• Have access to a computer, tablet or smartphone with an internet connection.
• Be registered with a UK General Practitioner (GP) and consent to the study team contacting their GP if clinically indicated.

PMDD group only - Participants must additionally:

• Meet DSM-5 diagnostic criteria for Premenstrual Dysphoric Disorder (PMDD), confirmed through prospective symptom ratings and the study diagnostic assessment.

Healthy control group only - Participants must additionally:

• Have no current or previous diagnosis of PMDD.
• Report no clinically significant premenstrual symptoms on prospective symptom ratings.
• Have no lifetime psychiatric illness
• Meet all other study eligibility criteria.

Exclusion Criteria:

Participants will be excluded if they:

• Have a lifetime history of a psychotic disorder (including schizophrenia, schizoaffective disorder or major depressive disorder with psychotic features) or bipolar disorder (past or present)
• Meet criteria for any other current major psychiatric disorder that would interfere with study participation, as determined by the MINI International Neuropsychiatric Interview.
• Have a history of drug or alcohol dependence within the previous 12 months.
• Have a diagnosed intellectual disability, pervasive developmental disorder or significant neurological disorder (e.g. Alzheimer's disease, epilepsy or Parkinson's disease).
• Are currently pregnant or breastfeeding, or are planning pregnancy during the study period.
• Have an acute infection, autoimmune disorder, or regularly use anti-inflammatory or antibiotic medication that could influence immune biomarkers.
• Have a current or previous gynaecological condition (e.g. endometriosis or polycystic ovary syndrome) or have undergone gynaecological surgery within the previous 12 months.
• Have used hormonal contraception or other steroid hormone treatment within the previous 6 months (except emergency levonorgestrel contraception or temporary hormone treatment for oocyte cryopreservation that has not affected menstrual cycle regularity).
• Have a significant medical condition that may affect study outcomes (e.g. cancer, inflammatory disease, liver disease, kidney disease or Crohn's disease).
• Are currently participating in a Clinical Trial of an Investigational Medicinal Product (CTIMP). Eligibility following recent participation in a CTIMP will be considered on a case-by-case basis.
• Are assessed as presenting an immediate or high risk of suicide requiring urgent clinical intervention. Suicidal ideation alone is not an exclusion criterion because it is recognised as a feature of PMDD; however, participants identified as being at significant risk will be excluded and referred to appropriate clinical services.