The SPARK-PMDD Study

N/ANot Yet RecruitingNCT07771426

King's College London120 enrolled

Overview

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.

Premenstrual dysphoric disorder (PMDD) is a reproductive mood disorder characterised by impairing emotional, cognitive, and physical symptoms that emerge during the premenstrual (luteal) phase of the menstrual cycle and remit shortly after menstruation begins. PMDD may reflect heightened sensitivity to normal fluctuations in ovarian hormones, with emerging evidence suggesting that interactions between sex hormones, inflammation, and psychological processes may contribute to symptom emergence. Recent prospective research has found that inflammatory markers, including CXCL8 and TNFα, are elevated during the luteal phase and that CXCL8 is associated with PMDD symptom severity. Psychological research has also identified cyclical changes in emotional reactivity, distress tolerance, rumination, and related processes among individuals with PMDD, suggesting that these may represent important and potentially modifiable treatment targets. The primary aims of this study are to investigate whether inflammatory markers differ between individuals with PMDD and healthy controls across the follicular and luteal phases of the menstrual cycle, and to determine whether inflammatory markers are associated with PMDD symptom severity. The secondary aims are to examine whether key emotional and cognitive variables differ across menstrual cycle phases between individuals with PMDD and healthy controls, and to determine whether the magnitude of these psychological changes is associated with PMDD symptom severity. The study will use a repeated-measures design, with participants assessed during both the follicular and luteal phases of the menstrual cycle. Exploratory aims are to examine daily fluctuations in psychological outcomes across two consecutive menstrual cycles and, in a subgroup of 20 participants, to explore the lived experience of PMDD, attitudes towards current biological and psychological treatments, and perspectives on potential novel treatment targets.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 42 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Inflammatory Biomarkers (Comparing individuals with PMDD and controls)

The investigators will be collecting peripheral blood samples and assaying inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory and anti-inflammatory cytokines, including interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α.