An observational study in Perimenopause and Major Depressive Episode (MDE), sponsored by Van Andel Research Institute. Recruiting at 4 sites in United States. Open to female participants aged 40 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Van Andel Research Institute · Observational
This project aims to identify immunobiological mechanisms underlying the development of depression during the perimenopause. During the perimenopause, the risk for recurrence of depression is increased 13-fold among women who previously had depression. Moreover, perimenopause overlaps with the age span exhibiting the highest suicide rate for women. The perimenopause can last for several years and starts when estrogen and progesterone levels begin to fluctuate, gradually declining. Sex hormones are powerful modulators of the immune response and the investigators therefore propose that changes in lymphocytes play a central role in depression during this time. Notably, our previous work has demonstrated deficient regulatory T-cell responses in women with post- partum depression and identified a specific pro-inflammatory profile that predicts depression during pregnancy. Importantly, our new pilot data derived from women with severe depression in the perimenopausal age span reveals alterations in tryptophan metabolites that control T- cell responses as well as in the methylation of genes involved in T-cell fate and chromatin remodeling. Taken together, these data support the hypothesis that the perimenopausal hormonal shifts induce a pro-inflammatory state, regulated by chromatin modifications in T-cells, that triggers depression in vulnerable women.
To test this hypothesis, the investigators will enroll 180 perimenopausal women aged 40-55, approximately half with depression and half without a diagnosis of depression. All participants will complete psychiatric assessments and provide blood samples to measure sex hormones, inflammation and immune cell changes. Women with depression will be reassessed approximately eight weeks later to identify blood markers that change as depressive symptoms improve.
This project seeks to improve understanding of the biological mechanisms of depression during perimenopause and aid the development of predictive biomarkers and more effective treatments.
Perimenopause constitutes a high-risk period for developing depressive symptoms and recurrence of depression. Although hormonal changes are considered to trigger symptom development, little is known about the underlying biological mechanisms or why some women are at increased risk. Since both estrogen and progesterone induce changes in the immune response, this project focuses on the immunobiological mechanisms underlying depression in perimenopause.
The investigators' working hypothesis is that perimenopausal hormonal shifts induce a pro-inflammatory state, modulated by intrinsic chromatin properties in lymphocytes, that contributes to depression. The investigators propose that the risk of developing perimenopausal depression depends on levels of aryl hydrocarbon receptor (AhR)-binding ligands in plasma, the chromatin landscape of immune cells affected by these ligands, and sex hormone levels that act in concert with the ligands to sustain a pro-inflammatory state.
Aims:
To test these hypotheses, the investigators will enroll 180 perimenopausal women aged 40-55 years at Weill Cornell Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, and Pine Rest Christian Mental Health Services. Approximately 90 women will have depression, and 90 will have no or mild depressive symptoms without a diagnosis of depression. Perimenopausal status will be established using the Stages of Reproductive Aging Workshop criteria. A structured diagnostic interview using DSM-5 criteria will confirm or rule out a diagnosis of depression.
Participants will undergo clinical assessments and blood sampling. The Hamilton Depression Rating Scale will be the primary measure of depression severity. Additional assessments will measure menopausal symptoms, anxiety, trauma history, suicidal thoughts and behaviors, and functioning. Blood samples will be collected between 7:00 and 10:00 AM.
For Aim 1, the investigators will quantify plasma tryptophan metabolites, inflammatory cytokines and sex hormones. The working hypothesis is that women with depression in perimenopause have reduced levels of immunoregulatory tryptophan metabolites, worsening peripheral inflammation. Biomarker levels will be compared between groups and examined in relation to depression severity and sex hormone levels.
For Aim 2, peripheral immune cell populations will be characterized using flow cytometry. ATAC sequencing, Illumina EPIC arrays and RNA sequencing will assess chromatin accessibility, DNA methylation and gene expression in sorted naïve T-cells. The investigators expect to detect differences in transcriptional regulation, reflected in distinct inflammatory responses in women with depression in perimenopause.
For Aim 3, the approximately 90 women with depression will be reassessed eight weeks after the first visit, with repeat clinical assessments and blood sampling. This observational follow-up will include women starting hormone therapy as part of their clinical care and women who do not. The working hypothesis is that women receiving hormone therapy will show reduced pro-inflammatory cytokines and increased regulatory T-cells, along with improvement of depressive symptoms.
The findings may aid the identification of women at risk and the development of more effective treatments. The investigators predict that these distinct inflammatory responses will be linked to the development of depression. The investigators also expect improvement of depressive symptoms and reversal of immunobiological markers in women receiving hormonal therapy. The investigators envision that the project will lead to an improved understanding of the molecular underpinnings of depression during perimenopause, aiding the future identification of biomarkers of women at risk as well as the development of more effective treatments.
8,577 studies on the registry are indexed under Depression; 1,720 are open to participants now.
This study's planned enrollment of 120 is below the median of 175 across 1,257 observational studies indexed under Depression.
Browse Depression studies →Van Andel Research Institute is the lead sponsor of 4 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Women between 40-55 years of age will be approached in the screening. Our recruiters will discuss the study in a private room with potential study participants, to first check whether the approached women meet the STRAW criteria for perimenopause (≥ 7-day persistent; recurrence within 10 cycles) variability in their menstrual cycle), before scheduling consent.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Biological women, age 40 to 55.
Exclusion Criteria:
Pregnant, nursing or transgender women (due to their hormonal status being different than what is investigated in this project).
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Control perimenopause women without depression
Inflammatory markers
IL-1-33 and acute phase reactants ICAM, VCAM, CRP, SAA) will be measured using high-sensitivity ELISAs, Mesoscale platform or Luminex platforms
Time frame: Inflammatory markers will be measured at baseline and the follow up time point: 8 weeks after the first visit for the depressed group.
thyroid status, hormonal status
Measure estrogen, progesterone, luteinizing hormone and follicle stimulating hormone, cortisol levels for controlling their interactions with cytokines and AhR ligands.
Time frame: At the baseline and follow up visit (8 weeks)
glucose levels
For controlling interactions with hormones and cytokines, AhR ligands.
Time frame: At the baseline and follow up visit (8 weeks)
hemoglobin levels
For controlling interactions with hormones and cytokines, AhR ligands.
Time frame: At the baseline and follow up visit (8 weeks)
RNA sequencing
Assess gene expression levels
Time frame: At baseline
methylation analysis
Assess genome-wide methylation levels
Time frame: At baseline
ATAC sequencing
ATAC sequencing on the naïve T-cells to assess chromatin accessibility.
Time frame: At baseline
FACS profiling
sorting and staining of lymphocytes to identify immune cell profile changes
Time frame: until the end of the study
Not enrolling at this site.
Plan to share: Undecided
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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