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The Immunobiological Mechanisms of Depression in Perimenopause

Who can join

Ages 40 to 55 · Women · Healthy volunteers welcome

Inclusion Criteria:

* • Biological women, age 40 to 55.

  * Undergoing perimenopause according to STRAW criteria \[1\].
  * All races and national origins can be included.
  * English speaking (since all clinical rating scales to be used here have not been developed and validated for non-English speaking populations).
  * Able to give informed consent.
  * Able to comply with and complete study procedures.
  * Willing and able to take part of the different steps in the study, including follow-up research visit after 8 weeks and blood draws.

Exclusion Criteria:

* • Pregnant, nursing or transgender women (due to their hormonal status being different than what is investigated in this project).

  * Incarcerated individuals.
  * Subjects with dementia or otherwise cognitively impaired subjects with difficulty understanding the study procedures.
  * Patients with an active somatic disorder primarily involving the immune system (autoimmune diseases such as Crohn's disease, multiple sclerosis, or rheumatoid arthritis; or hematological diseases such as lymphoma or leukemia or HIV). Research staff will consult with the PIs in cases of uncertainty.
  * Patients with untreated hormonal conditions affecting the reproductive system.
  * Patients on chronic and systemic immunomodulatory treatment. Examples are patients with a liver or kidney transplant and medications used for disorders involving the immune system, as mentioned above. Examples of immunomodulatory treatments are cyclosporin, azathioprine, infliximab and chronic corticosteroid treatment.
  * Women already taking hormonal substitution before the research visit (either for perimenopause or/and as contraceptive) or replacement will be excluded,
  * Patients taking lithium, neuroleptic- or mood stabilizing medications (antidepressants, such as SSRIs and SNRIs, are allowed).
  * Patients undergoing active treatment for any form of cancer (chemotherapy or immunomodulatory treatments).

About the study

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.

Sponsor: Van Andel Research Institute · Participants: 120 · Started: Mar 13, 2025

Contact the study team

• Lena Cecilia Brundin, MD, PhD · Phone: 616-234-5379
• Qiong Sha, PhD · Phone: 616-234-5498

Official record on ClinicalTrials.gov — NCT07910552

Locations in the U.S.

Conditions

• Depression

From ClinicalTrials.gov, data retrieved Nov 15, 2026. Each study sets its own eligibility; the study team decides who can join.