Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional) | PAR 22 036

Opportunity Information: Apply for PAR 22 036

Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional) is an NIH discretionary grant opportunity (PAR 22 036; CFDA 93.242) that supports early-stage, exploratory translational research focused on why mood and psychosis symptoms can emerge for the first time, worsen, or become harder to treat during the menopause transition. The opportunity is a reissue of RFA-MH-21-106 and is centered on building a clearer, mechanism-based understanding of perimenopausal depression, anxiety (including generalized anxiety disorder), bipolar disorder, schizophrenia, and related symptom profiles as ovarian function changes across perimenopause and into menopause. The broader goal is practical: identify biological, behavioral, and psychosocial targets that could later be used to develop or refine interventions, including novel treatments or better ways to match existing treatments to the right patients at the right menopausal stage.

A major emphasis is on innovative, hypothesis-driven studies that connect observable symptoms to underlying mechanisms. Applicants are encouraged to look beyond “depression during midlife” as a single category and instead examine how classic psychiatric symptoms interact with menopause-related features such as hot flashes, night sweats, and sleep disruption, as well as the psychological and functional challenges that often cluster in this period (for example, distress related to bodily changes, cognitive complaints, or shifting family and work roles). The FOA highlights reproductive steroids as a key line of inquiry, inviting research on how changes in hormones and hormone sensitivity may influence brain systems that regulate mood, threat processing, reward, sleep, cognition, and perception. Projects can also focus on careful characterization and diagnosis of mood and psychosis symptoms by menopausal stage, which matters because symptom patterns and risk may differ across early vs late transition, and because some presentations may be misattributed either to menopause alone or to primary psychiatric illness without considering the hormonal context.

The scope also includes studying co-occurrence and differential diagnosis. This means the FOA is interested in work that disentangles overlapping symptom drivers, such as when insomnia is caused primarily by vasomotor symptoms versus when it reflects an evolving mood episode, or when anxiety and irritability are part of a hormonal transition versus an anxiety disorder requiring specific treatment. Similarly, for psychosis-spectrum symptoms, the FOA supports research that can clarify when new or worsening symptoms relate to menopausal-stage biology, medication changes, sleep loss, stress exposure, or other midlife factors. Psychosocial conditions common in midlife are explicitly called out as important context, encouraging researchers to incorporate real-world stressors and protective factors (caregiving burden, relationship transitions, workplace strain, trauma exposure, health comorbidities, socioeconomic pressures) into mechanistic models rather than treating them as mere background variables.

Because this is an R21 mechanism, the intent is to fund novel, high-impact exploratory projects that can generate preliminary mechanistic evidence, new biomarkers, experimental paradigms, or proof-of-concept findings that justify larger follow-on studies. The “Clinical Trial Optional” designation indicates that applicants may propose either clinical trial work or non-trial studies, depending on what best tests the scientific question. Reviewers are expected to prioritize the strength and clarity of the mechanistic rationale, the translational potential, and how comprehensively the proposed approach addresses neurobiology and mechanisms of action underlying mood and psychosis symptoms during the menopause transition.

Eligibility is broad and includes many organization types: state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; public and state-controlled universities; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations other than small businesses; and small businesses. The FOA also explicitly welcomes applications from a range of institutions and entities that often serve specific communities or regions, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, U.S. territories or possessions, and even non-U.S. (foreign) organizations and regional organizations. The sponsoring agency is the National Institutes of Health, and the listing indicates an original closing date of 2023-01-13, reflecting the posted cycle information for this opportunity.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2021-09-20.
• Applicants must submit their applications by 2023-01-13. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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