Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional) | RFA MH 21 106

Opportunity Information: Apply for RFA MH 21 106

Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional) is an NIH discretionary grant opportunity (Funding Opportunity Number RFA-MH-21-106) that supports exploratory, early-stage translational research on why mood and psychosis symptoms can first appear, worsen, or change during the menopause transition (MT). The central goal is to generate mechanistic, hypothesis-driven evidence that clarifies what is happening in the brain and body during MT that may increase vulnerability to psychiatric symptoms, and to use that knowledge to point toward future treatment targets and intervention strategies. The R21 mechanism signals that the program is interested in innovative, higher-risk projects that can open new lines of investigation rather than large, long-term definitive trials. Clinical trials are allowed but not required, which gives applicants flexibility to propose human laboratory studies, biomarker-focused clinical work, observational cohorts with mechanistic measures, or small proof-of-concept intervention studies when justified.

The scientific scope centers on mood and psychotic disorders and related symptom dimensions during MT, explicitly including perimenopausal depression (PMD), generalized anxiety disorder, bipolar disorder, and schizophrenia, along with associated mood lability, anxiety, sleep disruption, and psychosis-spectrum experiences that may fluctuate with hormonal and physiological changes. A major emphasis is on translational approaches that connect clinical phenomena to underlying neurobiological and behavioral mechanisms. This includes work that investigates how changes in reproductive steroids and related endocrine dynamics during MT may shape mood regulation, stress responsivity, reward processing, cognition, and perception. Projects can also focus on how steroid fluctuations interact with neurotransmitter systems, neural circuits, inflammation, circadian rhythms, and sleep architecture, especially when these relationships can be measured with modern tools such as neuroimaging, electrophysiology, digital phenotyping, endocrine sampling strategies, or other biomarker approaches.

The FOA highlights several specific areas of interest. One is the combined presentation of classic depressive symptoms with common menopause-related symptoms such as hot flashes, night sweats, and sleep disturbance, acknowledging that these experiences can cluster together and may share mechanisms or mutually reinforce one another. Another is improving diagnostic precision by examining how mood and psychosis symptoms vary by menopausal stage, and how best to distinguish new-onset or stage-linked psychiatric symptoms from pre-existing disorders, recurrence, medication effects, medical comorbidities, or other differential diagnoses relevant to midlife. The announcement also encourages careful study of co-occurring psychiatric symptoms and menopause symptoms, including how symptom profiles evolve over time and whether certain symptom constellations represent distinct subtypes with different mechanistic drivers and treatment implications.

In addition to biological mechanisms, the opportunity recognizes that midlife often comes with psychosocial exposures that can meaningfully affect psychiatric risk and symptom expression, such as caregiving stress, occupational strain, changing family roles, relationship changes, trauma history, and socioeconomic pressures. Competitive applications are expected to take these factors seriously, either by incorporating them into study design and analytic plans or by showing how the proposed mechanistic model accounts for them. The overarching expectation is that applications will be comprehensive in their mechanistic framing and will clearly explain how the proposed methods test well-justified hypotheses about mechanisms of action underlying mood and psychosis symptoms during MT.

Applications will be reviewed with strong attention to the depth and coherence of the mechanistic rationale, the quality of the hypothesis-driven approach, and how well the project links menopause transition biology and behavior to clinically meaningful mood or psychosis outcomes. Interdisciplinary collaboration is explicitly encouraged, reflecting the complexity of MT-related psychiatric risk and the need for teams that can integrate psychiatry, neuroscience, endocrinology, gynecology, sleep medicine, and behavioral science.

Eligibility is broad and includes many organization types beyond traditional research universities. Eligible applicants include federal, state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; public housing authorities/Indian housing authorities; and Native American tribal governments and tribal organizations. The FOA also specifically calls out additional eligible groups such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, U.S. territories or possessions, regional organizations, and non-U.S. entities (foreign organizations). The sponsoring agency is the National Institutes of Health, the activity category is Health, and the CFDA numbers listed are 93.242 and 93.313. The opportunity originally closed on February 9, 2021, with a creation date of November 18, 2020.

• 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, 93.313.
• This funding opportunity was created on 2020-11-18.
• Applicants must submit their applications by 2021-02-09. (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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