Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional) | PAR 25 282

Opportunity Information: Apply for PAR 25 282

The National Institutes of Health (NIH) funding opportunity "Mood and Psychosis Symptoms during the Menopause Transition (R21 Clinical Trial Optional)" (PAR-25-282) supports early-stage, exploratory translational research aimed at clarifying why mood and psychotic symptoms can first appear, worsen, or change in character during the menopause transition. The central goal is to generate mechanistic insight that can point to concrete biological and behavioral targets for future intervention development, with particular attention to conditions such as perimenopausal depression, generalized anxiety disorder, bipolar disorder, and schizophrenia, as well as clinically meaningful subthreshold symptom patterns. The NOFO emphasizes innovative, hypothesis-driven projects that connect clinical phenomena observed in midlife individuals to underlying neurobiology and behavior, rather than purely descriptive studies.

A major focus is understanding how the menopause transition intersects with psychiatric symptoms in real-world clinical presentations. This includes studying "classic" depressive symptoms alongside hallmark menopause-related symptoms such as hot flashes, night sweats, and sleep disturbance, and examining how these symptom clusters interact to influence distress, impairment, and diagnostic clarity. The opportunity highlights the importance of parsing overlap and misattribution (for example, sleep disruption from vasomotor symptoms versus sleep changes associated with depression or mania), and encourages careful attention to differential diagnosis and staging. Projects that improve the ability to identify or characterize mood and psychosis symptoms by menopausal stage, or that clarify how symptom profiles shift across the transition, align well with the stated priorities.

Another key area of interest is the role of reproductive steroids and related physiological changes in regulating mood, cognition, perception, and behavior during the menopause transition. Applicants are encouraged to examine how fluctuations or declines in hormones and downstream signaling pathways might alter stress responsivity, neural circuitry, neurotransmission, inflammation, sleep-wake regulation, or other systems plausibly linked to depression, anxiety, bipolar symptoms, and psychosis-related experiences. The translational framing suggests NIH is looking for studies that can bridge levels of analysis, such as linking endocrine measures to neural or behavioral readouts, identifying candidate mechanisms of action, or isolating modifiable pathways that could later be targeted by pharmacologic, behavioral, device-based, or combined interventions.

The NOFO also explicitly encourages research that captures the complexity of midlife context. This includes investigating co-occurring psychiatric and menopause symptoms and incorporating psychosocial factors that commonly intensify during midlife, such as caregiving stress, occupational strain, relationship changes, health comorbidities, and accumulated adversity. The intent is not to treat psychosocial variables as background noise, but to integrate them into explanatory models where relevant, especially when they interact with biological changes to shape symptom risk, onset, recurrence, or severity. Interdisciplinary collaboration is strongly encouraged, reflecting the expectation that meaningful progress will often require teams spanning psychiatry, neuroscience, endocrinology, gynecology, sleep research, epidemiology, psychology, and related disciplines.

This is an R21 mechanism, which generally supports exploratory and developmental work, making it well-suited to piloting innovative approaches, testing novel mechanistic hypotheses, establishing feasibility, or generating preliminary data that can justify larger subsequent trials or longitudinal studies. Clinical trials are optional, meaning applicants may propose mechanistic clinical studies with or without an intervention component, as long as the work remains aligned with translational, mechanism-focused aims. Review is expected to prioritize the strength and clarity of the hypothesis-driven approach and the depth and coherence of the proposed neurobiological and mechanistic framework explaining mood and psychosis symptoms during the menopause transition.

Eligibility is broad and includes many organization types: state, county, city, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other eligible entities. The announcement also calls out additional eligible applicants such as Historically Black Colleges and Universities, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions, faith-based or community-based organizations, regional organizations, non-U.S. (foreign) entities, and U.S. territories or possessions. The opportunity is categorized as a discretionary NIH grant in the health area, associated with CFDA numbers 93.242 and 93.313, with an original closing date listed as January 7, 2028, and a creation date of November 22, 2024.

• 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 2024-11-22.
• Applicants must submit their applications by 2028-01-07.
• 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.

Apply for PAR 25 282

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