The funding opportunity "Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed)" is offered by the National Institute of Mental Health (NIMH) to support exploratory and developmental research focused on the biological mechanisms underlying complex brain disorders. This opportunity targets high-risk, early-stage research with limited or no preliminary data. Studies should aim to elucidate intracellular, transcellular, and circuit-level neural functions influenced by genetic and environmental risk factors associated with disorders such as schizophrenia, bipolar disorder, autism, and major depression. The focus is not on modeling disorders but on understanding the neurobiological impacts of specific risk factors.

Research areas include, but are not limited to, gene function analysis, environmental risk factor mechanisms, developmental influences, and advanced cell-based experimental systems like induced pluripotent stem cells. The initiative encourages leveraging novel tools and methodologies, such as those developed through the BRAIN Initiative, and emphasizes rigorous experimental design and data dissemination to federated resources like Gene Ontology. The program does not support studies centered on behavioral models, drug discovery, or immunological paradigms.

The grant provides funding for up to two years, with a total direct cost limit of $275,000 and no more than $200,000 allocated to a single year. Eligible applicants include higher education institutions, nonprofits, for-profit organizations, government entities, and foreign organizations. Applications must strictly follow NIH guidance for electronic submission through systems like ASSIST or Grants.gov and ensure compliance with NIH's data management and sharing policies.

Deadlines for applications occur three times a year on February 16, June 16, and October 16, beginning in 2025, and the program will remain open until September 8, 2026. Review criteria emphasize significance, innovation, scientific rigor, feasibility, investigator expertise, and resource availability. Research must focus on topics supported by robust genetic or epidemiological data and must incorporate experimental controls to ensure reliability and reproducibility.

Applicants are encouraged to consult NIMH staff during the project planning phase to align proposals with program goals. Proposals must include a clear resource-sharing plan and budget for data submission to platforms like the NIMH Data Archive. For further assistance, applicants can contact designated NIMH scientific, administrative, and technical support staff. Successful applications will align with NIMH’s strategic priorities and demonstrate potential to advance fundamental understanding of brain disorders.