Description

This NIH funding opportunity (R21 mechanism) encourages exploratory and developmental research focused on the cellular and molecular biology underlying complex brain disorders such as schizophrenia, bipolar disorder, major depression, anxiety disorders, tic disorders, and autism. The emphasis is on understanding the biology of high confidence risk factors—genetic, environmental, or multifactorial—that contribute to these disorders, particularly at the intracellular, transcellular, and neural circuit levels.

Applicants may propose hypothesis-generating or hypothesis-testing studies using in vivo, in situ, or in vitro experimental paradigms, including model organisms or human cell-based assays. Behavioral studies are optional but not required. Importantly, the research should not attempt to model the disorders themselves but rather aim to elucidate the neurobiological impact of individual or combined risk factors, including their molecular and cellular components and their roles within defined biological processes.

The FOA encourages the use of novel technologies (e.g., CRISPR/Cas9 gene editing, BRAIN Initiative tools) and resources such as genetically modified organism repositories and human cell lines from the NIMH Repository and Genomics Resource. Data and biological processes generated should be shared in detail to enrich common or federated data resources (e.g., Gene Ontology, Synaptic Gene Ontology, FAIR Data Informatics) to bridge gaps between disease risk factors, biological mechanisms, and therapeutic target identification.

Non-responsive topics include research focused on disease modeling, candidate risk genes or environmental factors without strong statistical support, primary phenotyping of human subjects or clinical populations (except for cell/tissue-based assays), and sole focus on behavioral paradigms, pharmacology, drug discovery, or immunological challenges.