Federal Grant Award Summary

Northwestern University's Sponsored Research Division received a $781,358 Project Grant from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242), effective April 1, 2026 through December 31, 2030. The award funds research to determine the mechanisms and therapeutic potential of novel cholinergic antipsychotics for treating schizophrenia. The project will employ in vivo imaging, microdialysis, and behavioral testing methodologies to investigate how emerging cholinergic receptor agonists—specifically xanomeline and the M4 receptor selective modulator VU0467154—compare to traditional dopamine D2 receptor (D2R)-targeting antipsychotics. Building on preliminary findings suggesting that clinical antipsychotic efficacy correlates more strongly with normalization of dopamine D1 receptor-expressing striatal neurons than D2 receptors, the research will explore the mechanistic overlap between traditional and novel drug classes and evaluate their potential to address treatment-resistant symptoms and adverse effects in patients unresponsive to conventional therapies.

The grant supports fundamental neuroscience research designed to advance understanding of psychiatric treatment mechanisms and inform the development of more effective antipsychotic medications. Deliverables will include scientific publications, mechanistic data on drug efficacy pathways, and behavioral validation models compatible with neurophysiological recording techniques. This research addresses a critical gap in mental health treatment, as approximately 30% of schizophrenia patients do not respond adequately to traditional antipsychotics, and these drugs frequently fail to address cognitive and negative symptoms while producing substantial adverse effects.