Drug Discovery and Development Initiatives at the National Institute of Mental Health: From Cell-Based Systems to Proof of Concept

Publisher Summary

The mission of the National Institute of Mental Health (NIMH) is to reduce the burden of mental illness and behavioral disorders through research. Toward this goal, the NIMH promotes the development of novel models as an integral part of a larger effort aimed at understanding the neurobiological mechanisms responsible for both normal and disrupted cognitive and emotional control and toward the development of new mechanism of action therapeutics. This chapter presents an overview of NIMH efforts to stimulate treatment discovery and development through support of basic research, targeted drug discovery programs, translational research support, and facilitation of communication between public, private, and government agencies. The NIMH encourages the development and refinement of preclinical models through investigator-initiated research support and by targeted efforts addressing the need for novel mechanism of action treatments. The potential for success in developing new models that reliably predict clinical efficacy or adverse effects relies ultimately on improvements in both clinical evaluation and the application of basic science toward translational boundaries. Communication between clinicians and clinical and basic neuroscientists is essential for this synthesis. Support for basic science is critical for understanding the underlying biological mechanisms and functional significance of newly identified clinical indicators of risk, pathology, or treatment response. As pathways are identified and linked, new molecular and cellular targets for treatment development are likely to emerge from this translational discovery science. These discoveries need to be adapted into cellular, circuit-based, physiological, and/or behavioral models to allow screening and efficacy testing of candidate therapeutic compounds.