Transformative CNS Drug Discovery

This section introduces a transdiagnostic, Research Domain Criteria (RDoC)-based drug discovery framework for the effective use of translational technologies such as those described in the previous section. The RDoC framework was introduced in 2009, but there are actually few published RDoC-based drug discovery studies, perhaps because researchers find it challenging to conceptualize and design these. Therefore, this section aims to provide drug discovers with insights, concepts, and examples to build a basis for designing their own studies. First, by explaining the application of the RDoC concept to translational drug development, A Paradigm Shift from DSM-5 to RDoC: Application to Translational CNS Drug Development, including examples from the NIMHs “fast-fail” experimental medicine approach. Second, by providing insight on how environmental factors are approached from an RDoC-perspective and explaining the role of the exposome—that is, the totality of exposures from conception onward—in the pathoetiology and course of mental disorders. Third, by giving examples of successful clinical applications, such as noninvasive brain stimulation (NIBS) to treat circuitry phenotypes in transdiagnostic, precision medicine approaches. We hope that drug discoverers will find the chapters in the Transformative CNS Drug Discovery section informative and helpful in their quest for novel neurotherapeutics.