This Funding Opportunity Announcement (FOA) seeks research grant applications designed to develop innovative ways of understanding mental disorders in clinical studies on the basis of experimental research criteria rather than traditional diagnostic categories. This FOA stems from the NIMH Research Domain Criteria (RDoC) project that is intended to further a long-range goal of contributing to diagnostic systems as informed by research on genetics, neuroscience, and behavior.The purpose of this FOA is to encourage applications to study mechanisms that may cut across multiple traditional diagnostic categories. Applications submitted in response to this FOA should be based upon RDoC criteria (see http://www.nimh.nih.gov/research-funding/rdoc.shtml for the RDoC criteria developed to date).Five organizing domains have been identified in the draft specification.These include Negative Valence Systems (i.e., aversive motivational dimensions), Positive Valence Systems, Cognitive Systems, Social Process Systems, and Arousal/Regulatory Systems. Consensus workshops and guidance documents on Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Working Memory (subsidiary of Cognitive Systems), and Social Processes, have been completed, and applications must focus on at least one of the constructs that have been defined in these RDoC workshops, as indicated in the workshop proceedings.Interested applicants are encouraged to consult the NIMH RDoC web site (http://www.nimh.nih.gov/research-funding/rdoc.shtml) for current information regarding these constructs.