5 Although both MATRICS and CNTRICS focused on one clinical concern (cognition in schizophrenia), their rigorous focus and collaborative process—distilling a large and nuanced literature to a manageable number of welldefined domains, followed by standardization of measurement—provided a template for the processes

by which RDoC has advanced. In a parallel but more comprehensive initiative, RDoC aims to define major domains for the study of mental illness and validate them using optimal genetic, neuroscientific, physiological, behavioral, and self-report measures. The RDoC matrix The RDoC scheme can be represented as a two-dimensional Inhibitors,research,lifescience,medical matrix (Table I). The rows represent the “dimensions

of observable behavior and neuroblological measures” specified in Goal 1.4 of the NIMH Strategic Plan. These dimensions are referred to as Inhibitors,research,lifescience,medical “constructs” to represent their status as concepts regarding brain organization and functioning that evolve with advances in research. In turn, constructs are grouped under five superordinate domains of activity, which reflect a conceptual typology of functions as well as empirical relationships among activity in related brain circuits. Table I. Research Domain Criteria Matrix. “Circuits” Inhibitors,research,lifescience,medical can refer to measurements of particular circuits as studied by neuroimaging techniques, and/or other

measures validated by animal models or functional neuroimaging (eg, emotion-modulated startle, … The columns of the matrix represent various units (or levels) of analysis that can be used to measure the various constructs, Inhibitors,research,lifescience,medical with the former term preferred to emphasize the integrative approach. The units of analysis are as follows: genes, molecules, cells, circuits, physiology, Inhibitors,research,lifescience,medical behavior, and self-report. Genes, molecules, and cells are self-apparent (although in many cases, direct assessment of molecules and cells in functioning humans remains problematic). The “Circuits” unit of analysis refers to measures that can index the activity of neural circuits, either Olaparib ic50 through functional neuroimaging or through recordings previously validated as circuit indices (eg, fear-potentiated startle). “Physiology” refers to well-established measures that have been validated in assessing various Casein kinase 1 constructs, but that do not measure circuit activity directly (eg, heart rate, Cortisol). “Behavior” may refer either to systematically observed behavior or to performance on a behavioral task such as working memory. There is also a separate column for paradigms, in which scientific tasks that are especially useful for the study of the construct are noted. The cells at the intersections of constructs and columns are populated by research findings.