The Research Domain Criteria (RDoC): an analysis of methodological and conceptual challenges.

In a bold effort to address the longstanding shortcomings of the Diagnostic and Statistical Manual (DSM) framework for the classification and diagnosis of psychopathology, the National Institute of Mental Health recently launched a research program - the Research Domain Criteria (RDoC) - in the hopes of developing an alternative taxonomic system rooted in dysfunctional brain circuitry. Although the RDoC endeavor has considerable promise, it faces several methodological and conceptual challenges, four of which I address here: (a) an overemphasis on biological units and measures, (b) neglect of measurement error, (c) biological and psychometric limitations of endophenotypes, and (d) the distinction between biological predispositions and their behavioral manifestations. Because none of these challenges is in principle insurmountable, I encourage investigators to consider potential remedies for them. RDoC is a calculated gamble that appears to be worth the risk, but its chances of success will be maximized by a thoughtful consideration of hard-won lessons learned--but frequently forgotten--over the past several decades of psychological and psychiatric research.