The lack of transformative therapeutics in psychiatry has several determinants, notably the absence of a consensually agreed-upon pathogenetic model, unavailability of discrete, specific pathophysiologic processes, and multifactorial causation. Moreover, no psychopathologic feature is pathognomonic; instead, all psychopathology can be conceptualized as transnosological.

The need for a consensus neuropathology in psychiatry is a clarion call for novel treatment approaches, and provided the impetus for the National Institute of Mental Health to propose the Research Domain Criteria (RDoC) matrix. The RDoC broadly aims to elucidate the neurobiological substrates subserving brain disorders.3-5 It is hoped that achieving this objective will provide fertile ground for discovering, purposing, and developing treatments that are not only symptom mitigating, but are also disease modifying.


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The RDoC matrix has an empirically supported assumption that all psychopathology described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) can be reduced into discrete and partially overlapping domains. An explicit deficiency of the DSM-5 taxonomy is that inorganic divisions exist between mental disorders across the developmental trajectory. The RDoC takes an agnostic approach diagnostically and instead categorizes psychopathology by its phenomenology and neurobiological substrates.

Broadly speaking, the RDoC disaggregates psychopathology into 5 domains: negative valence systems, positive valence systems, general cognitive processes, social cognition, and arousal. At first glance, the vocabulary of RDoC appears novel and somewhat foreign. On more detailed review, however, the domain categories described in RDoC have tremendous empirical evidence supporting their existence and have face validity in the clinical ecosystem.

For example, a theme overarching many RDoC domains is a core disturbance in several aspects of cognitive function. This has tremendous face validity insofar as a deficit in cognitive function affects all brain illnesses across the developmental trajectory; this is supported by contemporary conceptualization of neurodevelopmental/neurodegenerative aspects of mental disorders. Moreover, the role disability highly associated with MNS is in many cases a direct consequence of impairment in role function.