Research Domain Criteria: A Matrix With Research, Clinical Implications

The NIMH has proposed the use of the Research Domain Criteria (RDoC) matrix to identify the neurobiological basis of mental and substance-use disorders.

Results from national, regional, and global surveys have underscored the burden of illness attributable to mental, neurological, and substance-use disorders (MNS).1 For example, it is now estimated that approximately 20% to 25% of years of life lived with a disability is due to an MNS. Moreover, the aging of the global population and a slower decrease in disability due to noncommunicable diseases relative to mortality indicate that chronic noncommunicable diseases instantiated by MNS will be the global illnesses adversely affecting human capital for the foreseeable future.1

Unfortunately, in contradistinction to other diseases (eg, cardiovascular disease, diabetes, HIV/AIDS), disorders encountered in psychiatry have not witnessed a reduction in mortality.

The dire circumstances facing psychiatry with respect to tremendous morbidity, debased human capital, and staggering mortality have myriad explanations broadly categorized as “macro,” “meso,” and “micro” contexts. For example, from the macro perspective, cultural/societal determinants of mental health (eg, economic hardship, obesity epidemic, homelessness) continue unabated with relatively few national strategies to mitigate such factors. Moreover, an example at the meso level includes, but is not limited to, insufficient access to timely, coordinated, integrated, longitudinal, and accountable care for individuals with MNS.

At the micro level (ie, individual care provider-patient ecosystem), there continues to be persistence of lack of timely diagnosis, a high rate of misdiagnoses, and insufficient application of appropriate stratified medicine. Moreover, in the research sector, psychiatry has not witnessed the introduction of a genuinely novel and innovative pharmacologic treatment in many decades.

Indeed, contemporary psychotropic agents (eg, selective serotonin reuptake inhibitors [SSRIs], second-generation antipsychotics) represent an advance over their pharmacological predecessors (eg, first-generation antipsychotics) insofar as they are generally safer, simpler to administer, better tolerated, and in some cases have differential profiles of efficacy.2 Taken together, however, drug discovery and development in psychiatry have been in a cul-de-sac and are in need of a line in sight.2