RDoCs redux

Abstract

We are delighted to share in the debate about the RDoC program, as we feel some responsibility for its birth. Indeed, the notion articulated in RDoC to inform "future versions of psychiatric nosologies based upon neuroscience and behavioral science rather than descriptive phenomenology", by providing "a framework for conducting research in terms of fundamental circuit-based behavioral dimensions that cut across traditional diagnostic categories" 1, is a direct outgrowth of studies that began in the Clinical Brain Disorders Branch of the Intramural Research Program of the National Institute for Mental Health (NIMH) at St. Elizabeth's Hospital in the early 1980s. This body of work led to the creation of the Genes, Cognition and Psychosis program, an interdisciplinary research program which in its title recognized that the biology of psychopathology was not linked to diagnostic nomenclature. The work of this program in identifying mechanisms in the brain by which risk factors influenced biological susceptibility was a foundation of the Strategic Plan launched by the NIMH in 2008 and in which the RDoC plan was proffered. Given our experience with work that forms so much of the rationale for RDoC, we should be enthusiastic. So, why are we not? Actually, the debate between "lumpers" and "splitters", whether in the realms of descriptive psychopathology or in brain imaging measurements or in genetics, has been going on literally for over a century in psychiatry. The RDoC project claims to be a new and enlightened way to split and then lump, because it argues that the neuroscience and genetics of psychiatric disorders open new arenas for such progress. This sounds really good, but to paraphrase a popular beer advertisement in the USA, does it taste great? We see the main concerns about the RDoC mindset not with its conceptual foundations, but with its reliance on the presumed validity of the behavioral, neural functional and genetic dimensions it highlights as fundamental to a revision of psychiatric nomenclature. Ultimately, any revision of psychiatric diagnosis, which clearly is the RDoC goal, must be better than the existing system, better in the sense of what diagnosis is about. Diagnosis is primarily an instrument used by clinicians for two primary purposes: to predict the natural history of an illness and to predict the most appropriate treatment. This will be the standard also for RDoC, if its long-term goal of replacing existing diagnostic practices is to be realized. Even clear and important dimensions of behavior and its reward-based underpinnings may have unexpected complexities when viewed through the RDoC lens. In an incisive and elegant study, Gold et al 2 demonstrated that negative symptoms in schizophrenia are associated with overestimating the cost (or effort) involved in attaining an outcome. One could easily view this as a metric or dimension, suggestive of "degrees" of negative symptoms. One can imagine elegant neuroimaging studies of effort estimation showing varying engagement of prefrontal, insular, and striatal function. Cuthbert's suggestion that a good research study would be to explore such behavioral and neural system dimensions across current diagnostic groups and in subjects without psychiatric diagnoses presents a daunting conundrum. For example, "overestimating the cost (or effort) involved in attaining an outcome" also seems to be a suitable operational definition of laziness, as used by lay individuals. Thus, an important question is whether this or any of the RDoC dimensions have the same meaning when associated with schizophrenia qua schizophrenia, or if they are observed across other diagnoses and in a spectrum of otherwise normal, albeit, lazy individuals. Moreover, would the neural systems and genomics that are associated with this set of behaviors be the same in all cases? Several recent papers focus on this issue. They suggest, for example, that mechanisms for auditory hallucinations in otherwise healthy functioning individuals (so called "voice-hearers") may be different than the mechanisms associated with such symptoms in schizophrenia 3. It has become increasingly popular to believe that similar patterns of brain activity in patients with psychiatric illness and in some non-psychiatric research samples underlie RDoC-type dimensions of psychopathology. These studies are based on specific protocols that elicit physiological responses critically dependent on the context. It is an old saying in the functional neuroimaging research lexicon that functional neuroimaging data reflect what the brain was doing during the imaging protocol, but the challenge for the investigator is to figure out what the brain was actually doing. The meaning of this saying is that patterns of engagement of brain functional systems during an imaging experiment do not necessarily reflect a specific or even definable brain state. A clear illustration of this is the current fascination with the so-called