Rationale of the RDoC

Perhaps the most powerful impetus for considering RDoC has been the increasing schism between brain research and mental health practice. ^{Footnote 3} One view of why neuroscientific findings have not incurred greater bearing upon the clinical practice of psychiatry is that research studies to date have been predominantly based on inadequately conceptualized psychiatric diagnoses, and have been focused on explaining mechanisms of those diagnostic constructs, rather than seeking to conceptually refine them. ^{Footnote 4} The classification system used in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) was rationalized in that it could afford diagnostic reliability. ^{Footnote 5} However, the DSM system does not enable or facilitate neurobiologic differentiation of psychiatric disorders. ^{Footnote 6} In light of this, the DSM classification system tends to create artificialized categories of mental disorders, which in many ways can obfuscate their complexity, and in so doing, may sustain mental disorders as being conceptually “mythical” in the strictest, and most literal sense (i.e., as “explanatory fictions” that depict and/or provide meaning for very real phenomena and events). ^{Footnote 7} This has had influence both on research, and on its applicability to psychiatric practice. Mixed monothetic/polythetic criteria-based categorical approaches for defining a psychiatric disorder incorporated considerable symptom heterogeneity, comorbidity, and trait variance in study populations, which produced similar degrees of variability in results (even for the most sophisticated assessment techniques of neuroscience), thereby decreasing their reliability, if not validity in certain instances.

To counter such problems, a research framework was required that could be liberated from current diagnostic nosology of the DSM (and International Classification of Disease [ICD]) system, and which would be more inclusive of the growing body of neuroscientific findings addressing structural and functional substrates of psychiatric conditions. Although broad in scope and relatively deep in focus, much of this neuroscientific information is relatively inchoate. ^{Footnote 8} Therefore, organization of the research literature, and resulting utilization of research findings to guide clinically applicable diagnostics and therapeutics, will be important for furthering particular trajectories of empirical inquiry and discovery. Developing, specifying, and prudently employing RDoC may meet such aims.

Undergirding these issues is the complexity of the brain, which is reflected both in the arduousness of attempting to elucidate structural and functional correlates of cognitions, emotions, and behaviors, and also by the diversity of human neurocognitive functions and expressions. Attempts at explaining this diversity have often engaged the biopsychosocial model. ^{Footnote 9} Although views of the biopsychosocial model remain equivocal, a fundamental conceptualization of neuropsychiatric function as obtaining and entailing interactive biological, cognitive, and ecological dimensions is held to be sound. ^{Footnote 10,Footnote 11} Whereas the DSM-5 has maintained certain distinctions between biological and psychological bases of mental illness, the RDoC initiative envisions the biopsychosocial model as an integrative framework, which does not establish rigid separation of physiologic, cognitive, and environmental/ecological factors in and/or as origins of mental illness, but rather fosters and sustains a more interactive and reciprocal approach to these dimensions. In this way, RDoC-based classifications can become “theoretical” views of the etiology of mental illness, in contrast to the DSM-5, which has remained “atheoretical.” The RDoC attribute diversity of behavior and cognition (and emotion) to both variability in/of human genomics and epigenetic modifications ^{Footnote 12} ), which lead to differential gene expression, neurogenesis, and phenotypic maturation of neural networks across the life-span, and interactive effects of neural phenotypes and environmental factors in and across time.

Consistent with an understanding of the hierarchical domains and effects of the biopsychosocial model, the RDoC framework employs a dimensional approach that utilizes seven levels (i.e., units) of analysis: genes, molecules, cells, circuits, physiology, behavior, and self-reports, to conceptually refine several psychological constructs and subconstructs such as “acute threat,” “frustrative non-reward,” or “agency” (see https://www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml for an overview of the RDoC matrix). These constructs will eventually become the fundamental units on which psychopathology will be conceptualized and classified. Paradigmatically, the RDoC approach seeks to investigate how each dimension contributes to a multitude of behavioral trajectories, without (necessarily) considering current psychiatric nosology (i.e., not labeling a behavioral trajectory as normal or abnormal). Each dimension can then serve as a possible point of diagnosis and treatment of psychiatric disorders which, themselves, will be redefined by the RDoC framework. ^{Footnote 13,Footnote 14} Therefore, RDoC could provide a means to develop greater precision within psychiatry, such that psychiatric diagnoses would rely on and reflect neuroscientific data as well as representative clinical signs and symptoms, and psychiatric treatments could become more precise and personalized in their focus on biological and psychosocial factors.

Conceptual and Methodological Challenges to the Use of RDoC

The potential for RDoC to substantively change, if not revolutionize, psychiatric diagnosis and care may be significant;however, it must be emphasized that the phenomena that RDoC are seeking to understand have complex theoretical, practical, and social dimensions. As such, the viability and value of RDoC might warrant a higher level of scrutiny. We believe that this is important, as timely recognition of issues allows a constructive rather than merely a polemical orientation. At present, there is extensive discourse addressing conceptual and methodological challenges generated in and from the RDoC framework. ^{Footnote 15,Footnote 16,Footnote 17,Footnote 18,Footnote 19,Footnote 20,Footnote 21,Footnote 22,Footnote 23,Footnote 24} One of the clearest challenges to using RDoC is to prove the capability that is claimed. In other words, success of the RDoC framework is contingent on the expanding capabilities of neuroscience to accurately describe and define interactive (neural and environmental) mechanisms of psychiatric normality and abnormality.

Current neuroscientific techniques and technologies, and further progress toward using such methods for structural and functional brain mapping, and for developing a variety of interventions, are anticipated as a consequence of recent international efforts in brain science. ^{Footnote 25,Footnote 26} However, the question of whether the tools of neuroscience will be able to objectivize psychiatry to the extent promised by the RDoC approach is a matter of ongoing debate and concern. For example, it remains uncertain if subjective experience can be quantified—or perhaps validated—through the use of assessment neurotechnologies. Although attempts toward this goal have shown some promise, neurotechnology should not be regarded as superseding the importance and value of patients’ first-person experience.

This issue is both practical and philosophical; a subjectivist view of conscious experience incorporates some element of Cartesian dualism, implying that mental events cannot be quantified through the laws of physics. On the other hand, a materialist view of conscious experience does not necessarily account for the “qualia” of mental events, which have been, and continue to be, focal to psychiatric nosology and practices. Kozak and Cuthbert have attempted to find a middle ground between traditional phenomenology and materialism which they refer to as “heterophenomenology.” ^{Footnote 27} As consistent with the concept of heterophenomenology, ^{Footnote 28} the RDoC initiative seeks to include self-report as a unit of analysis, but accords self-report data no special precedence among different classes and types of measurement, and maintains theoretical neutrality among employed units of analysis.

In this light, the heterophenomenologic orientation may be particularly well suited to achieving the RDoC goal of elevating contributions of neuroscience to be constituent to an integrative approach to psychopathology. But this also is not without challenges, the most notable of these, we believe, being the issue of dissonance (i.e., modest covariation) among units of analysis, which can lead to decreased convergent validity of the constructs of the RDoC framework. ^{Footnote 29} We posit that this likely reflects an “explanatory gap,” ^{Footnote 30} and prompts the question of whether clinical applications and use of RDoC should be kept in abeyance until this explanatory gap is bridged in some way(s). If the RDoC framework is prematurely implemented in clinical realms, psychiatric practice may witness a misalignment of subjective self-reports and objective data. Will RDoC-based nosology maintain neutrality among units of analysis in the inference of diagnosis, or will it give preference to subjective symptoms?

We posit that such dissonance and this “explanatory gap” may render the RDoC-based stance of maintaining theoretical neutrality among units of analysis somewhat problematic. Perhaps the solution to this problem lies in reducing the extant explanatory gap between objective features of the nervous system and subjective experiences of cognition and emotions. However, it is crucial to ask if this gap can and will be bridged, and in the event, how long will this take, and what of clinical diagnosis and care in the interim? Answering these queries is critical in view of the current status of psychiatry and mental health, and the potential worldwide impact of the RDoC initiative. However, such attempts at cutting through the problem of the explanatory gap may be double-edged: on the one side, devoting attention to methods and metrics to de-limit dissonance and the explanatory gap will foster more dedicated involvement in fortifying the validity and viability of RDoC; whereas on the other, such efforts may divert research foci away from the assessment and treatment of mental health problems, per se.

In our view, the RDoC framework represents an organized and potentially effective approach to describing and defining psychiatric states. However, axiomatic to our stance (if not the very notion of RDoC) are questions of if and how such criteria may be directed and utilized toward both the “bench” as well as “bedside” aspects (and needs) of psychiatry. The neurosciences have certainly shown rapid and broad growth; however, there is some debate as to how research developments in the brain sciences can and should be applied in clinical psychiatry, ^{Footnote 3} and there has been criticism of the NIMH’s policy of shifting its funding away from DSM-based clinical research toward RDoC-oriented studies. ^{Footnote 31,Footnote 32}

To wit, a more balanced approach, which considers both current mental health problems and RDoC objectives may be required. Thus, we concur with Patrick and Hajcak ^{Footnote 33} that strategic steps should be taken to align RDoC research with clinical problems encountered in psychiatric practice. For this purpose, current mental health problems need to be defined and contextualized within the RDoC framework. However, it is important to ask how RDoC will discern abnormality from normality. Will distinctions be established at the extremes of neural, cognitive, and/or behavioral spectra, or will thresholds be drawn based upon psychosociocultural norms and individual subjective experiences? Conceptualization of mental phenomena will require special attention to environmental and social contexts in which an individual’s brain develops and functions. Social values will certainly continue to play a role in defining mental disorders. ^{Footnote 34} Therefore, it is probable that the conceptual and ethical issues related to the definition of mental disorder, such as what constitutes normality and abnormality, functionality or dysfunction; concerns about a growing medicalization of behavior and about what represents a treatment, an enablement, and/or an enhancement, will need to be considered and addressed when seeking to employ RDoC-based psychiatric nosology. ^{Footnote 35,Footnote 36}

At present, it is unclear how RDoC constructs will map to psychiatric symptoms and disorders. Will RDoC constructs such as “agency” or “self-knowledge” become the explanans of complex mental phenomena such as delusions, depersonalization, or personal identity? Although mechanistic reductionism (i.e., approaching complex phenomena through their components) may be a valid approach for attempting to understand mental function and disorders, RDoC must maintain the complexities inherent in mental illness and the sufferings of patients, as commonly encountered in clinical practice. Thus, both “bottom up” (e.g., identifying genotypic and phenotypic variables contributory to particular psychopathologies and/or their treatment), and “top down” approaches (e.g., studying the effects of environment and psychotherapy on functional and structural aspects of the brain) will be essential in this regard. ^{Footnote 37} Moreover, given the plastic nature of the brain, the integration of psychosocial and environmental contexts with neurobiological processes in the RDoC framework remains challenging; however, this may also present an opportunity to develop a more ecologically relevant view of neuropsychiatric function and dysfunction. Big data approaches could offer some promise in integrating a massive amount of differing types and levels of information (i.e., from the cellular to the social); ^{Footnote 38} however, these, too, are not without issues or problems (the scope and extent of which are beyond the aim and focus of this article; see DiEuliis and Giordano ^{Footnote 39} for overview).

It is worth speculating whether the ability of RDoC-based psychiatric nosology could replace clinical utility of the DSM-5. The “operational revolution” brought on by the DSM-III increased the relative value of its constructs and categorizations to psychiatrists, psychotherapists, and mental health counselors. ^{Footnote 40} Most of the constructs of RDoC have their origins in cognitive neuroscience, and their utility in and for clinical psychiatry remains debatable. Therefore, any attempt at clinical application of these constructs would require development of instruments to measure them in effective ways. In light of this, more widespread implementation of a neuroscientifically based classification system might mandate increased focus on the neurosciences in medical education and psychiatry residency curricula. ^{Footnote 41} However, any such effort should also incorporate a biopsychosocial orientation that accurately nests neurobiological functions (and dysfunction) within the reality of an embodied, socioenvironmentally embedded individual who is the psychiatric patient.

Neuroethical and Social Implications of RDoC-Based Psychiatric Nosology

Perhaps the most salient question is whether medicine and society are ready for a truly neuroscientifically based, integrative psychiatry. In posing this question, we will engage a brief thought experiment: Imagine an era of precision psychiatry wherein the potential occurrence of a disorder can be predicted well before symptomatic onset. Even if researchers and clinicians are clear about the probabilistic nature of biomarkers, it would be easy for the public to overestimate their predictive ability. For example, it might become common practice to label children and adolescents “at risk” for certain disorders, or to even consider “at risk” to be synonymous with a prodromal phase of a particular disease. Although such classifications may enable early—and preventive—intervention, they could also lead to stigmatization and distinctions in social regard and treatment even before the presentation of signs and symptoms. Such bias could evoke social discrimination, rejection, self-isolation, and loss of self-esteem for those persons who present accepted “indicators” of disorders, but are not yet considered to be patients. ^{Footnote 42} Such characterizations could affect social and familial attitudes and regard, family and community dynamics, and public, scholastic, occupational, and—given the possibility of insurance companies regarding such conditions as “preexisting”—even the medical treatment of “at risk” individuals. ^{Footnote 43}

Given the potential for these personal and social effects, we assert that it will be important to ascertain the extent to which neuroscience research can affect certain aspects of individual and public life. ^{Footnote 44,Footnote 45} Obviously there are calls for neuroscientific research to be directed toward identifying objective markers of socially harmful behaviors, such as violence and criminality, in order to employ neuropsychiatry as—and in—a more expansive construct and execution of public good (i.e., as a means to effect public safety). ^{Footnote 46} However, postures of employing neuropsychiatry for “delivering humanity from evil” are likely to witness conflicts that arise in the juxtapositioning of an ethos of care with concerns for social justice, and respect for individual autonomy. ^{Footnote 47} Similarly, applications of neuroscientific research that focus on psychopathologies relevant to criminal law are likely to sustain current, and invoke new, debates regarding free will, capacity, and whether the use of neuropsychiatric intervention constitutes rehabilitation or a masked form of retribution. ^{Footnote 48} Ethical issues related use of neuroscientific approaches for cognitive performance optimization and/or emotional modification (i.e., “cosmetic neuropsychiatry”) will also arise. ^{Footnote 49,Footnote 50}

The pace of neuroscientific research and the urgency of calls for its translation to improve neuropsychiatric diagnoses and treatment(s) mitigate a “wait and see” attitude, or the use of a simple precautionary principle to guide the use of brain science in clinical psychiatry. Rather, we have argued that such issues call for a preparatory neuroethical stance that can be used to (1) realistically assess the potential of objective measurements of neurotechnology to be used in clinical realms; (2) chart trajectories of their use and misuse; (3) identify potential problems and issues arising from their use and misuse; and (4) develop guidelines and approaches to address these problems and issues before or early in their development. ^{Footnote 51} Early public engagement and interdisciplinary interactions among neuroscience researchers, psychiatrists, social scientists, ethicists, legal scholars, and policymakers will be essential for both productive discourse and the formulation of reasoned outcomes.

However, even if consensus among these groups is reached about how neuroscientific information should be used in clinical psychiatry, it is important to recognize that commercial entities can utilize neuropsychiatric data to define, depict, and perhaps predict cognitions, emotions, and behaviors for purposes that are aligned more with business ends than those of medicine. ^{Footnote 52} Commercial entities can use algorithms to detect profiles of people with mental illnesses to effect profiling and bias (if not frank discrimination) in employment and in the provision (and/or denial) of health insurance. In the United States, the Genetic Information Non-Discrimination Act (GINA) protects against any such bias based on genetic information. We believe that similar legislation, such as the proposed Neuro Information Non-Discrimination Act (NINA) would be of value to protect individuals against bias educed by neuropsychiatric data. ^{Footnote 53} Last, but certainly not least, a mental health agenda of this magnitude necessitates (if not obligates) increased funding initiatives, and the appropriation and allocation of resources as required to both initiate and sustain these multidisciplinary efforts. Mental health reforms, such as the United States’ Mental Health Reform Act of 2016, are aimed at integrating mental health and primary care, and at increasing insurance coverage, without discrimination, as needed to implement equitable efforts in psychiatric diagnosis and treatment. However, it remains to be seen whether and in what ways healthcare reforms and funding of medical and scientific research will be sustained or altered as a consequence of shifting priorities of new political administrations in the United States, and elsewhere.