Clashing Diagnostic Approaches: DSM-ICD Versus RDoC.

Since at least the middle of the past century, one overarching model of psychiatric classification has reigned supreme, namely, that of the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Related Health Problems (herein referred to as DSM-ICD). This DSM-ICD approach embraces an Aristotelian view of mental disorders as largely discrete entities that are characterized by distinctive signs, symptoms, and natural histories. Over the past several years, however, a competing vision, namely, the Research Domain Criteria (RDoC) initiative launched by the National Institute of Mental Health, has emerged in response to accumulating anomalies within the DSM-ICD system. In contrast to DSM-ICD, RDoC embraces a Galilean view of psychopathology as the product of dysfunctions in neural circuitry. RDoC appears to be a valuable endeavor that holds out the long-term promise of an alternative system of mental illness classification. We delineate three sets of pressing challenges--conceptual, methodological, and logistical/pragmatic--that must be addressed for RDoC to realize its scientific potential. We conclude with a call for further research, including investigation of a rapprochement between Aristotelian and Galilean approaches to psychiatric classification.

The National Institute of Mental Health Research Domain Criteria: A Bridge Too Far.

The National Institute of Mental Health is actively promoting Research Domain Criteria as a new model for the research on mental disorders. Research Domain Criteria approaches disorders through a matrix, linking units of analysis with domains, based on the assumption that psychopathology reflects abnormal connectivity in the brain. This review suggests that the Research Domain Criteria perspective is likely to fail to provide an adequate basis for clinical psychiatric theory and practice. First, it uses models from neuroscience that are insufficiently developed. Second, it is based on the premise that mental phenomena and mental disorders can be reduced to neural activity, without consideration of cognition, experience, and social interaction. Third, it downplays psychosocial factors in psychopathology and treatment. Research Domain Criteria may therefore prove inadequate for providing a neuroscientific basis for psychiatric nosology and treatment and needs to be supplemented with a broader view that incorporates insights from social sciences, psychology, and phenomenology.

Challenges and strategies in helping the DSM become more dimensional and empirically based.

The DSM-5 creation process and outcome underlines a core tension in psychiatry between empirical evidence that mental pathologies tend to be dimensional and a historical emphasis on delineating categorical disorders to frame psychiatric thinking. The DSM has been slow to reflect dimensional evidence because doing so is often perceived as a disruptive paradigm shift. As a result, other authorities are making this shift, circumventing the DSM in the process. For example, through the Research Domain Criteria (RDoC), NIMH now encourages investigators to focus on a dimensional and neuroscientific conceptualization of mental disorder research. Fortunately, the DSM-5 contains a dimensional model of maladaptive personality traits that provides clinical descriptors that align conceptually with the neuroscience-based dimensions delineated in the RDoC and in basic science research. Through frameworks such as the DSM-5 trait model, the DSM can evolve to better incorporate evidence of the dimensionality of mental disorder.

Beyond the DSM: development of a transdiagnostic psychiatric neuroscience course.

OBJECTIVE: Clinical and neurobiological data suggest that psychiatric disorders, as traditionally defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), are (1) more comorbid than expected by chance, (2) often share neurobiological signatures, and (3) reflect alterations across multiple brain systems that mediate particular mental processes. As such, emerging conceptualizations such at the National Institute of Mental Health's Research Domain Criteria Project (RDoC) have suggested that a different way to understand psychopathology may be with respect to the degree of dysfunction in each of these brain systems, seen dimensionally, which both cross traditional diagnostic boundaries and extend to a healthy range of functioning. At present, however, this scientific perspective has not been incorporated into neuroscience education in psychiatry, nor has its relationship to clinical care been made clear. METHODS: We describe the rationale and implementation of a reformulated neuroscience course given to psychiatric residents at Stanford University centered on the conceptual framework of RDoC. Data are presented on resident feedback before and after revision of the course. RESULTS: A clear motivation and rationale exists for teaching neuroscience in a transdiagnostic framework. This course was taken up well by the residents, with overall feedback significantly more positive than that prior to the course revision. CONCLUSION: This "proof of concept" neuroscience course illustrates a potential route for bridging between rapid advances in psychiatric neuroscience and the clinical education for trainees not otherwise versed in neuroscience but who are needed for scientific advances to translate to the clinic. The promise of this approach may be in part related to the similarity between this framework and problem-based approaches common in routine clinical care. In such approaches, clinicians focus on the expressed complaints of their individual patient and identify specific symptoms as the target of treatment--symptoms which are presumably the expression of dysfunction in specific brain systems.

Mind the gap: neuroscience literacy and the next generation of psychiatrists.

The National Institute of Mental Health seeks to address the gap between modern neuroscience and psychiatric training. The authors describe a two-pronged approach: first, to identify and support trainees in clinical neuroscience and second, to promote neuroscience literacy in psychiatric residency programs.

The changing face of Parkinson's disease-associated psychosis: a cross-sectional study based on the new NINDS-NIMH criteria.

New criteria for Parkinson's disease-associated psychosis (PDAP) were recently proposed by a NINDS-NIMH working group. We assessed 116 consecutive unselected outpatients with PD for the existence of psychotic symptoms during the previous month, using a structured questionnaire covering the whole spectrum of PDAP symptoms. Hallucinations occurred in 42% of the patients (visual: 16%; nonvisual: 35%), delusions in 4%, and minor symptoms in 45% (sense of presence, visual illusions, or passage hallucinations). The prevalence of PDAP was 43% when the usual definition was used (hallucinations and/or delusions) and 60% when the NINDS-NIHM criteria were used. Correlations between PDAP and patient characteristics varied with the definition of PDAP. These findings suggest that the epidemiology of PDAP should be re-evaluated with the new criteria. Minor symptoms and nonvisual hallucinations are an important part of the PDAP spectrum, which has commonly been restricted to visual hallucinations and delusions.

Can RDoC Help Find Order in Thought Disorder?

Thought disorder is a pernicious and nonspecific aspect of numerous serious mental illnesses (SMIs) and related conditions. Despite decades of empirical research on thought disorder, our present understanding of it is poor, our clinical assessments focus on a limited set of extreme behaviors, and treatments are palliative at best. Applying a Research Domain Criteria (RDoC) framework to thought disorder research offers advantages to explicate its phenotype; isolate its mechanisms; and develop more effective assessments, treatments, and potential cures. In this commentary, we discuss ways in which thought disorder can be understood within the RDoC framework. We propose operationalizing thought disorder within the RDoC construct of language using psycholinguistic sciences, to help objectify and quantify language within individuals; technologically sophisticated paradigms, to allow naturalistic behavioral sampling techniques with unprecedented ecological validity; and computational modeling, to account for a network of interconnected and dynamic linguistic, cognitive, affective, and social functions. We also highlight challenges for understanding thought disorder within an RDoC framework. Thought disorder likely does not occur as an isomorphic dysfunction in a single RDoC construct, but rather, as multiple potential dysfunctions in a network of RDoC constructs. Moreover, thought disorder is dynamic over time and context within individuals. In sum, RDoC is a useful framework to integrate multidisciplinary research efforts aimed at operationalizing, understanding, and ameliorating thought disorder.

Psychotherapy Research and the NIMH: An Either/Or or Both/And Research Agenda?

There is a need for psychotherapy research to determine the effective, nonspecific or shared elements of psychotherapy regardless of therapy school. In an apparent "either/or" rather than "both/and" choice, the National Institute of Mental Health (NIMH) has committed its research resources to study of neural mechanisms and biomarkers, while greatly reducing funding for research into clinical methods, including psychotherapy. This column explores the potential effect of this decision on patient care and reviews questions raised by some about whether the underlying "big idea" behind the NIMH research approach is supported by the results of several decades of brain and genomics research. Patients are left to hope for clinically meaningful research findings concerning brain or gene mechanisms of mental disorders, as if they are just around the corner, when the actual benefit of such research likely remains decades away.

Potential Applications of the National Institute of Mental Health's Research Domain Criteria (RDoC) to Clinical Psychiatric Practice: How RDoC Might Be Used in Assessment, Diagnostic Processes, Case Formulation, Treatment Planning, and Clinical Notes.

Offering a new framework for understanding and studying basic dimensions of normal and abnormal human functioning and mental disorders, the National Institute of Mental Health (NIMH) has initiated the Research Domain Criteria (RDoC) project in which a series of higher order domains, representing major systems of emotion, cognition, motivation, and social behavior, and their constituent operationally defined constructs serve as organizing templates for further research and inquiry, eg, to discover validated biomarkers and endophenotypes. Cutting across traditional DSM diagnoses, the domains are defined as Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Systems for Social Processes, and Arousal/Regulatory Systems. To inform educators, trainees, and practitioners about RDoC, alert them to potential practical applications, and encourage their broad exploration in clinical settings, this article reviews the RDoC domains and their subsystem constructs with regard to potential current clinical considerations and applications. We describe ways in which the RDoC domains and constructs offer transdiagnostic frameworks for complementing traditional practice; suggest clinical questions to help elucidate salient information; and, translating RDoC domains and constructs headings into clinically friendly language, offer a template for the psychiatric review of systems that can serve in clinical notes.

Self-report indicators of negative valence constructs within the research domain criteria (RDoC): A critical review.

BACKGROUND: In 2010, the National Institute of Mental Health (NIMH) created the Research Domain Criteria (RDoC), a research framework for integrating multiple units of information to explicate basic dimensions of functioning underlying both adaptive and maladaptive behavior. Our goal in this review is to evaluate self-report indicators of negative valence systems constructs within RDoC. METHODS: We review the content and correlates of several of the most popular self-report measures currently classified within the negative valence systems in the RDoC matrix, using both our own data and previously published results. We use these data to evaluate whether these measures are appropriately placed; in addition, wherever possible, we recommend better alternatives to assess key RDoC constructs. RESULTS: Our findings indicate that many of the currently listed self-report measures are misplaced. Specifically, our data reveal that some of the purported fear scales are better conceptualized as measures of anxiety and/or anxious arousal. In addition, none of the currently listed measures of frustrative nonreward is a clear, unambiguous indicator of that construct. LIMITATIONS: The RDoC matrix currently does not list any specific measures of either loss or sustained threat, which makes it difficult to identify appropriate measures of these constructs. In many cases, the specificity/discriminant validity of proposed measures remains uncertain. CONCLUSIONS: Researchers wanting to include self-report measures of negative valence constructs currently receive little guidance from the RDoC matrix. Future assessment work should be oriented toward the development of measures that are explicitly designed to assess these RDoC constructs.

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

A New Empirical Definition of Major Depressive Episode Recovery and Its Positive Impact on Future Course of Illness.

OBJECTIVE: To provide the first head-to-head test of the predictive validity of 2 resolution levels included in the current consensus definition of major depressive episode (MDE) recovery and provide an empirically based, clinically useful definition of the end of an MDE. METHOD: 322 participants entering the National Institute of Mental Health Collaborative Depression Study with MDE (diagnosed by Research Diagnostic Criteria) in 1978-1981, and followed thereafter for up to 31 years, were divided into those with 8 consecutive weeks of asymptomatic MDE recovery or residual subsyndromal depressive symptom (SSD) resolution of their index MDE. These 2 levels of recovery were defined based on weekly symptom status on all depressive conditions, assessed by Longitudinal Interval Follow-Up Evaluation (LIFE) interviews conducted every 6 months. Primary measures of validity of these 2 alternative definitions were first well interval duration and long-term depressive illness burden. Groups were also compared on clinical variables, antidepressant treatment, and psychosocial function. RESULTS: 61.2% of subjects recovered asymptomatically from their index MDE. By survival analysis, they remained free of a depressive episode relapse or recurrence 4.2 times longer than those with SSD resolution (median = 135 vs 32 weeks; χ² = 70.65; P < .0001). This was not attributable to a difference in intensity of antidepressant medication. Compared to asymptomatic recovery, SSD resolution was associated with significantly longer and more severe index MDEs, with more miscellaneous psychopathology as well as increased long-term psychosocial dysfunction and a greater depressive illness burden during the ensuing 10 or 20 years. Asymptomatic MDE resolution was a stronger predictor of time well than any of 18 other predictors, singly or combined. Eight consecutive weeks of asymptomatic recovery had 93% overlap with a 4-week definition and conferred little benefit over 4 weeks. CONCLUSIONS: Four consecutive weeks of asymptomatic recovery defines the end of an MDE and the beginning of a stable well state with improved psychosocial function. Residual symptom resolution is a continuation of an active state of the episode, not the end of an MDE.

The National Institute of Mental Health Research Domain Criteria and Clinical Research in Child and Adolescent Psychiatry.

OBJECTIVE: This review discusses the relevance of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) to clinical research in child and adolescent psychiatry. METHOD: We summarize the characteristics of the NIMH RDoC project and then provide examples of RDoC designs that are of relevance to clinical investigators in child and adolescent psychiatry. The final section addresses questions regarding the impact of RDoC on clinical care. RESULTS: RDoC encourages investigators to investigate psychopathology dimensionally: greater or lesser degrees of healthy/adapted functioning of neurobiological, cognitive, and behavioral processes (constructs) that cut across current diagnostic categories. Elucidation of the developmental components of RDoC constructs is needed to ensure they are fully validated. Integrating RDoC approaches into clinical research of child and adolescent psychopathology is contributing to our understanding of development as an aspect of the heterogeneity within DSM disorders and commonalities across seemingly disparate disorders. Continued efforts promise to also explain the processes that lead to mental illness in at-risk populations. CONCLUSION: Incorporating an RDoC approach in clinical research in child and adolescent psychiatry promises to be a fruitful avenue of research into the root causes and manifestations of mental illness, which will eventually lead to more precise treatments. Although the long-term aspiration of RDoC is to help reduce the burden of suffering for those with mental illnesses, it is not intended to be used for practical clinical purposes at this early stage.

Operationalizing NIMH Research Domain Criteria (RDoC) in naturalistic clinical settings.

Recently, the National Institute of Mental Health (NIMH) introduced the Research Domain Criteria (RDoC) initiative to address two major challenges facing the field of psychiatry: (1) the lack of new effective personalized treatments for psychiatric disorders, and (2) the limitations associated with categorically defined psychiatric disorders. Although the potential of RDoC to revolutionize personalized psychiatric medicine and psychiatric nosology has been acknowledged, it is unclear how to implement RDoC in naturalistic clinical settings as part of routine outcomes research. In this article, the authors present the major RDoC principles and then show how these principles are operationalized in The Menninger Clinic's McNair Initiative for Neuroscience Discovery-Menninger & Baylor College of Medicine (MIND-MB) study. The authors discuss how RDoC-informed outcomes-based assessment in clinical settings can transform personalized clinical care through multimodal treatments.

Report card on the National Plan for Research on Child and Adolescent Mental Disorders. The midway point.

A strong argument can be made that given the long-term impact of child and adolescent mental disorders, it is essential for the National Institutes of Health and other funding agencies in the public and private sectors to identify this as a priority in need of greater financial support. This document uses data provided by the National Institute of Mental Health and other sources to assess the impact of the National Plan for Research on Child and Adolescent Mental Disorders that was presented to Congress in 1990. Major gains are noted, particularly in the areas of services research and prevention. Investment in research training and career development has been modest and many deserving career development proposals have not been funded. A major shortcoming in the implementation of the national plan, thus far, has been that the National Institute of Mental Health has not yet taken steps to inform the public concerning the nature and impact of child and adolescent mental disorders. This report ends with an examination of the declining indicators of the status of children in the United States and the conclusion that concerted efforts are needed to educate all segments of society concerning the latest knowledge about these potentially devastating conditions and what can be done to prevent and treat them. Our most precious natural resource, our children and youth, is in jeopardy. It is time to build on advances in related fields of scientific inquiry and to continue to develop the knowledge-base needed to intervene effectively and lessen the enormous human and financial costs associated with these conditions.

Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria.

To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.

Beyond the question of placebo controls: ethical issues in psychopharmacological drug studies.

RATIONALE: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup. OBJECTIVES: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines. METHODS: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature. RESULTS: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions. CONCLUSIONS: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.