Research Domain Criteria Framework Research Articles

Advancing Translational Research Using NIMH Research Domain Criteria and Computational Methods

The NIMH Research Domain Criteria (RDoC) can aid in the translation of integrative neuroscience. We argue that the RDoC framework, with its emphasis on integration across units of analysis, leveraged with computational approaches, can organize intermediary treatment targets and clinical outcomes, augmenting the translational stream.

The Importance of Sensory Processing in Mental Health: A Proposed Addition to the Research Domain Criteria (RDoC) and Suggestions for RDoC 2.0.

The time is ripe to integrate burgeoning evidence of the important role of sensory and motor functioning in mental health within the National Institute of Mental Health’s [NIMH] Research Domain Criteria [RDoC] framework (National Institute of Mental Health, n.d.a), a multi-dimensional method of characterizing mental functioning in health and disease across all neurobiological levels of analysis ranging from genetic to behavioral. As the importance of motor processing in psychopathology has been recognized (Bernard and Mittal, 2015; Garvey and Cuthbert, 2017; National Institute of Mental Health, 2019), here we focus on sensory processing. First, we review the current design of the RDoC matrix, noting sensory features missing despite their prevalence in multiple mental illnesses. We identify two missing classes of sensory symptoms that we widely define as (1) sensory processing, including sensory sensitivity and active sensing, and (2) domains of perceptual signaling, including interoception and proprioception, which are currently absent or underdeveloped in the perception construct of the cognitive systems domain. Then, we describe the neurobiological basis of these psychological constructs and examine why these sensory features are important for understanding psychopathology. Where appropriate, we examine links between sensory processing and the domains currently included in the RDoC matrix. Throughout, we emphasize how the addition of these sensory features to the RDoC matrix is important for understanding a range of mental health disorders. We conclude with the suggestion that a separate sensation and perception domain can enhance the current RDoC framework, while discussing what we see as important principles and promising directions for the future development and use of the RDoC.

Advancing addiction research through expert consensus.

The Delphi review by Yücel and colleagues identifies important gaps in typical assessments of substance use disorder and provides a commendable example of expert consensus that could be employed in other domains such as identifying the critical neurobiological or environmental contributors to dependence. Research into human addiction is difficult. It is broad in its scope, ranging from genetics to culture, it seems destined to yield messy and complicated insights given the very many interacting factors that probably contribute to dependence, and it is often controversial, touching on matters of personal responsibility and socio-economic disadvantage. So broad a domain of human behavior may appear daunting for researchers wishing to investigate what they hope are the core characteristics of addiction. Yücel and colleagues have done the field a great service by coming together as a large team of addiction experts to develop a consensus on what these core characteristics may be 1. They explored the extent to which these core attributes of addiction can, and cannot, be described by the US National Institutes of Mental Health Research Domain Criteria (RDoC) transdiagnostic constructs. Their endeavors identified five constructs from the Positive Valence System, one from the Cognitive Control System and an additional one suggested by their expert panel that they submit are the most relevant to substance and behavioral addictions. Further, they separately addressed characteristics associated with the onset of substance use and vulnerability to dependence from those associated with current dependence. The paper draws useful attention to inadequacies in the assessment batteries that research studies typically employ. Specifically, they note the shortage of validated measures of the Positive Valence system, especially reward sensitivity, which they identify as of primary importance for dependence. The RDoC framework identifies a core set of dimensional and transdiagnostic constructs which can serve as fundamental for describing a wide range of psychiatric disorders. One concern with any typology is whether it might prove restrictive but, notably, the expert panel identified an additional feature not represented in RDoC (compulsivity), while also acknowledging the biological reductionism of the RDoC framework as a potential limitation. A critical consideration is the extent to which this Delphi study yields testable hypotheses or suggests valuable future directions. For example, might psychological profiles that stress these dimensions be shown to have better predictive power (of use initiation, of severity of use, of relapse) than existing batteries? Might distinct profiles based on this particular subset of RDoC constructs be identified for users of different substances? This Delphi review considered ongoing current use and relapse together under chronicity. Is it possible that there are particular processes related to the successful avoidance of relapse (e.g. goal maintenance or performance monitoring from the Cognitive domain) that might have been identified should a distinction between the two be made? Importantly, are the identified constructs of equal importance? Is compromised functioning on each construct characteristic of all substance users or do different subsets of features apply to different subgroups of users, suggesting a range of mechanisms applying to dependence ‘subtypes?’ Another line of enquiry, motivated by the prevalence of comorbidities in dependence, is what can be said about the sensitivity and specificity of the profile that emerges from this identification of primary factors in addiction? Is it particular to addiction or might it also identify vulnerability for other psychopathologies? The strength of this Delphi review paper is that it makes all these questions more tractable. By reducing the complexity of the psychological processes underlying addiction to a finite number of core characteristics, these building blocks of addiction might help researchers in how they conceptualize and operationalize the questions above. In time, this research will reveal if these building blocks prove adequate or require modification or supplementation with others. This expert-consensus approach has great potential to be applied to other domains. There is a very rich body of work investigating the neurobiology of dependence, but is there a consensus on what are the critical brain systems linked to vulnerability, to chronic use, or to relapse? Intra-individual neurobiological and psychological processes function within families, environments and cultures, but is there any consensus on which aspects of these larger domains confer added risk or protection on early use, dependence or abstinence? Experts in these domains, motivated by the example of Yücel and colleagues, may be encouraged to tackle these questions next. None.

The PRISM project: Social withdrawal from an RDoC perspective

The PRISM (Psychiatric Ratings using Intermediate Stratified Markers) project was funded under the auspices of the European Union Innovative Medicine Initiative (EU-IMI) to explore quantitative approaches to the biological and behavioral aspects of neuropsychiatric disorders. PRISM focuses specifically on social withdrawal, although its principles are applicable to a wide range of disorders. This commentary explores some of the major aspects of the PRISM design from the perspective of the Research Domain Criteria (RDoC) project initiated by the National Institute of Mental Health. PRISM represents an apt exemplar of the principles developed in the RDoC framework, with the potential to contribute palpable advances in precision diagnosis and innovative approaches to treatment development.

Advancing the study of sluggish cognitive tempo via DSM, RDoC, and hierarchical models of psychopathology.

Sluggish cognitive tempo (SCT) is separable from attention-deficit/hyperactivity disorder (ADHD) and other psychopathologies, and growing evidence demonstrates SCT to be associated with impairment in both children and adults. However, it remains unclear how SCT should optimally be conceptualized. In this article, we argue that multiple models of psychopathology should be leveraged to make substantive advances to our understanding of SCT. Both categorical and dimensional approaches should be used, including the Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology, the Research Domain Criteria (RDoC) initiative, and hierarchical models of psychopathology. Studies are needed to determine whether individuals categorized with SCT can be reliably identified and differentiated from individuals without SCT in pathophysiological, neuropsychological, behavioral, and daily life functioning. Studies are also needed to evaluate the validity and utility of SCT as a transdiagnostic and dimensional construct. In considering SCT as a dimensional and potentially transdiagnostic construct, we describe ways in which SCT might be examined within the RDoC framework, including negative valence systems, cognitive systems, and arousal/regulatory systems, as well as within hierarchical models of psychopathology. Conceptualizing SCT within both categorical and dimensional models of psychopathology will help to better understand the causes, developmental pathways, and clinical implications of SCT, both as a construct in its own right and also in relation to other psychopathologies.

Social anxiety disorder: looking back and moving forward.

Fifty years have passed since social anxiety disorder (SAD) was first differentiated from other phobias. In the years since research has largely aligned with the zeitgeist of categorical classificatory frameworks, and has spanned identifying causes, maintenance factors and innovative interventions. Despite significant advances in the field, the capacity to conceptualise SAD as an independent entity is limited given the heterogeneity and dimensionality of diagnostic criteria, high rates of comorbidity, and non-specificity of aetiological mechanisms, maintaining factors and approaches to treatment. The Research Domain Criteria (RDoC) initiative was developed in an effort to overcome the inherent limitations posed by descriptive diagnostic systems - particularly in terms of reliability and validity - and in doing so seeks to facilitate research into underlying pathophysiological and behavioural mechanisms that cut across traditional diagnostic boundaries. The RDoC framework is furnished with a 'matrix', which in essence corresponds to a set of research principles that attempt to reconcile neuroscience and psychopathology. This review outlines a rationale for integrating SAD research with the RDoC approach, and offers examples of how future studies may wish to frame hypotheses and design experiments as the field moves towards classifying dimensions of psychopathology through a mechanistic understanding of underlying neurobiological and behavioural processes.

The research domain criteria framework in drug discovery for neuropsychiatric diseases: focus on negative valence.

Drug discovery, particularly in the field of central nervous system, has had very limited success in the last few decades. A likely contributor is the poor translation between preclinical and clinical phases. The Research Domain Criteria of the National Institutes of Mental Health is a framework which aims to identify new ways of classifying mental illnesses that are based on observable behaviour and neurobiological measures, and to provide a guiding and evolving framework to improve the translation from preclinical to clinical research. At the core of the Research Domain Criteria approach is the assumption that the dimensional constructs described can be assessed across different units of analysis, thus enabling a more precise quantitative understanding of their neurobiological underpinnings, increasing the likelihood of identifying new and effective therapeutic approaches. In the present review, we discuss how the Research Domain Criteria can be applied to drug discovery with the domain Negative Valence, construct Potential Threat (‘Anxiety’) as an example. We will discuss the evidence supporting the utility of the Research Domain Criteria approach and evaluate how close we are to achieving a common thread of translational research from gene to self-report.

Using the research domain criteria framework to track domains of change in comorbid PTSD and SUD.

Comorbidity in diagnosis raises critical challenges for psychological assessment and treatment. The Research Domain Criteria (RDoC) Project, launched by the National Institutes of Mental Health, proposes domains of functioning as a way to conceptualize the overlap between comorbid conditions and inform treatment selection. However, further research is needed to understand common comorbidities (e.g., posttraumatic stress disorder [PTSD] and substance use disorder [SUD]) from an RDoC framework and how existing evidence-based treatments would be expected to promote change in the RDoC domains of functioning. To address these gaps, the current study examined change in 3 RDoC domains (Negative Valence Systems, Arousal/Regulatory Systems, and Cognitive Systems) during concurrent prolonged exposure (PE) and substance use treatment. Participants were 85 individuals with co-occurring PTSD and SUD who received PE in a residential substance use treatment facility. They completed an experimental task to assess physiological reactivity to trauma and alcohol cues at pre- and posttreatment. Results showed decreased severity in all 3 RDoC domains of interest across the study period. Pairwise comparisons between domains revealed that Arousal/Regulatory Systems had the lowest severity at posttreatment. Subsequent hierarchical linear regression analyses showed that posttreatment domain scores were associated with posttreatment cue reactivity for trauma and alcohol cues. The findings provide preliminary evidence of how the RDoC domains of functioning may change with evidence-based treatments and are discussed in terms of the assessment and treatment of mental health problems using the RDoC framework. (PsycINFO Database Record

Understanding suicide risk within the Research Domain Criteria (RDoC) framework: A meta-analytic review.

The field is in need of novel and transdiagnostic risk factors for suicide. The National Institute of Mental Health's Research Domain Criteria (RDoC) provides a framework that may help advance research on suicidal behavior. We conducted a meta-analytic review of existing prospective risk and protective factors for suicidal thoughts and behaviors (ideation, attempts, and deaths) that fall within one of the five RDoC domains or relate to a prominent suicide theory. Predictors were selected from a database of 4,082 prospective risk and protective factors for suicide outcomes. A total of 460 predictors met inclusion criteria for this meta-analytic review and most examined risk (vs. protective) factors for suicidal thoughts and behaviors. The overall effect of risk factors was statistically significant, but relatively small, in predicting suicide ideation (weighted mean odds ratio: wOR=1.72; 95% CI: 1.59-1.87), suicide attempt (wOR=1.66 [1.57-1.76), and suicide death (wOR=1.41 [1.24-1.60]). Across all suicide outcomes, most risk factors related to the Negative Valence Systems domain, although effect sizes were of similar magnitude across RDoC domains. This study demonstrated that the RDoC framework provides a novel and promising approach to suicide research; however, relatively few studies of suicidal behavior fit within this framework. Future studies must go beyond the "usual suspects" of suicide risk factors (e.g., mental disorders, sociodemographics) to understand the processes that combine to lead to this deadly outcome.

Increasing Traction for Discovery: The Research Domain Criteria Framework and Neurodevelopmental Disorders

Increasing Traction for Discovery: The Research Domain Criteria Framework and Neurodevelopmental Disorders

The history of generalized anxiety disorder as a diagnostic category

From the 19th century into the 20th century, the terms used to diagnose generalized anxiety included "pantophobia" and "anxiety neurosis." Such terms designated paroxysmal manifestations (panic attacks) as well as interparoxysmal phenomenology (the apprehensive mental state). Also, generalized anxiety was considered one of numerous symptoms of neurasthenia, a vaguely defined illness. Generalized anxiety disorder (GAD) appeared as a diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980, when anxiety neurosis was split into GAD and panic disorder. The distinct responses these two disorders had to imipramine therapy was one reason to distinguish between the two. Since the revised DSM-III (DSM-III-R), worry about a number of life circumstances has been gradually emphasized as the distinctive symptom of GAD. Thus, a cognitive aspect of anxiety has become the core criterion of GAD. The validity of GAD as an independent category has been questioned from DSM-III up to preparation of DSM-5. Areas of concern have included the difficulty to establish clear boundaries between GAD and (i) personality dimensions, (ii) other anxiety-spectrum disorders, and (iii) nonbipolar depression. The National Institute of Mental Health has recently proposed the Research Domain Criteria (RDoC), a framework destined to facilitate biological research into the etiology of mental symptoms. Within the RDoC framework, generalized anxiety might be studied as a dimension denominated "anxious apprehension" that would typically fit into the research domain called "negative valence systems" and the more specific construct termed "potential threat."

Utilizing a transdiagnostic neuroscience-informed approach to differentiate the components of a complex clinical presentation: A case report

BackgroundRecent research recognizes considerable overlap in the clinical presentation of psychiatric disorders such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder and Social Anxiety Disorder. The diagnostic approach collects symptoms to reflect a single underlying psychopathological process. The Research Domain Criteria (RDoC) emphasizes psychopathology as arising from combinations of abnormalities in core underlying constructs that can be measured at many levels of analysis, from biological to behavioral. Patients who present with clinical heterogeneity may benefit from transdiagnostic case conceptualization that integrates detailed symptom information across multiple measurements spanning multiple domains of functioning based in the RDoC framework. Case presentationWe report on one case that was included in a research study focused on advancing knowledge towards a transdiagnostic, brain-based model of anxiety and depression. The 20-year-old male patient presented at a community mental health clinic for inattention, low mood, sleep problems and anxious symptoms. The patient also presented with primary problems in negative valence systems (anxiety, avoidance, and bias towards negative information), cognitive systems (fluctuating cognitive ability over time, poor concentration and ability to focus), and social processing systems (deficits in social communication skills). Conceptualizing this case through a transdiagnostic lens augmented the patient’s treatment plan by including a more integrative approach. Treatment included social skills training, progressive relaxation exercises, and basic psychoeducation in emotional expression and independent living skills. ConclusionThis case illustrates the utility of a transdiagnostic approach, particularly when a traditional diagnostic model generates conflicting evidence and/or multiple comorbidities. RDoC provides a framework for integrating abnormalities across multiple dimensions. Furthermore, it lays the foundation for future integration of brain-behavior relationships into case conceptualization and personalized treatment approaches.

Understanding Suicide Risk within the Research Domain Criteria (RDoC) Framework: Insights, Challenges, and Future Research Considerations.

Suicide is a leading cause of death worldwide. Prior research has focused primarily on sociodemographic and psychiatric risk factors with little improvement in the prediction or prevention of suicidal behavior over time. The Research Domain Criteria (RDoC) may be an especially useful framework for advancing research in this area. This paper provides a brief and broad overview of research on suicidal behavior relating to each of the RDoC domains-highlighting the RDoC construct(s) where research has focused, construct(s) where research is lacking, and suggestions for future research directions. We also discuss major challenges for suicide research within the RDoC framework, including the intersection of RDoC domains, interaction of domains with the environment, incorporation of developmental stage, integration of distal and proximal processes, and inclusion of suicide-specific constructs. We conclude by underscoring important considerations for future research aimed at using the RDoC framework to study suicidal behavior and other forms of psychopathology.

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.

The Research Domain Criteria framework: transitioning from dimensional systems to integrating neuroscience and psychopathology

ABSTRACTAlthough recent research in neuroscience and genetics is providing new insights into the etiology of psychiatric disorders, progress in treatment development has been hindered by reliance on diagnostic categories that are based primarily on presenting signs and symptoms. The NIMH Research Domain Criteria (RDoC) framework seeks to provide a neuroscience-based nosological background for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that benefit from significant progress in modern neuroscience. These scientific advances combined with new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatments available. In this editorial, we describe the RDoC framework compared with Diagnostic and Statistical Manual/International Classification of Disease systems and highlight some of the emerging progress in RDoC-based research that is consistent with these developments.

Supplemental Material for Using the Research Domain Criteria Framework to Track Domains of Change in Comorbid PTSD and SUD

Supplemental Material for Using the Research Domain Criteria Framework to Track Domains of Change in Comorbid PTSD and SUD

Connecting psychopathology meta-structure and mechanisms.

A persistent challenge for the field of psychopathology has been how to best explain mental disorders and organize clinical symptoms into diagnoses. Meta-structural approaches have clarified fundamental problems and made substantial gains by using covariance structures to organize the nature of clinical symptom patterns. A remaining task is how to specify the connections between these patterns across behavioral, cognitive, and neural mechanisms. Together, meta-structural approaches and the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) offer a means to parse out these connections. I comment on the included articles in this special section on psychopathology meta-structure and argue that core dimensions of psychopathology identified with meta-structural approaches can advance the RDoC initiative and that the RDoC framework, in turn, can strengthen structural approaches by providing an organizational scaffold to elucidate the relations of behavioral, cognitive, and neural mechanisms and to relate them to dimensions of human suffering and dysfunction. (PsycINFO Database Record

Using the Research Domain Criteria Framework to Explore Associations Between MMPI–2–RF Constructs and Physiological Variables Assessed by Eye-Tracker Technology

ABSTRACTThe National Institute of Mental Health has proposed a paradigm shift in the conceptualization of psychopathology, abandoning the traditional categorical model in favor of one based on hierarchically organized dimensional constructs (Insel et al., 2010). One explicit goal of this initiative, the Research Domain Criteria (RDoC) project, is to facilitate the incorporation of newly available neurobiologic variables into research on psychopathology. The Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI–2–RF; Ben-Porath & Tellegen, 2008/2011) represents a similar paradigm shift, also adopting a hierarchical arrangement of dimensional constructs. This study examined associations between MMPI–2–RF measures of psychopathology and eye-movement metrics. Participants were college students (n = 270) who completed the MMPI–2–RF and then viewed a sequence of 30-s video clips. Results show a pattern of positive correlations between pupil size and emotional/internalizing dysfunction scales when viewing video eliciting negative emotional reactions, reflecting greater arousability in individuals with higher scores on these measures. In contrast, when viewing stimuli depicting angry, threatening material, a clear pattern of negative correlations was found between pupil size and behavioral/externalizing trait measures. These data add to the construct validity of the MMPI–2–RF and support the use of the RDoC matrix as a framework for research on psychopathology.

Using a cultural and RDoC framework to conceptualize anxiety in Asian Americans

Asian Americans are one of the fastest growing minority groups in the United States; however, mental health within this population segment, particularly anxiety disorders, remains significantly understudied. Both the heterogeneity within the Asian American population and the multidimensional nature of anxiety contribute to difficulties in understanding anxiety in this population. The present paper reviewed two sources of heterogeneity within anxiety in Asian Americans: (1) cultural variables and (2) mechanisms or components of anxiety. Specifically, we examined four cultural variables most commonly found in research related to anxiety in Asian Americans: acculturation, loss of face, affect valuation, and individualism-collectivism. We also discussed ways to parse anxiety through a Research Domain Criteria (RDoC) framework, specifically focusing on sensitivity to acute and potential threat, constructs within the Negative Valence System. Previously unpublished preliminary data were presented to illustrate one way of examining ethnic differences in anxiety using an RDoC framework. Finally, this paper offered recommendations for future work in this area.

Engaging Research Domain Criteria (RDoC): Neurocircuitry in Search of Meaning.

The Research Domain Criteria (RDoC) initiative was implemented to reorient the approach to mental health research from one focused on Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology to one oriented to psychological constructs constrained by neurocircuitry and molecular entities. The initiative has generated significant discussion and valuable reflection on the moorings of psychiatric research. The purpose of this article is to illustrate how a basic or clinical investigator can engage RDoC to explore the neurobiological underpinnings of psychopathology and how a research question can be formulated in RDoC's framework. We utilize a brain region with significant growing interest, the habenula, as an example for probing RDoC's utility. Opportunities to enhance neurocircuitry-psychological construct associations and problems associated with neuronal populations that enable bidirectional circuitry influence are discussed. The exercise reveals areas for further development that could move RDoC from a promising research idea to a successfully engaged foundation for catalyzing clinically relevant discoveries.