Research Domain Criteria Framework Research Articles

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.

RDoC and shift of reference

This paper aims to analyse in a philosophically informed way the recent National Institute of Mental Health proposal for the Research Domain Criteria (RDoC) framework. Current classification systems have helped unify psychiatry and the conditions that it is most concerned with. However, by relying too much on syndromes and symptoms, they too often do not define stable constructs. As a result, inclusions and removals from the manuals are not always backed by sound reasons. The RDoC framework is an important move towards ameliorating matters. This paper argues that it improves the current situation by re-referencing constructs to physical properties (biomarkers for disorders, for example), by allowing theoretical levels within the framework, and by treating psychiatry as a special case of the cognitive sciences.

Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation.

The term “eating disorders” (ED) encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS). NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related to rewards and punishment, cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC) initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and the underlying behavioral and neurobiological targets associated with ED. This review will also identify candidate targets for NIBS based on these dimensions and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED.

Displacement behaviors in chimpanzees (Pan troglodytes): A neurogenomics investigation of the RDoC Negative Valence Systems domain.

The current study aimed to systematically investigate genetic and neuroanatomical correlates of individual variation in scratching behaviors, a well-validated animal-behavioral indicator of negative emotional states with clear links to the NIMH Research Domain Criteria (RDoC) response to potential harm ("anxiety") construct within the Negative Valence Systems domain. Utilizing data from a sample of 76 captive chimpanzees (Pan troglodytes), we (a) examined the association between scratching and presence or absence of the RS3-containing DupB element in the AVPR1A 5' flanking region, (b) utilized voxel-based morphometry (VBM) to identify gray matter (GM) voxel clusters that differentiated AVPR1A genotype, and (c) conducted a VBM-guided voxel-of-interest analysis to examine the association between GM intensity and scratching. AVPR1A evidenced sexually dimorphic associations with scratching. VBM analyses revealed significant differences in GM by genotype across twelve clusters largely in the frontal cortex. Regions differentiating AVPR1A genotype showed sex-specific associations with scratching. Results suggest that sexually dimorphic associations between AVPR1A and scratching may be explained by genotype-specific neuroanatomical variation. The current study provides an example of the way in which chimpanzee research is uniquely poised for multilevel, systematic investigations of psychopathology-relevant constructs within the context of the RDoC framework.

Reshaping clinical science: Introduction to the Special Issue on Psychophysiology and the NIMH Research Domain Criteria (RDoC) initiative.

The National Institute of Mental Health's (NIMH) Research Domain Criteria (RDoC) initiative seeks to establish new dimensional conceptions of mental health problems, through the investigation of clinically relevant "process" constructs that have neurobiological as well as psychological referents. This special issue provides a detailed overview of the RDoC framework by NIMH officials Michael Kozak and Bruce Cuthbert, and spotlights RDoC-oriented investigative efforts by leading psychophysiological research groups as examples of how clinical science might be reshaped through application of RDoC principles. Accompanying commentaries highlight key aspects of the work by each group, and discuss reported methods/findings in relation to promises and challenges of the RDoC initiative more broadly.

Subjective Response to Alcohol as a Research Domain Criterion.

Individual differences in the subjective experience of the pharmacological effects of alcohol have long been implicated in the likelihood that one will drink heavily and develop alcoholism. The theme of this conceptual review and perspective article is to synthesize the literature on subjective responses to alcohol and to set an agenda for the next generation of research in the area. Specifically, we contend that in order for subjective response to alcohol to play a prominent role in alcoholism research, it is critical that it be studied as a multimodal phenotype. First, we review the human research on subjective response to alcohol measured under controlled laboratory conditions and draw recommendations for the application of these findings to understanding alcoholism neurobiology in humans. Second, we highlight multimodal approaches, including studies of the genetic and neural substrates of individual differences in subjective response to alcohol. Third, we review treatment implications with a focus on subjective response to alcohol as an intervention target. Upon review of the research on subjective response to alcohol across levels of analyses, we provide recommendations for leveraging these phenotypes in a systematic and methodologically rigorous fashion that can address central questions about alcoholism etiology, disease progression, and personalized treatment. The approach recommended herein is largely consistent with the Research Domain Criteria (RDoC) initiative across the National Institute of Mental Health. The defining feature of such domains is that they inform behavior yet be amenable to examination through multiple units of analysis, such as molecular, genetic, circuit-level, and behavioral measurements. To that end, we contend that subjective response to alcohol represents a behaviorally and biologically plausible phenotype upon which to build using the RDoC framework for understanding alcohol use disorder.

Is the Divide a Chasm?: Bridging Affective Science with Clinical Practice.

This special section endeavors to facilitate the integration of biologically-based assessments of emotion into the clinical setting. This goal is consistent with the Research Domain Criteria (RDoC) initiative, which aims to identify transdiagnostic biobehavioral mechanisms that underlie mental disorders. We focus on four challenges to applying biologically-informed research on emotion and emotion regulation to clinical contexts: (1) How do we assess emotion in an RDoC framework? (2) How do we integrate measures of emotion with other systems in a wider context? (3) What do physiological indices of emotion tell us about clinical phenomena? and (4) How do we integrate physiological assessments into clinical practice? Throughout this comment, we refer to the articles in this special section to make our points, and, when possible, offer suggestions for future work to continue to address these challenges.