Mental Health Research Domain Research Articles

Morbid Anxiety: Identification and Treatment.

Due to their prevalence, chronicity, and poorly understood pathophysiology, anxiety disorders remain an important public health problem. Despite clear diagnostic guidelines and the availability of excellent evidence-based treatments, most anxiety patients remain underrecognized and inadequately treated. This clinical synthesis highlights changes to anxiety disorder diagnosis that became effective with DSM-5. The article also provides some clinical perspective on clarifying differential diagnostic problems and building an alliance with the anxious patient. The quality and strength of the evidence base for current anxiolytic medications options (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, benzodiazepines, and other agents), antianxiety psychotherapies (cognitive-behavioral therapy and brief dynamic therapies), and combination treatments are discussed. A brief update on newer treatment strategies, such as cognitive enhancement, complementary therapies, and neuromodulation, is included. Future directions for anxiety nosology and treatment are summarized, including the National Institute of Mental Health Research Domain Criteria initiative and the promising role of personalized medicine.

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: "Training for Awareness Resilience and Action" (TARA)-A Pilot Study.

The novel group treatment program Training for Awareness, Resilience, and Action (TARA) was developed to target specific mechanisms based on neuroscience findings in adolescent depression and framed within the National Institute of Mental Health Research Domain Criteria. TARA contains training of autonomic and emotional self-regulation, interoceptive awareness, relational skills, and value-based committed action. We performed a single-arm trial to test the feasibility and preliminary efficacy of TARA in reducing depression and anxiety levels and assessed whether the specific targeted domains of function reflected the hypothesized symptom change. Twenty-six adolescents (14-18 years old, 7 males and 19 females) participated in the 12-week group program. Assessment was performed before (T0), immediately after (T1), and 3 months after the end of TARA (T2). Significant improvement was seen in depression symptoms (Reynolds Adolescent Depression Scale Second Edition) between T0-T1 (t-value = -3.56, p = 0.002, CI = -6.64, -1.77) and T0-T2 (t-value = -4.17, p < 0.001, CI = -11.20, -3.75) and anxiety symptoms (Multidimensional Anxiety Scale for Children) between T0-T1 (t-value = -2.26, p = 0.033, CI = -4.61, -0.21) and T0-T2 (t-value = -3.06, p = 0.006, 95% confidence interval = -9.02, -1.73). Significant improvements in psychological flexibility, sleep, and mindfulness skills were also found between T0 and T2. The sample size was small without a control condition. The pilot design did not allow for testing the hypothesized brain changes and effect of TARA on relevant systemic biomarkers. TARA is feasible in a sample of clinically depressed and/or anxious adolescents and preliminary efficacy was demonstrated by reduced depression and anxiety symptoms. The specific symptom and behavioral outcomes corresponded well with the hypothesized mechanisms of change.

Biological Aging and the Future of Geriatric Psychiatry.

Advances in understanding the biological bases of aging have intellectually revitalized the field of geriatric psychiatry and broadened its scope to include promoting successful aging and studying resilience factors in older adults. To describe the process by which this paradigm shift has occurred and illustrate its implications for treatment and research of late-life brain disorders, late-life depression is discussed as a prototype case. Prior phases of geriatric psychiatry research were focused on achieving depressive symptom relief, outlining pharmacokinetic and pharmacodynamic differences between older and younger adults, and identifying moderators of treatment response. Building on this work, current geriatric psychiatry researchers have begun to disentangle the etiologic complexity in late-life depression by focusing on the causative aging-related processes involved, identifying both neurobiological and behavioral intermediates, and finally delineating depression subtypes that are distinguishable by their underlying biology and the treatment approach required. In this review, we discuss several age-related processes that are critical to the development of late-life mood disorders, outline implications of these processes for the clinical evaluation and management of later-life psychiatric disorders, and finally put forth suggestions for better integrating aging and developmental processes into the National Institute of Mental Health's Research Domain Criteria.

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

Is Poor Working Memory a Transdiagnostic Risk Factor for Psychopathology?

In contrast to historical conceptualizations that framed psychological disorders as distinct, categorical conditions, it is now widely understood that co- and multi-morbidities between disorders are extensive. As a result, there has been a call to better understand the dimensional liabilities that are common to and influence the development of multiple psychopathologies, as supported and exemplified by the National Institutes of Mental Health (NIMH) Research Domain Criteria (RDoC) framework. We use a latent variable SEM approach to examine the degree to which working memory deficits represent a cognitive liability associated with the development of common and discrete dimensions of psychopathology. In a sample of 415 community recruited children aged 8-12 (n=170 girls), we fit a bi-factor model to parent reports of behavior from the DISC-4 and BASC-2, and included a latent working memory factor as a predictor of the internalizing, externalizing, and general "p-factor." We found that both the general "p-factor" and externalizing (but not internalizing) latent factor were significantly associated with working memory. When a bi-factor model of externalizing symptomology was fit to further explore this relationship, working memory was only correlated with the general externalizing dimension; correlation with specific inattention, hyperactive/impulsive, and oppositional factors did not survive once the general externalizing dimension was taken into consideration. These findings held regardless of the sex of the child. Our results suggest that working memory deficits represent both a common cognitive liability for mental health disorders, and a specific liability for externalizing disorders.

"Unreliability as a threat to understanding psychopathology: The cautionary tale of attentional bias": Correction to Rodebaugh et al. (2016).

Reports an error in "Unreliability as a threat to understanding psychopathology: The cautionary tale of attentional bias" by Thomas L. Rodebaugh, Rachel B. Scullin, Julia K. Langer, David J. Dixon, Jonathan D. Huppert, Amit Bernstein, Ariel Zvielli and Eric J. Lenze (Journal of Abnormal Psychology, 2016[Aug], Vol 125[6], 840-851). There was an error in the Author Note concerning the support of the MacBrain Face Stimulus Set. The correct statement is provided. (The following abstract of the original article appeared in record 2016-30117-001.) The use of unreliable measures constitutes a threat to our understanding of psychopathology, because advancement of science using both behavioral and biologically oriented measures can only be certain if such measurements are reliable. Two pillars of the National Institute of Mental Health's portfolio-the Research Domain Criteria (RDoC) initiative for psychopathology and the target engagement initiative in clinical trials-cannot succeed without measures that possess the high reliability necessary for tests involving mediation and selection based on individual differences. We focus on the historical lack of reliability of attentional bias measures as an illustration of how reliability can pose a threat to our understanding. Our own data replicate previous findings of poor reliability for traditionally used scores, which suggests a serious problem with the ability to test theories regarding attentional bias. This lack of reliability may also suggest problems with the assumption (in both theory and the formula for the scores) that attentional bias is consistent and stable across time. In contrast, measures accounting for attention as a dynamic process in time show good reliability in our data. The field is sorely in need of research reporting findings and reliability for attentional bias scores using multiple methods, including those focusing on dynamic processes over time. We urge researchers to test and report reliability of all measures, considering findings of low reliability not just as a nuisance but as an opportunity to modify and improve upon the underlying theory. Full assessment of reliability of measures will maximize the possibility that RDoC (and psychological science more generally) will succeed. (PsycINFO Database Record

Updating the Research Domain Criteria

Two and a half years ago, World Psychiatry published a Forum about the US National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) initiative1. In it, there was spirited commentary with divergent views of diagnosis and critical examination of RDoC. Some criticisms were based on an incomplete understanding of RDoC2, but the discussion captured the challenge of shifting the paradigm for psychiatric nosology. Here I provide an update on RDoC, while articulating some fundamental issues.

Empirically derived patterns of psychiatric symptoms in youth: A latent profile analysis

BackgroundBy conceptualizing domains of behavior transdiagnostically, the National Institute of Mental Health Research Domain Criteria (NIMH RDoC) initiative facilitates new ways of studying psychiatric symptoms. In this study, latent profile analysis (LPA) was used to empirically derive classes or patterns of psychiatric symptoms in youth that transect traditional nosologic boundaries. MethodsData were drawn from 509 children and adolescents (ages 7-18 years; mean age =12.9 years; 54% male) who were evaluated in the NIMH Emotion and Development Branch and were heterogeneous with respect to presenting diagnoses and symptoms. Youth and/or their parents completed measures of several core symptom dimensions: irritability, anxiety, depression, and attention deficit hyperactivity disorder (ADHD). LPA was used to parse response patterns into distinct classes, based on the levels of, and interrelations among, scores on the different measures. ResultsFive classes emerged: low levels of symptomatology (52% of sample); anxiety and mild depressive symptoms (17%); parent-reported irritability and ADHD (16%); irritability and mixed comorbid symptoms (10%); and high levels of irritability, anxiety, depression, and ADHD (5%). Importantly, these latent classes cut across informants and the clinical conditions for which youth were initially evaluated. Further, the classes characterized by irritability exhibited the poorest overall functioning. LimitationsThese data were cross-sectional. Examination of external validators, including neurobiological correlates and symptom course, is warranted. ConclusionsResults inform our understanding of the structure of psychiatric symptoms in youth and suggest new ways to operationalize psychopathology and examine it in relation to neurobiology.

Gain in Translation: Is It Time for Thigmotaxis Studies in Humans?

Gain in Translation: Is It Time for Thigmotaxis Studies in Humans?

Unreliability as a threat to understanding psychopathology: The cautionary tale of attentional bias.

The use of unreliable measures constitutes a threat to our understanding of psychopathology, because advancement of science using both behavioral and biologically oriented measures can only be certain if such measurements are reliable. Two pillars of the National Institute of Mental Health's portfolio-the Research Domain Criteria (RDoC) initiative for psychopathology and the target engagement initiative in clinical trials-cannot succeed without measures that possess the high reliability necessary for tests involving mediation and selection based on individual differences. We focus on the historical lack of reliability of attentional bias measures as an illustration of how reliability can pose a threat to our understanding. Our own data replicate previous findings of poor reliability for traditionally used scores, which suggests a serious problem with the ability to test theories regarding attentional bias. This lack of reliability may also suggest problems with the assumption (in both theory and the formula for the scores) that attentional bias is consistent and stable across time. In contrast, measures accounting for attention as a dynamic process in time show good reliability in our data. The field is sorely in need of research reporting findings and reliability for attentional bias scores using multiple methods, including those focusing on dynamic processes over time. We urge researchers to test and report reliability of all measures, considering findings of low reliability not just as a nuisance but as an opportunity to modify and improve upon the underlying theory. Full assessment of reliability of measures will maximize the possibility that RDoC (and psychological science more generally) will succeed. (PsycINFO Database Record

Editorial: Frontiers in Brain-Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry

The Editorial on the Research Topic Frontiers in Brain-Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry Childhood psychiatric disorders present challenges given the heterogeneity of presentations, instability of phenotypes, and nascent understanding of neurodevelopment. Recent efforts, such as the National Institute of Mental Health Research Domain Criteria, aim to hone precision medicine approaches for psychiatric disorders (1). Elucidating the ontogeny of psychiatric illnesses and underlying neurobiology is a mandate for advancing modern clinical practice. Recent advances in neuroimaging, preclinical studies, genomics, and non-invasive brain stimulation may soon provide improved monitoring of development in health and disease. These tools also hold great promise for developing biological markers of illness that may be targeted through treatment innovation. This research topic surveys recent developmentally informed clinical neuroscience efforts focused on conditions that affect children and adolescents. Broadly, this includes studies focusing on neurodevelopmental disorders, eating disorders, mood disorders, and treatment innovations.

Award for distinguished contributions to psychophysiology: Gregory A. Miller.

Award for distinguished contributions to psychophysiology: Gregory A. Miller.

An examination of the language construct in NIMH's research domain criteria: Time for reconceptualization!

The National Institute of Mental Health's Research Domain Criteria (RDoC) Initiative “calls for the development of new ways of classifying psychopathology based on dimensions of observable behavior.” As a result of this ambitious initiative, language has been identified as an independent construct in the RDoC matrix. In this article, we frame language within an evolutionary and neuropsychological context and discuss some of the limitations to the current measurements of language. Findings from genomics and the neuroimaging of performance during language tasks are discussed in relation to serious mental illness and within the context of caveats regarding measuring language. Indeed, the data collection and analysis methods employed to assay language have been both aided and constrained by the available technologies, methodologies, and conceptual definitions. Consequently, different fields of language research show inconsistent definitions of language that have become increasingly broad over time. Individually, they have also shown significant improvements in conceptual resolution, as well as in experimental and analytic techniques. More recently, language research has embraced collaborations across disciplines, notably neuroscience, cognitive science, and computational linguistics and has ultimately re‐defined classical ideas of language. As we move forward, the new models of language with their remarkably multifaceted constructs force a re‐examination of the NIMH RDoC conceptualization of language and thus the neuroscience and genetics underlying this concept. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Psychoneurometric operationalization of threat sensitivity: Relations with clinical symptom and physiological response criteria.

The National Institute of Mental Health's Research Domain Criteria (RDoC) initiative calls for the incorporation of neurobiological approaches and findings into conceptions of mental health problems through a focus on biobehavioral constructs investigated across multiple domains of measurement (units of analysis). Although the constructs in the RDoC system are characterized in "process terms" (i.e., as functional concepts with brain and behavioral referents), these constructs can also be framed as dispositions (i.e., as dimensions of variation in biobehavioral functioning across individuals). Focusing on one key RDoC construct, acute threat or "fear," the current article illustrates a construct-oriented psychoneurometric strategy for operationalizing this construct in individual difference terms-as threat sensitivity (THT+). Utilizing data from 454 adult participants, we demonstrate empirically that (a) a scale measure of THT+ designed to tap general fear/fearlessness predicts effectively to relevant clinical problems (i.e., fear disorder symptoms), (b) this scale measure shows reliable associations with physiological indices of acute reactivity to aversive visual stimuli, and (c) a cross-domain factor reflecting the intersection of scale and physiological indicators of THT+ predicts effectively to both clinical and neurophysiological criterion measures. Results illustrate how the psychoneurometric approach can be used to create a dimensional index of a biobehavioral trait construct, in this case THT+, which can serve as a bridge between phenomena in domains of psychopathology and neurobiology. Implications and future directions are discussed with reference to the RDoC initiative and existing report-based conceptions of psychological traits.

The NIMH Research Domain Criteria Initiative: Background, Issues, and Pragmatics.

This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct "grain size," and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design.

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.

The error-related negativity: A transdiagnostic marker of sustained threat?

The creation of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) project has been the driving force behind the reconceptualization of the pathogenesis of psychiatric disorders. In this commentary, I explore whether the error-related negativity can be considered as a transdiagnostic marker of sustained threat based on findings from Weinberg, Meyer et al.'s (2016) study in relation to current findings in the literature. Potential alternative study designs, use of a multimodal approach to the assessment of a specific phenotype of clinical phenomenon, and the importance of integrating a neurodevelopmental perspective are also discussed.

We need science to be useful too.

We need science to be useful too.

Variation and validation: the example of schizophrenia.

Variation and validation: the example of schizophrenia.

Alternative Perspectives on Psychiatric Validation

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.The assumptions and aspirations of psychiatric nosology have been pushed to the fore by the National Institute of Mental Health Research Domain Criteria (RDoC) initiative and American Psychiatric Association's release of the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM-5). These 2 systems for conceptualizing psychopathology hint at the diversity of possible systems. DSM-5 remains a tool for operationalizing symptomatically defined categories; it offers potential solutions to the problems of caseness and the enumeration of clinically relevant features.