Research Domain Criteria Research Articles

The domain "social processes" in the system of research domain criteria: current state and perspectives

Soziale Prozesse und ihre Störungen, z. B. bei Autismusspektrumstörungen und psychotischen Störungen, sind seit jeher zentral für das Fach Psychiatrie. Die letzten Jahrzehnte haben zu beeindruckenden Fortschritten in unserem Verständnis der zugrunde liegenden neurobiologischen Grundlagen geführt, aber auch in der Art und Weise, wie wir soziale Prozesse untersuchen und analysieren. Seit ihrer Einführung bieten die Research Domain Criteria ein leistungsstarkes Rahmenwerk für die Operationalisierung und Unterteilung komplexer sozialer Prozesse in einer Weise, die sowohl neurobiologisch orientierte als auch klinische Ansätze zulässt. In diesem Artikel fassen wir die wichtigsten Erkenntnisse für jedes der vier grundlegenden Konstrukte der Domäne sozialer Prozesse zusammen und diskutieren sie: (a) Zugehörigkeit und Bindung, (b) soziale Kommunikation, (c) Wahrnehmung und Verständnis des Selbst und (d) Wahrnehmung und Verständnis anderer. Dabei heben wir insbesondere die klinische Relevanz der Erkenntnisse hervor, die auf dem Gebiet der sozialen Neurowissenschaften gewonnen wurden, und diskutieren die daraus resultierende zunehmende Bedeutung transdiagnostischer Konzepte in der angewandten Forschung. Schließlich stellen wir drei innovative Forschungsmethoden vor, die auf den sich beschleunigenden technologischen Fortschritten des letzten Jahrzehnts aufbauen und es zunehmend ermöglichen, komplexe soziale Interaktionen auch unter realistischeren und alltagsnäheren Bedingungen zu untersuchen.

Mapping of Transdiagnostic Neuropsychiatric Phenotypes Across Patients in Two General Hospitals.

Multidimensional transdiagnostic phenotyping systems are increasingly important to neuropsychiatric phenotyping, particularly in translational research settings. The relationship the National Institute of Mental Health's Research Domain Criteria multidimensional approach to psychopathology and nonpsychiatric diagnoses has not been studied at scale but is relevant to those caring for neuropsychiatric illness in medical and surgical settings. We applied the CQH Dimensional Phenotyper natural language processing tool to estimate National Institute of Mental Health's Research Domain Criteria domain-associated symptoms of individuals admitted to nonpsychiatric wards at each of 2 large academic general hospitals over an 8-year period. We compared patterns in individual domain symptom burden, as well as a new pooled unidimensional measure, by primary medical and surgical diagnosis. Analysis included 227,243 patients from hospital 1 of whom 68,793 (30.3%) had a prior psychiatric history and 220,213 patients from hospital 2 of whom 50,818 (23.1%) had a prior psychiatric history. The distribution of Research Domain Criteria symptom burdens over primary diagnosis was similar across hospital sites and differed significantly across primary medical or surgical diagnosis. The effect of primary medical or surgical diagnosis was larger than that of prior psychiatric history on Research Domain Criteria symptom burden. Research Domain Criteria-based neuropsychiatric symptom burden estimated from general hospital patients' clinical documentation is more strongly associated with the primary hospital medical or surgical diagnosis than it is with the presence of a previous psychiatric history. The bidirectional role of psychiatric and somatic illness warrants further study through the lens of transdiagnostic phenotyping.

Fine-Tuning the PI3K/Akt Signaling Pathway Intensity by Sex and Genotype-Load: Sex-Dependent Homozygotic Threshold for Somatic Growth but Feminization of Anxious Phenotype in Middle-Aged PDK1 K465E Knock-In and Heterozygous Mice.

According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling, an essential pathway for regulating cellular processes and physiology, and its modulation through aging. Here we describe, for the first time, the in vivo behavioral impact of the sex and genetic-load tweaking this pathway. The anxiety-like phenotypes of 61 mature (11–14-month-old) male and female PDK1 K465E knock-in, heterozygous, and WT mice were studied. Forced (open-field) anxiogenic environmental conditions were sensitive to detect sex and genetic-load differences at middle age. Despite similar neophobia and horizontal activity among the six groups, females exhibited faster ethograms than males, with increased thigmotaxis, increased wall and bizarre rearing. Genotype-load unveiled increased anxiety in males, resembling female performances. The performance of mutants in naturalistic conditions (marble test) was normal. Homozygotic-load was needed for reduced somatic growth only in males. Factor interactions indicated the complex interplay in the elicitation of different negative valence system’s items and the fine-tuning of PI3K/Akt signaling pathway intensity by genotype-load and sex.

Lack of Associations Between C-Reactive Protein and Mood and Anxiety Symptoms in Adolescents.

Introduction: Increased peripheral inflammation has been consistently documented in both adult and pediatric depression. However, elevated levels of C-reactive protein (CRP), a nonspecific biomarker for inflammation, have been primarily reported in adults; whether CRP plays a similar role in adolescent depression has not been conclusively established. In our prior work, we identified relationships between CRP and reward neurocircuitry in adolescents with psychiatric symptoms (N = 64) but not with depressive symptoms. Extending this work, we sought to examine CRP across the full range of mood and anxiety symptom severity in a larger, clinically diverse cohort of psychotropic medication-free adolescents and healthy controls (HCs). Methods: Subjects were adolescents (N = 127, age: 15.17 ± 2.19 years, 78 female) with psychiatric symptoms (n = 96, including previous cohort of 64) and HC (n = 31). All completed a semi-structured psychiatric evaluation and dimensional assessments for depression, anxiety, anhedonia, and suicidality. Group-comparison and correlation analyses utilized nonparametric statistics controlled for body mass index, sex, and age at pFWE < 0.05. Results: No group differences were identified in CRP levels between the clinical cohort and HCs. In addition, correlations between CRP and clinical symptomatology were not significant in either the whole sample or the psychiatric group. Conclusions: We found that, unlike in adults, CRP was not associated with depressive symptoms. This suggests that inflammation in pediatric depression is more narrowly delimited at the onset of psychiatric symptoms and may only become systemic with chronicity.

Assessment of Spaceflight Medical Conditions’ and Treatments’ Potential Impacts on Behavioral Health and Performance

Long-duration space exploration missions will pose significant risks to the physical and behavioral health and performance of the crew. We documented the presence and frequency of (1) behavioral health and performance (BHP)-relevant symptoms for each condition in NASA's Exploration Medical Conditions List (EMCL), (2) the BHP-relevant effects of applicable medical treatments in the current International Space Station (ISS) On-Orbit Medication List, (3) the breadth of potential BHP impacts of spaceflight medical treatments, and (4) the likelihood of adverse BHP effects of treating spaceflight medical conditions. BHP symptoms and effects were categorized by the six neurobehavioral domains of the National Institute of Mental Health's Research Domain Criteria (RDoC) framework. Including the cognitive effects of acute and chronic pain (e.g., attention, memory), 94% of spaceflight medical conditions include symptoms relevant to Cognitive Systems (e.g., attention deficits, confusion, psychosis), 36% include symptoms relevant to Negative Valence Systems (e.g., anxiety), 32% include symptoms relevant to Arousal and Regulatory Systems (e.g., sleep disturbances), 22% include symptoms relevant to Sensorimotor Systems (e.g., dizziness), 19% include symptoms relevant to Positive Valence Systems (e.g., mania), and 11% include symptoms relevant to Social Processes (e.g., social withdrawal). Only 2% of spaceflight medical conditions have no documented BHP symptoms. Of the spaceflight medical treatments, 63% affect Arousal and Regulatory Systems, 60% affect Sensorimotor Systems, 59% affect Cognitive Systems, 53% affect Negative Valence Systems, 38% affect Positive Valence Systems, and 31% affect Social Processes. The breadth of potential BHP impacts was bimodal, in that 27% of spaceflight medical treatments had no documented BHP effects; however, 27% of treatments may produce adverse effects across all six neurobehavioral domains. Historical prevalence data on medical conditions, symptoms, and complaints from 14 years of International Space Station operations coupled with documented BHP effects of recommended treatments indicates the potential for up to 481 adverse BHP effects of spaceflight medical treatments per person-year. Assessing the potential BHP impacts of spaceflight medical conditions and their treatments highlights the interactive nature of operational risks, and can provide an enhanced evidence base to support integrated research and countermeasure development strategies for long-duration exploration missions.

The sensorimotor domain in the research domain criteria system: progress and perspectives

Over the past three decades research interest in hypokinetic, hyperkinetic, sensorimotor and psychomotor abnormalities in mental disorders has steadily increased. This development has led to an increasing number of scientific initiatives that have not only highlighted the clinical need for early detection of extrapyramidal motor symptoms, tardive dyskinesia and catatonia but also provided numerous neurobiological findings and clinically relevant results based on the pathology of the sensorimotor system in patients with mental disorders. In view of these developments in January 2019 the National Institute of Mental Health (NIMH) research domain criteria (RDoC) initiative introduced asixth domain called the sensorimotor domain to address deficits in the sensorimotor system and associated behavioral abnormalities. To draw attention to the rapid progress just since the introduction of the sensorimotor domain, a2-year (1 January 2019-18 February 2021) systematic review is presented highlighting recent neuroimaging findings and discussing challenges for future research. In summary, aberrant sensorimotor processing in mental disorders is associated with dysfunction of the cerebello-thalamo-motor cortex network, which interacts with (social)cognitive and affective systems. Initial longitudinal and interventional studies highlight the translational potential of the sensorimotor domain.

Describing disorder: The importance and advancement of compositional explanations in psychopathology

Understanding the makeup of mental disorders has great value for both research and practice in psychopathology. The richer and more detailed our compositional explanations of mental disorder—that is, comprehensive accounts of client signs and symptoms—the more information we have to inform etiological explanations, classification schemes, clinical assessment, and treatment. However, at present, no explicit compositional explanations of psychopathology have been developed and the existing descriptive accounts that could conceivably fill this role—DSM/ICD syndromes, transdiagnostic and dimensional approaches, symptom network models, historical accounts, case narratives, and the Research Domain Criteria (RDoC)—fall short in critical ways. In this article, we discuss what compositional explanations are, their role in scientific inquiry, and their importance for psychopathology research and practice. We then explain why current descriptive accounts of mental disorder fall short of providing such an explanation and demonstrate how effective compositional explanations could be constructed.

Shared Neural Phenotypes for Mood and Anxiety Disorders A Meta-Analysis of 226 Task-Related Functional Imaging Studies.

(Appeared originally in JAMA Psychiatry 2020;77(2):172-179).

Decision-making as transdiagnostic construct for mental health research

Transdiagnostic research and linking behavioral, neural, and symptom measures are important endeavors in clinical neuroscience and biological psychiatry. In this issue of Neuron, Moutoussis etal. (2021) describe a new cognitive construct-decision acuity-that is related to mental health symptoms and distinct resting-state networks.

The Ethical Conundrums of “Precision Psychiatry”

The Ethical Conundrums of “Precision Psychiatry”

Improving cognitive functioning in major depressive disorder with psychedelics: A dimensional approach

The high symptomatic and biological heterogeneity of major depressive disorder (MDD) makes it very difficult to find broadly efficacious treatments that work against all symptoms. Concentrating on single core symptoms that are biologically well understood might consist of a more viable approach. The Research Domain Criteria (RDoC) framework is a trans-diagnostic dimensional approach that focuses on symptoms and their underlying neurobiology. Evidence is accumulating that psychedelics may possess antidepressant activity, and this can potentially be explained through a multi-level (psychobiological, circuitry, (sub)cellular and molecular) analysis of the cognitive systems RDoC domain. Cognitive deficits, such as negative emotional processing and negativity bias, often lead to depressive rumination. Psychedelics can increase long-term cognitive flexibility, leading to normalization of negativity bias and reduction in rumination. We propose a theoretical model that explains how psychedelics can reduce the negativity bias in depressed patients. At the psychobiological level, we hypothesize that the negativity bias in MDD is due to impaired pattern separation and that psychedelics such as psilocybin help in depression because they enhance pattern separation and hence reduce negativity bias. Pattern separation is a mnemonic process that relies on adult hippocampal neurogenesis, where similar inputs are made more distinct, which is essential for optimal encoding of contextual information. Impairment in this process may underlie the negative cognitive bias in MDD by, for example, increased pattern separation of cues with a negative valence that can lead to excessive deliberation on aversive outcomes. On the (sub) cellular level, psychedelics stimulate hippocampal neurogenesis as well as synaptogenesis, spinogenesis and dendritogenesis in the prefrontal cortex. Together, these effects help restoring resilience to chronic stress and lead to modulation of the major connectivity hubs of the prefrontal cortex, hippocampus, and amygdala. Based on these observations, we propose a new translational framework to guide the development of a novel generation of therapeutics to treat the cognitive symptoms in MDD.

Neural correlates of RDoC-specific cognitive processes in a high-functional autistic patient: a statistically validated case report

The level of functioning of individuals with autism spectrum disorder (ASD) varies widely. To better understand the neurobiological mechanism associated with high-functioning ASD, we studied the rare case of a female patient with an exceptional professional career in the highly competitive academic field of Mathematics. According to the Research Domain Criteria (RDoC) approach, which proposes to describe the basic dimensions of functioning by integrating different levels of information, we conducted four fMRI experiments targeting the (1) social processes domain (Theory of mind (ToM) and face matching), (2) positive valence domain (reward processing), and (3) cognitive domain (N-back). Patient’s data were compared to data of 14 healthy controls (HC). Additionally, we assessed the subjective experience of our case during the experiments. The patient showed increased response times during face matching and achieved a higher total gain in the Reward task, whereas her performance in N-back and ToM was similar to HC. Her brain function differed mainly in the positive valence and cognitive domains. During reward processing, she showed reduced activity in a left-hemispheric frontal network and cortical midline structures but increased connectivity within this network. During the working memory task patients’ brain activity and connectivity in left-hemispheric temporo-frontal regions were elevated. In the ToM task, activity in posterior cingulate cortex and temporo-parietal junction was reduced. We suggest that the high level of functioning in our patient is rather related to the effects in brain connectivity than to local cortical information processing and that subjective report provides a fruitful framework for interpretation.

The forced swim test: Giving up on behavioral despair (Commentary on Molendijk & de Kloet, 2021).

The forced swim test: Giving up on behavioral despair (Commentary on Molendijk & de Kloet, 2021).

Morphometry of the Hippocampus Across the Adult Life-Span in Patients with Depressive Disorders: Association with Neuroticism.

Neuroticism is one of the main endophenotypes of major depressive disorder (MDD) and is closely related to the negative effect systems of Research Domain Criteria (RDoC) domains. The relationship between neuroticism and aging is dynamic and complex. Moreover, reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with MDD. However, it remains unclear to what extent hippocampal abnormalities are linked with age and neuroticism changes in people with depression through the adult life span. This study aimed to examine the interplay between aging and neuroticism on hippocampal morphometric across the adult life-span in a relative large sample of patients with depressive disorders (114 patients, 73 females, age range: 18-74 years) and healthy control (HC) subjects (112 healthy controls, 72 females, age range: 19-72 years). MDD patients showed reduced bilateral hippocampal volumes. The effect of aging on the left hippocampal showed linear and the right hippocampal volume non-linear trajectories throughout the adult life span in healthy groups and MDD groups respectively. The hippocampal atrophy was dynamically impacted by depression at the early stages of adult life. Furthermore, we observed that right hippocampal volume reduction was associated with higher neuroticism in depressive patients younger than 30.65 years old. Our results suggest that the age-related atrophy in the right hippocampal volume was more affected by individual differences in neuroticism among younger depressive patients. Hippocampal volume reduction as a vulnerability factor for early-onset and major geriatric depression may have a distinct endophenotype.

TDAH dans l’enfance et trouble psychotique à l’âge adulte : quel lien ?

ObjectivesAttention Deficit with/without Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with frequent comorbid psychiatric disorders. Several studies have underlined the increased risk of developing a psychotic disorder subsequent to a childhood ADHD. The aim of our review is not only to clarify this association and the related physiopathology but also to understand the consequences for therapeutic management. MethodsWe processed a narrative review of available literature based on a research of the PubMed database. Articles related to ADHD and psychotic disorder on a genetical, clinical or biological level were selected by one of the authors. ResultsADHD and psychotic disorders share neonatal, environmental, and genetic risk factors. On a neurobiological level, both disorders are concerned by a dysfunction of the dopaminergic system with an abnormal regulation of dopaminergic neurons’ phasic and tonic activity. Our review aims to explain the « dynamic » model of dopaminergic dysfunctions and propose some guidance for pharmacological treatment of ADHD, with or without psychotic disorder. This model offers a better understanding of why methylphenidate is not associated to an increased risk of psychotic disorder and could act as a protective factor. Association between ADHD and psychotic disorders could be explained by some comorbidities such as substance use disorders which are frequently associated with both conditions and could act as mediator in the genesis of psychotic disorders following ADHD during childhood. Our review also focuses on an epidemiological bias that could be found in some studies such as possible diagnostic errors, as some non-specific clinical signs could be found in both late diagnosed ADHD and in “at risk mental state” of psychosis. ConclusionADHD and psychotic disorders share common risk factors, neurobiological pathways and clinical symptoms. Perspectives for future studies are proposed considering a dimensional aspect of psychiatric disorders using, for example, Research Domain Criteria and exploring the link between the two conditions.

Neural correlates of alcohol use disorder severity among nontreatment-seeking heavy drinkers: An examination of the incentive salience and negative emotionality domains of the alcohol and addiction research domain criteria.

The Alcohol and Addiction Research Domain Criteria (AARDoC) propose that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively. Yet studies examining such cue-induced changes in functional connectivity (FC) are relatively sparse. Nontreatment-seeking heavy drinking adults (N=149, 56.0% male, 48.6% non-white, mean age 34.8years (SD=10.0)) underwent functional magnetic resonance imaging during presentation of alcohol, negative, and neutral pictures. We focused on FC changes involving the nucleus accumbens and amygdala in addition to activation and FC correlations with self-reported AUD severity. For alcohol cues versus neutral cues, we observed accumbens FC changes in the cerebellum and prefrontal cortex (PFC), and amygdala FC changes with occipital, parietal, and hippocampal regions. AUD severity correlated positively with activation in the cerebellum (p<0.05), accumbens FC in the cingulate gyri, somatosensory gyri, and cerebellum (p<0.05), and with amygdala FC in the PFC and inferior parietal lobule (p<0.05) for alcohol cues versus neutral cues. For negative cues versus neutral cues, we observed accumbens FC changes in the lateral temporal, occipital, and parietal regions, and amygdala FC changes in the fusiform and lingual gyri (p<0.05). The present findings provide empirical support for the AARDoC domains of incentive salience and negative emotionality and indicate that AUD severity is associated with salience and response control for reward cues. When covarying for differences in nonalcohol substance use and mood disorder diagnoses, AUD severity was also associated with emotional reactivity for negative cues.

Association Between RDoC Construct Negative Valence Domain Trajectories and Posttraumatic Stress Symptom Cluster Domain Trajectories in the Aftermath of Trauma: Results From the Aurora Study

Research domain criteria (RDoC) for the negative valence systems domain include acute threat (AT/“fear”), potential threat (PT/“anxiety”), and sustained threat (ST). We examined characteristics of, and associations between, posttraumatic recovery trajectories evaluated using RDoC negative valence domain concepts and DSM-based posttraumatic stress symptom clusters (PTSSC) (avoidance (Av), re-experiencing (Re), and hyperarousal (Ha).

Prosocial Learning and Decision-Making in Young Adults With Alcohol Use Disorder

Addiction is associated with deficits in social cognition but it is still unknown how to reliably measure these as social behavioural deficits. Consistent with Research Domain Criteria, we objectively quantified behaviour using neuroeconomic games of social learning and decision-making.

Error-related negativity: neurocognitive transdiagnostic marker of anxiety disorders

The article is devoted to the analysis of the prospects for research on neurocognitive mechanisms of anxiety disorders. In response to limitations and contradictions in the logic of the categorical method of classification of mental disorders, the popularity of the dimensional approach, in which the emphasis shifts to the assessment of the severity of symptoms. The National Institute of Mental Health has developed the promising approach based on the search for systemic neurobiological foundations of mental disorders. Based on the project RDoC (Research Domain Criteria) the search for trans-diagnostic mechanisms of mental disorders has been updated. The logic of RDoC echoes the position of Russian pathopsychology, in which the syndrome of mental activity disorders is considered in dynamics, the mechanisms of the functioning of the psyche are qualified as identical in norm and pathology. In the study of anxiety-related disorders, the obvious commonality of the spectrum of manifestations that acquire nosological clarification against the background of the escalation of the severity of symptoms and secondary compensatory processes has repeatedly been put forward in the center of research attention. The aim of the article is a theoretical and methodological analysis of the neurocognitive basis of the errors monitoring system, characteristic of normal and excessively expressed in anxiety disorders, including ERP component error related negativity (ERN). As a result, it is shown that this neurocogitive marker, experimentally modeled in conflict tasks (e.g., Eriksens flanker task), is expected to be a probable transdiagnostic basis for anxiety-related disorders (social anxiety disorder, obsessive-compulsive disorder). The increase in the amplitude of ERN in internalization, uniting anxiety-depressive symptoms, is explained by individual differences in the readiness to detect error and sensitivity to incorrect decisions. At the moment, the study of ERN retains the tempted of simplified interpretations, the arbitrary establishment of direct causal connections between the neural basis and mental phenomena.

Motor and sensory features successfully decode autism spectrum disorder and combine with the original RDoC framework to boost diagnostic classification

Sensory processing and motor coordination atypicalities are not commonly identified as primary characteristics of autism spectrum disorder (ASD), nor are they well captured in the NIMH’s original Research Domain Criteria (RDoC) framework. Here, motor and sensory features performed similarly to RDoC features in support vector classification of 30 ASD youth against 33 typically developing controls. Combining sensory with RDoC features boosted classification performance, achieving a Matthews Correlation Coefficient (MCC) of 0.949 and balanced accuracy (BAcc) of 0.971 (p = 0.00020, calculated against a permuted null distribution). Sensory features alone successfully classified ASD (MCC = 0.565, BAcc = 0.773, p = 0.0222) against a clinically relevant control group of 26 youth with Developmental Coordination Disorder (DCD) and were in fact required to decode against DCD above chance. These findings highlight the importance of sensory and motor features to the ASD phenotype and their relevance to the RDoC framework.