Effects of acute stress on reward processing: A comprehensive meta-analysis of rodent and human studies.

Stressors can initiate a cascade of central and peripheral changes that modulate mesocorticolimbic dopaminergic circuits and, ultimately, behavioral response to rewards. Driven by the absence of conclusive evidence on this topic and the Research Domain Criteria framework, random-effects meta-analyses were adopted to quantify the effects of acute stressors on reward responsiveness, valuation, and learning in rodent and human subjects. In rodents, acute stress reduced reward responsiveness (g = -1.43) and valuation (g = -0.32), while amplifying reward learning (g = 1.17). In humans, acute stress had marginal effects on valuation (g = 0.25), without affecting responsiveness and learning. Moderation analyses suggest that acute stress neither has unitary effects on reward processing in rodents nor in humans and that the duration of the stressor and specificity of reward experience (i.e., food vs drugs) may produce qualitatively and quantitatively different behavioral endpoints. Subgroup analyses failed to reduce heterogeneity, which, together with the presence of publication bias, pose caution on the conclusions that can be drawn and point to the need of guidelines for the conduction of future studies in the field.

Atypical local and global biological motion perception in children with attention deficit hyperactivity disorder.

Perceiving biological motion (BM) is crucial for human survival and social interaction. Many studies have reported impaired BM perception in autism spectrum disorder, which is characterised by deficits in social interaction. Children with attention deficit hyperactivity disorder (ADHD) often exhibit similar difficulties in social interaction. However, few studies have investigated BM perception in children with ADHD. Here, we compared differences in the ability to process local kinematic and global configurational cues, two fundamental abilities of BM perception, between typically developing and ADHD children. We further investigated the relationship between BM perception and social interaction skills measured using the Social Responsiveness Scale and examined the contributions of latent factors (e.g. sex, age, attention, and intelligence) to BM perception. The results revealed that children with ADHD exhibited atypical BM perception. Local and global BM processing showed distinct features. Local BM processing ability was related to social interaction skills, whereas global BM processing ability significantly improved with age. Critically, general BM perception (i.e. both local and global BM processing) may be affected by sustained attentional ability in children with ADHD. This relationship was primarily mediated by reasoning intelligence. These findings elucidate atypical BM perception in ADHD and the latent factors related to BM perception. Moreover, this study provides new evidence that BM perception is a hallmark of social cognition and advances our understanding of the potential roles of local and global processing in BM perception and social cognitive disorders.

Dimensional measures of psychopathology in children and adolescents using large language models.

BACKGROUND: To enable greater use of NIMH Research Domain Criteria (RDoC) in real-world settings, we applied large language models to estimate dimensional psychopathology from narrative clinical notes. METHODS: We conducted a cohort study using health records from individuals age 18 years or younger evaluated in the psychiatric emergency department of a large academic medical center between November 2008 and March 2015. Outcomes were hospital admission and length of emergency department stay. RDoC domains were estimated using a HIPAA-compliant large language model (gpt-4-1106-preview), and compared to a previously-validated token-based approach. RESULTS: The cohort included 3,059 individuals (median age 16 (25%-75% 13-18); 1580 (52%) female, 1479 (48%) male; 105 (3.4%) identified as Asian, 329 (11%) as Black, 288 (9.4%) Hispanic, 474 (15%) as another race, and 1863 (61%) as white), of whom 1695 (55%) were admitted. Correlation between LLM-extracted RDoC scores and the token-based scores ranged from small to medium by Kendall's Tau (0.14-0.22). In logistic regression models adjusted for sociodemographic and clinical features, admission likelihood was associated with greater scores on all domains, with the exception of sensorimotor, which was inversely associated (p<.001 for all adjusted associations). Tests for bias suggested modest but statistically significant differences in positive valence scores by race (p<.05 for Asian, Hispanic, and Black individuals). CONCLUSION: A large language model extracted estimates of 6 RDoC domains in an explainable manner, which were associated with clinical outcomes. This approach can contribute to a new generation of prediction models or biological investigations based on dimensional psychopathology.

"Broken fragments or a breathtaking mosaic": A mixed methods study of self-reported attributes and aspirations of siblings of individuals with and without neurodevelopmental conditions.

Siblings of individuals with neurodevelopmental conditions (NDCs) experience distinct challenges and have unique strengths compared to siblings of individuals without NDCs. The present study examined attributes and aspirations of siblings of individuals with and without neurodevelopmental conditions, and analyzed the association between qualitative responses and quantitative measures of growth mindset, positive and negative valence, and mental health diagnoses. A novel mixed methods thematic analysis was employed to explore the experiences of 166 siblings (75 NDC and 91 controls, aged 14-26, 66.27% female) completing an online survey as part of a larger study on sibling mental health. The overarching theme described The Process of Self-Actualization and Integration, reflecting the journey siblings undergo in seeking to understand themselves and others amidst psychological challenges. It encompassed three subthemes: Personal Growth and Identity Formation; Connection and Belonginess; and Societal Perspective and Global Consciousness. Qualitative responses were analyzed within a Research Domain Criteria (RDoC) framework, and associations between phenomenology and mental health diagnoses examined. NDC siblings had higher negative valence and lower positive valence embedded in their responses, and quantitatively lower self-reported growth mindset (i.e., beliefs about the capacity for personal growth), compared to control siblings, which correlated with self-reported mental health diagnoses. Findings suggest clinical practice may focus on optimizing self-identified strengths and offer opportunities for self-actualization of hopes and ambitions, while providing support for families to attenuate bioecological factors impacting mental health.

Gut microbiota composition links to variation in functional domains across psychiatric disorders.

OBJECTIVE: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity. METHODS: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status. RESULTS: Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all pFDR < 0.05). CONCLUSION: Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways.

Applying the Research Domain Criteria to Rodent Studies of Sex Differences in Chronic Stress Susceptibility.

Women have a two-fold increased rate of stress-associated psychiatric disorders such as depression and anxiety, but the mechanisms of this increased susceptibility remain incompletely understood. Female subjects were historically excluded from preclinical studies and clinical trials. Additionally, chronic stress paradigms used to study psychiatric pathology in animal models were developed for use in males. However, recent changes in NIH policy encourage inclusion of female subjects, and considerable work has been performed in recent years to understand biological sex differences that may underlie differences in susceptibility to chronic stress associated psychiatric conditions. We here review the utility as well as current challenges of using the framework of the NIH's research domain criteria as a transdiagnostic approach to study sex differences in rodent models of chronic stress including recent progress in the study of sex differences in the neurobehavioral domains of negative valence, positive valence, cognition, social processes, arousal, and social processes.

Multiracial Reading the Mind in the Eyes Test (MRMET): An inclusive version of an influential measure.

Can an inclusive test of face cognition meet or exceed the psychometric properties of a prominent less inclusive test? Here, we norm and validate an updated version of the influential Reading the Mind in the Eyes Test (RMET), a clinically significant neuropsychiatric paradigm that has long been used to assess theory of mind and social cognition. Unlike the RMET, our Multiracial Reading the Mind in the Eyes Test (MRMET) incorporates racially inclusive stimuli, nongendered answer choices, ground-truth referenced answers, and more accessible vocabulary. We show, via a series of large datasets, that the MRMET meets or exceeds RMET across major psychometric indices. Moreover, the reliable signal captured by the two tests is statistically indistinguishable, evidence for full interchangeability. We thus present the MRMET as a high-quality, inclusive, normed and validated alternative to the RMET, and as a case in point that inclusivity in psychometric tests of face cognition is an achievable aim. The MRMET test and our normative and validation data sets are openly available under a CC-BY-SA 4.0 license at osf.io/ahq6n.

Disorder-specific versus transdiagnostic cognitive mechanisms in anxiety and depression: Machine-learning-based prediction of symptom severity.

INTRODUCTION: Psychiatric evaluation of anxiety and depression is currently based on self-reported symptoms and their classification into discrete disorders. Yet the substantial overlap between these disorders as well as their within-disorder heterogeneity may contribute to the mediocre success rates of treatments. The proposed research examines a new framework for diagnosis that is based on alterations in underlying cognitive mechanisms. In line with the Research Domain Criteria (RDoC) approach, the current study directly compares disorder-specific and transdiagnostic cognitive patterns in predicting the severity of anxiety and depression symptoms. METHODS: The sample included 237 individuals exhibiting differing levels of anxiety and depression symptoms, as measured by the STAI-T and BDI-II. Random Forest regressors were used to analyze their performance on a battery of six computerized cognitive-behavioral tests targeting selective and spatial attention, expectancy, interpretation, memory, and cognitive control biases. RESULTS: Unique anxiety-specific biases were found, as well as shared anxious-depressed bias patterns. These cognitive biases exhibited relatively high fitting rates when predicting symptom severity (questionnaire scores common range 0-60, MAE = 6.03, RMSE = 7.53). Interpretation and expectancy biases exhibited the highest association with symptoms, above all other individual biases. LIMITATIONS: Although internal validation methods were applied, models may suffer from potential overfitting due to sample size limitations. CONCLUSION: In the context of the ongoing dispute regarding symptom-centered versus transdiagnostic approaches, the current study provides a unique comparison of these two views, yielding a novel intermediate approach. The results support the use of mechanism-based dimensional diagnosis for adding precision and objectivity to future psychiatric evaluations.

Arousal, Gray's theory of anxiety, and the etiology of psychopathy.

This paper focuses on Jeffrey Gray's theory of anxiety from the perspective of Fowles' (1980) application of his work to theories of arousal, psychophysiology, and the etiology of psychopathy. Although highly influential, the concept of general arousal failed to find support in terms of between-individuals assessment with multiple physiological measures. Gray's constructs of a behavioral inhibition system (BIS) that mediates anxiety, a behavioral approach or activation system (BAS) that energizes behavior to approach rewards, and a nonspecific arousal system that energizes behavior captured aspects of arousal. Fowles (1980) proposed that the BIS elicits electrodermal activity in response to threats, the BAS increases heart rate in response to reward incentive cues, and psychopathy is associated with a weak BIS. The paper reviews Gray's impact on future research on these topics, including early proposals relevant to the National Institute of Mental Health's Research Domain Criteria. Finally, the paper summarizes the evolution of theories of the etiology of psychopathy since 1980, noting ways in which aspects of Gray's theory are still seen in psychopathy research. Patrick's triarchic model has emerged as a major theory of psychopathy. Beauchaine's trait impulsivity theory of Attention Deficit Hyperactivity Disorder also is relevant.

Neuropsychological assessment of aggressive offenders: a Delphi consensus study.

Objective: This study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression. Methods: An international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability. Results: The panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed. Conclusions: This research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.

Clinical Psychology in the Era of Research Diagnostic Criteria (RDoC): Reconciling Individually-Focused Practice with a Broader Biopsychosocial Context.

There is growing consensus that diagnostic labels are insufficient to describe the individual child's psychiatric profile, much less inform the precise combination of interventions that will minimize the impact of risk and/or bolster protective factors over the course of a particular child's development. Moreover, investigations of neurobiological and genetic mechanisms associated with psychopathology have revealed considerable cross-diagnostic overlap, undermining the validity of models that propose a 1:1 relationship between risk and psychiatric disorder. Accordingly, recent publications have advocated for neurodevelopmental models that utilize trait-based measurement, as well as increased emphasis on integration of biological and experiential mechanisms. Despite an expanding body of literature supporting this conceptual shift, the practical implications remain unclear. In this special issue, we compile a collection of novel empirical research papers and reviews that build on the trans-diagnostic principles of the RDoC framework.

[Diagnosis and admission center : Establishment and evaluation of an integrated translational infrastructure for clinical psychiatric research]. / Diagnose- und Aufnahmezentrum : Etablierung und Evaluation einer integrierten translationalen Infrastruktur für die klinisch-psychiatrische Forschung.

The routine in-depth characterization of patients with methods of clinical and scale-based examination, neuropsychology, based on biomaterials, and sensor-based information opens up transformative possibilities on the way to personalized diagnostics, treatment and prevention in psychiatry, psychotherapy, and psychosomatics. Effective integration of the additional temporal and logistical effort into everyday care as well as the acceptance by patients are critical to the success of such an approach but there is little evidence on this to date. We report here on the establishment of the Diagnosis and Admission Center (DAZ) at the Central Institute of Mental Health (ZI) in Mannheim. The DAZ is an outpatient unit upstream of other care structures for clinical and scientific phenotyping across diagnoses as a starting point for data-driven, individualized pathways to further treatment, diagnostics or research. We describe the functions, goals, and implementation of the newly created clinical scientific translational structure, provide an overview of the patient populations it has reached, and provide data on its acceptance. In this context, the close integration with downstream clinical processes enables a better coordinated and demand-oriented allocation. In addition, DAZ enables a faster start of disorder-specific diagnostics and treatment. Since its launch in April 2021 up to the end of 2022, 1021 patients underwent psychiatric evaluation at DAZ during a pilot phase. The patient sample corresponded to a representative sample from standard care and the newly established processes were regarded as helpful by patients. In summary, the DAZ uniquely combines the interests and needs of patient with the collection of scientifically relevant data.

Explaining Brain-Behavior Relations: Inhibitory Control as an Intermediate Phenotype Between the N2 ERP and the Externalizing Spectrum in Childhood.

Identifying neural and cognitive mechanisms in externalizing problems in childhood is important for earlier and more targeted intervention. Meta-analytic findings have shown that smaller N2 event-related potential (ERP) amplitudes, thought to reflect inhibitory control, are associated with externalizing problems in children. However, it is unclear how (i.e., through which cognitive processes) N2 amplitudes relate to externalizing problems. We examined whether inhibitory control may be a cognitive process that links N2 amplitudes and externalizing problems in early childhood. Children (N = 147, 74 girls) were assessed at four time points, spanning 3-7 years of age. Children's externalizing behavior was assessed via questionnaires completed by mothers, fathers, and teachers/secondary caregivers. Children's inhibitory control was assessed using eleven performance-based tasks and two questionnaires. Developmental scaling linked differing measures of inhibitory control and externalizing behavior across ages onto the same scale. Children's N2 amplitudes were extracted from electroencephalography data collected during a go/no-go task. Smaller N2 amplitudes were associated with externalizing problems and poorer inhibitory control. A concurrent analysis of indirect effects revealed that poorer inhibitory control partially explained the association between smaller N2 amplitudes and externalizing problems, even when controlling for the child's age, sex, and socioeconomic status. This is among the first studies to link N2 amplitudes, inhibitory control, and externalizing problems during early childhood. Findings suggest that smaller N2 amplitudes may be an early neural indicator of inhibitory control deficits and externalizing psychopathology. Moreover, inhibitory control may be an important target for early intervention in the development of externalizing psychopathology.

Threat Responses in Schizophrenia: A Negative Valence Systems Framework.

PURPOSE OF REVIEW: Emotions are prominent in theories and accounts of schizophrenia but are largely understudied compared to cognition. Utilizing the Research Domain Criteria (RDoC) Negative Valence Systems framework, we review the current knowledge of emotions in schizophrenia. Given the pivotal role of threat responses in theories of schizophrenia and the substantial evidence of altered threat responses, we focus on three components of Negative Valence Systems tied to threat responses: responses to acute threat, responses to potential threat, and sustained threat. RECENT FINDINGS: Individuals with schizophrenia show altered responses to neutral stimuli during acute threat, bed nucleus of the stria terminalis connectivity in response to potential threat, and threat responses associated with sustained threat. Our review concludes that Negative Valence Systems are altered in schizophrenia; however, the level and evidence of alterations vary across the types of threat responses. We suggest avenues for future research to further understand and intervene on threat responses in schizophrenia.

Cool and hot executive function problems in young children: linking self-regulation processes to emerging clinical symptoms.

Self-regulation (SR) difficulties are implicated in a wide range of disorders which develop in childhood, including attention deficit hyperactivity disorder (ADHD), oppositional defiance disorder (ODD), anxiety and depression. However, the integration of the existing research evidence is challenging because of varying terminology and the wide range of tasks used, as well as the heterogeneity and comorbidity within and across diagnostic categories. The current study used the Research Domain Criteria (RDoC) framework to guide the examination of different SR processes in young children showing a wide range of symptomatology. Children (aged 4-8) referred by teachers for moderate-to-high conduct, hyperactivity and/or emotional problems at school (assessed using the Strengths and Difficulties Questionnaire (SDQ) subscales; n = 212), and children in SDQ typical ranges (n = 30) completed computerised cognitive control and decision-making tasks. Parents completed questionnaires to assess ADHD, ODD, anxiety and depression symptoms (n = 191). Compared to children with no teacher-reported difficulties, those with moderate-to-high problems showed poorer visuomotor control and decision-making. A factor analysis revealed that task variables adhered to RDoC dimensions and predicted variance in specific disorders: difficulties in cognitive control predicted ADHD symptoms, low reward-seeking was associated with depression and high reward-seeking was associated with ODD. This study highlights how the assessment of cognitive processes positioned within the RDoC framework can inform our understanding of disorder-specific and transdiagnostic difficulties in SR which are associated with diverse clinical symptoms in children.

Theta oscillatory dynamics serving cognitive control index psychosocial distress in youth.

Background: Psychosocial distress among youth is a major public health issue characterized by disruptions in cognitive control processing. Using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we quantified multidimensional neural oscillatory markers of psychosocial distress serving cognitive control in youth. Methods: The sample consisted of 39 peri-adolescent participants who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and the Eriksen flanker task during magnetoencephalography (MEG). A psychosocial distress index was computed with exploratory factor analysis using assessments from the NIHTB-EB. MEG data were analyzed in the time-frequency domain and peak voxels from oscillatory maps depicting the neural cognitive interference effect were extracted for voxel time series analyses to identify spontaneous and oscillatory aberrations in dynamics serving cognitive control as a function of psychosocial distress. Further, we quantified the relationship between psychosocial distress and dynamic functional connectivity between regions supporting cognitive control. Results: The continuous psychosocial distress index was strongly associated with validated measures of pediatric psychopathology. Theta-band neural cognitive interference was identified in the left dorsolateral prefrontal cortex (dlPFC) and middle cingulate cortex (MCC). Time series analyses of these regions indicated that greater psychosocial distress was associated with elevated spontaneous activity in both the dlPFC and MCC and blunted theta oscillations in the MCC. Finally, we found that stronger phase coherence between the dlPFC and MCC was associated with greater psychosocial distress. Conclusions: Greater psychosocial distress was marked by alterations in spontaneous and oscillatory theta activity serving cognitive control, along with hyperconnectivity between the dlPFC and MCC.

Evidentiary Significance of Routine EEG in Refractory Cases: A Paradigm Shift in Psychiatry.

Over the past decade, the Diagnostic and Statistical Manual's method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association's posit that a paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGs were analyzed by the same neurophysiologist (board certified in electroencephalography) on 1,233 patients. This study identified 4 EEG biomarkers accounting for medication failure in refractory patients: focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges. Each EEG biomarker suggests underlying brain dysregulation, which may explain why prior medication attempts have failed. The EEG biomarkers cannot be identified based on current psychiatric assessment methods, and depending upon the localization, intensity, and duration, can all present as complex behavioral or psychiatric issues. The study highlights that the EEG biomarker identification approach can be a positive step toward personalized medicine in psychiatry, furthering the clinical thinking of "testing the organ we are trying to treat."

Integrating Biobehavioral and Environmental Components of Developmental Psychopathology via Interpersonal Dynamics: An RDoC-Advancing Model.

Although the Research Diagnostic Criteria (RDoC) framework proposes biological and environmental mechanisms intersect in the etiology of psychopathology, there is no guidance on how to define or measure experiences in the environment within the RDoC matrix. Interpersonal dynamics during caregiver-child interactions involve temporal coordination of interacting partners' biobehavioral functioning; repeated experiences of signaling to caregivers and responding to caregivers' signals shape children's subsequent socioemotional and brain development. We begin with a review of the extant literature on caregiver-child dynamics, which reveals that RDoC's units of analysis (brain circuits, physiology, behavior, and self-report) are inextricably linked with moment-to-moment changes in the caregiving environment. We then offer a proof-of-concept for integrating biobehavioral RDoC units and environmental components via caregiver-child dynamics. Our approach uses dynamic structural equation models to estimate within-dyad dynamics involving arousal, social, cognitive, and negative or positive affective processes based on second-by-second changes in parasympathetic activity (RSA) during a conflict discussion and a positive event-planning task. Our results illustrate variation in parent-child RSA synchrony, suggesting differences depending on the driver (i.e., child- or parent-led) and on the unique and intersecting domains involved (e.g., positive or negative affect valence systems). We conclude with recommendations for conducting robust, methodologically rigorous studies of interpersonal dynamics that advance the RDoC framework and provide a summary of the clinical implications of this research. Examining caregiver-child dynamics during and across multiple dyadic interaction paradigms that differentially elicit key domains of functioning can deepen understanding of how caregiver- and child-led interpersonal dynamics contribute to child psychopathology risk.

Translational In Vivo Assays in Behavioral Biology.

The failure of preclinical research to advance successful candidate medications in psychiatry has created a paradigmatic crisis in psychiatry. The Research Domain Criteria (RDoC) initiative was designed to remedy this situation with a neuroscience-based approach that employs multimodal and cross-species in vivo methodology to increase the probability of translational findings and, consequently, drug discovery. The present review underscores the feasibility of this methodological approach by briefly reviewing, first, the use of multidimensional and cross-species methodologies in traditional behavioral pharmacology and, subsequently, the utility of this approach in contemporary neuroimaging and electrophysiology research-with a focus on the value of functionally homologous studies in nonhuman and human subjects. The final section provides a brief review of the RDoC, with a focus on the potential strengths and weaknesses of its domain-based underpinnings. Optimistically, this mechanistic and multidimensional approach in neuropsychiatric research will lead to novel therapeutics for the management of neuropsychiatric disorders.

If Opportunity Knocks: Understanding Contextual Factors' Influence on Cognitive Systems.

Central to the Research Domain Criteria (RDoC) framework is the idea that RDoC constructs, which vary dimensionally by individual, are heavily influenced by contextual factors. Perhaps chief among these contextual factors is structural opportunity - the quality of resources available to a child as they grow. The aim of this study is to understand the impact of access to opportunity during childhood on three central RDoC cognitive systems constructs: language, visual perception, and attention. These constructs were measured using clinical data from psychological evaluations of youth ages 4-18 years (N = 16,523; Mage = 10.57, 62.3% male, 55.3% White). Structural opportunity was measured using the geocoded Child Opportunity Index 2.0 (COI), a composite score reflecting 29 weighted indicators of access to the types of neighborhood conditions that help children thrive. Findings indicate that, controlling for demographic and socioeconomic factors, greater access to opportunity is associated with significantly stronger cognitive skills across all three constructs. However, opportunity uniquely explains the largest proportion of the variance in language skills (8.4%), compared to 5.8% of the variance in visual processing skills and less than 2% of the variance in attention. Further, a moderating effect of age was found on the relation between COI and language skills, suggesting that the longer children remain exposed to lower levels of opportunity, the lower their language skills tend to be. Understanding how opportunity impacts cognitive development allows clinicians to offer better tailored recommendations to support children with cognitive systems deficits, and will support policy recommendations around access to opportunity.