Ellen Leibenluft’s research while affiliated with National Institute of Mental Health and Neuro Sciences and other places

Objective Quantifying relevant behavioral mechanisms has relied on rigorous, time-consuming tools restricted to laboratory settings and inaccessible to the clinical community. Advances in technology provide an opportunity to develop more accessible platforms. Here, we developed CALM-IT, a novel mobile-application to experimentally assess inhibitory control in vivo Method In a transdiagnostic sample of 200 youth aged 8–20, we (i) apply knowledge from canonical inhibitory control tasks in the methodological design of the mobile application, (ii) establish feasibility and engagement with CALM-IT, (iii) assess test-retest reliability of CALM-IT, (iv) investigate the convergent validity of CALM-IT with behavioral and neural responses to laboratory-based tasks, and (v) probe clinical relevance via associations with clinical symptoms. Results First, we provide evidence that our novel inhibitory control mobile application, CALM-IT, was accessible, feasible, and engaging. Second, we found performance was reliable over time. Third, we found CALM-IT performance was associated with established measures of inhibitory control and activation in the bilateral inferior frontal gyrus. Associations with brain but not behavior survived after controlling for age. Finally, we found evidence linking impaired CALM-IT performance to increased levels of co-occurring anxiety, irritability, and attention deficit hyperactivity disorder (ADHD) symptoms. Conclusion Validation of this neuroscience-informed mobile application represents a critical first step in bridging precise, mechanism-driven research and community-based assessment of childhood psychopathology. The present work lays the groundwork for future research that could provide researchers and clinicians with a multifaceted tool to measure clinically-relevant behaviors in an engaging and accessible manner.

BACKGROUND As Virtual Reality (VR) technology becomes increasingly prevalent, its potential for collecting objective behavioral data in psychiatric settings has been widely recognized. However, the lack of standardized methodologies limits reproducibility and data integration across studies, particularly in assessing attention deficit hyperactivity disorder (ADHD) and associated behaviors such as irritability and aggression. OBJECTIVE This study examines the utility of VR-based movement data to operationalize core ADHD symptoms (hyperactivity and inattention) and comorbid disruptive behaviors (irritability and aggression), aiming to identify reproducible and clinically actionable metrics. METHODS Forty-five children (mean age = 9.06 years, SD = 2.11; 14 female) participated, including 28 diagnosed with ADHD and 17 controls. Seven VR-derived movement variables were analyzed: average speed, acceleration, total distance, area occupied, distance between hands and head, frequency of movement, and time spent still. Correlation and regression analyses identified which variables best predicted ADHD symptoms and comorbid behaviors. RESULTS Total distance emerged as the strongest predictor of hyperactivity (β = 0.52, p < 0.01), while average speed was inversely associated with inattention (β = -0.45, p < 0.05) and positively correlated with aggression (β = 0.38, p < 0.05). More frequent but less intense movements predicted lower irritability (β = -0.41, p < 0.05) and aggression (β = -0.36, p < 0.05). These findings highlight consistent patterns, underscoring the potential of VR-derived movement variables as standardized metrics. CONCLUSIONS This study emphasizes the importance of standardized VR methodologies to enhance reproducibility and data integration in psychiatric research. By identifying specific movement variables that reliably predict ADHD and comorbid behaviors, the findings establish a foundation for developing scalable VR tools for clinical assessment and intervention.

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8–18 years old) with varying symptom types and levels. Participants were recruited from the Washington, D.C., metro region. Results of structural equation modeling integrating a bifactor model of psychopathology revealed that inhibitory control predicted a shared or general psychopathology dimension, but not ADHD-specific, anxiety-specific, or irritability-specific dimensions. Inhibitory control also showed a significant, selective association with global efficiency in a frontoparietal control network delineated during resting-state functional magnetic resonance imaging. These results support performance-based inhibitory control linked to resting-state brain function as an important predictor of comorbidity in youth psychopathology.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Objective: The authors investigated the neural impact of intranasal oxytocin on emotion processing areas in youths with severe irritability in the context of disruptive mood and behavior disorders. Methods: Fifty-two participants with severe irritability, as measured by a score ≥4 on the Affective Reactivity Index (ARI), with diagnoses of disruptive behavior disorders (DBDs) and/or disruptive mood dysregulation disorder (DMDD) were randomly assigned to treatment with intranasal oxytocin or placebo daily for 3 weeks. Assessments were conducted at baseline and at the end of the trial; the primary outcomes were measures of irritability on the ARI and ratings on the Clinical Global Impressions severity scale (CGI-S) focusing on DBD and DMDD symptoms, and secondary outcomes included the CGI improvement scale (CGI-I) and ratings of proactive and reactive aggressive behavior on the Reactive-Proactive Aggression Questionnaire. Forty-three participants (22 in the oxytocin group and 21 in the placebo group) completed pre- and posttreatment functional MRI (fMRI) scans with the affective Stroop task. Results: Youths who received oxytocin showed significant improvement in CGI-S and CGI-I ratings compared with those who received placebo. In the fMRI data, blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex were significantly reduced after oxytocin compared with placebo. These BOLD response changes were correlated with improvement in clinical severity. Conclusions: This study provides initial and preliminary evidence that intranasal oxytocin may induce neural-level changes in emotion processing in youths with irritability in the context of DBDs and DMDD. This may lead to symptom and severity changes in irritability.