Sleepless nights, sour moods: daily sleep-irritability links in a pediatric clinical sample.

BACKGROUND: Sleep, or a lack thereof, is strongly related to mood dysregulation. Although considerable research uses symptom scales to examine this relation, few studies use longitudinal, real-time methods focused on pediatric irritability. This study leveraged an ecological momentary assessment (EMA) protocol, assessing bidirectional associations between momentary irritability symptoms and daily sleep duration in a transdiagnostic pediatric sample enriched for irritability. METHODS: A total of N = 125 youth (Mage = 12.58 years, SD = 2.56 years; 74% male; 68.8% White) completed digital, in vivo surveys three times a day for 7 days. For a subset of youth, their parents also completed the EMA protocol. Trait irritability was measured using youth-, parent-, and clinician-report to test its potential moderating effect on the association between sleep duration and momentary irritability. RESULTS: Results from multilevel modeling dynamically linked sleep to irritability. Specifically, according to youth- and parent-report, decreased sleep duration was associated with increased morning irritability (bs ≤ -.09, ps < .049). A bidirectional association between parent-reported nightly sleep duration and anger was found-increased evening anger related to decreased nightly sleep duration, and decreased sleep duration related to increased morning anger (bs ≤ -.17, ps < .019). Trait irritability moderated this association, which was stronger for more irritable youth (b = -.03, p < .027). CONCLUSIONS: This study adds to the literature and suggests sleep-irritability dynamics as a potential treatment target.

Selecting an Ecological Momentary Assessment Platform: Tutorial for Researchers.

BACKGROUND: Although ecological momentary assessment (EMA) has been applied in psychological research for decades, delivery methods have evolved with the proliferation of digital technology. Technological advances have engendered opportunities for enhanced accessibility, convenience, measurement precision, and integration with wearable sensors. Notwithstanding, researchers must navigate novel complexities in EMA research design and implementation. OBJECTIVE: In this paper, we aimed to provide guidance on platform selection for clinical scientists launching EMA studies. METHODS: Our team includes diverse specialties in child and adolescent behavioral and mental health with varying expertise on EMA platforms (eg, users and developers). We (2 research sites) evaluated EMA platforms with the goal of identifying the platform or platforms with the best fit for our research. We created a list of extant EMA platforms; conducted a web-based review; considered institutional security, privacy, and data management requirements; met with developers; and evaluated each of the candidate EMA platforms for 1 week. RESULTS: We selected 2 different EMA platforms, rather than a single platform, for use at our 2 research sites. Our results underscore the importance of platform selection driven by individualized and prioritized laboratory needs; there is no single, ideal platform for EMA researchers. In addition, our project generated 11 considerations for researchers in selecting an EMA platform: (1) location; (2) developer involvement; (3) sample characteristics; (4) onboarding; (5) survey design features; (6) sampling scheme and scheduling; (7) viewing results; (8) dashboards; (9) security, privacy, and data management; (10) pricing and cost structure; and (11) future directions. Furthermore, our project yielded a suggested timeline for the EMA platform selection process. CONCLUSIONS: This study will guide scientists initiating studies using EMA, an in vivo, real-time research tool with tremendous promise for facilitating advances in psychological assessment and intervention.

Network analysis of ecological momentary assessment identifies frustration as a central node in irritability.

BACKGROUND: Irritability presents transdiagnostically, commonly occurring with anxiety and other mood symptoms. However, little is known about the temporal and dynamic interplay among irritability-related clinical phenomena. Using a novel network analytic approach with smartphone-based ecological momentary assessment (EMA), we examined how irritability and other anxiety and mood symptoms were connected. METHODS: Sample included 152 youth ages 8-18 years (M ± SD = 12.28 ± 2.53; 69.74% male; 65.79% White) across several diagnostic groups enriched for irritability including disruptive mood dysregulation disorder (n = 34), oppositional defiant disorder (n = 9), attention-deficit/hyperactivity disorder (n = 47), anxiety disorder (n = 29), and healthy comparisons (n = 33). Participants completed EMA on irritability-related constructs and other mood and anxiety symptoms three times a day for 7 days. EMA probed symptoms on two timescales: "since the last prompt" (between-prompt) versus "at the time of the prompt" (momentary). Irritability was also assessed using parent-, child- and clinician-reports (Affective Reactivity Index; ARI), following EMA. Multilevel vector autoregressive (mlVAR) models estimated a temporal, a contemporaneous within-subject and a between-subject network of symptoms, separately for between-prompt and momentary symptoms. RESULTS: For between-prompt symptoms, frustration emerged as the most central node in both within- and between-subject networks and predicted more mood changes at the next timepoint in the temporal network. For momentary symptoms, sadness and anger emerged as the most central node in the within- and between-subject network, respectively. While anger was positively related to sadness within individuals and measurement occasions, anger was more broadly positively related to sadness, mood lability, and worry between/across individuals. Finally, mean levels, not variability, of EMA-indexed irritability were strongly related to ARI scores. CONCLUSIONS: This study advances current understanding of symptom-level and temporal dynamics of irritability. Results suggest frustration as a potential clinically relevant treatment target. Future experimental work and clinical trials that systematically manipulate irritability-related features (e.g. frustration, unfairness) will elucidate the causal relations among clinical variables.

Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol.

BACKGROUND: Irritability, an increased proneness to anger, is a primary reason youth present for psychiatric care. While initial evidence supports the efficacy of exposure-based cognitive behavioral therapy (CBT) for youth with clinically impairing irritability, treatment mechanisms remain unclear. Here, we propose to measure peripheral psychophysiological indicators of arousal-heart rate (HR)/electrodermal activity (EDA)-and regulation-heart rate variability (HRV)-during exposures to anger-inducing stimuli as potential predictors of treatment efficacy. The objective of this study is to evaluate whether in-situ biosensing data provides peripheral physiological indicators of in-session response to exposures. METHODS: Blood volume pulse (BVP; from which HR and HRV canl be derived) and EDA will be collected ambulatorily using the Empatica EmbracePlus from 40 youth (all genders; ages 8-17) undergoing six in-person exposure treatment sessions, as part of a multiple-baseline trial of exposure-based CBT for clinically impairing irritability. Clinical ratings of irritability will be conducted at baseline, weekly throughout treatment, and at 3-month and 6-month follow-ups via the Clinical Global Impressions Scale (CGI) and the Affective Reactivity Index (ARI; clinician-, parent-, and child-report). Multilevel modeling will be used to assess within- and between-person changes in physiological arousal and regulation throughout exposure-based CBT and to determine whether individual differences are predictive of treatment response. DISCUSSION: This study protocol leverages a wearable biosensor (Empatica) to continuously record HR/HRV (derived from BVP) and EDA during in-person exposure sessions for youth with clinically impairing irritability. Here, the goal is to identify changes in physiological arousal (EDA, HR) and regulation (HRV) over the course of treatment in tandem with changes in clinical symptoms. TRIAL REGISTRATION: The participants in this study come from an overarching clinical trial (trial registration numbers: NCT02531893 first registered on 8/25/2015; last updated on 8/25/2023). The research project and all related materials were submitted and approved by the appropriate Institutional Review Board of the National Institute of Mental Health (NIMH).

An Exposure-Based Cognitive-Behavioral Therapy for Youth with Severe Irritability: Feasibility and Preliminary Efficacy.

OBJECTIVE: Clinically impairing irritability and temper outbursts are among the most common psychiatric problems in youth and present transdiagnostically; however, few mechanistically informed treatments have been developed. Here, we test the acceptability, feasibility, and preliminary efficacy of a novel exposure-based treatment with integrated parent management skills for youth with severe irritability using a randomized between-subjects multiple baseline design. METHOD: N = 41 patients (Age, Mean (SD) = 11.23 years (1.85), 62.5% male, 77.5% white) characterized by severe and impairing temper outbursts and irritability were randomized to different baseline observation durations (2, 4, or 6 weeks) prior to active treatment; 40 participants completed the 12 session treatment of exposure-based cognitive-behavioral therapy for irritability with integrated parent management skills. Masked clinician ratings were acquired throughout baseline and treatment phases, as well as 3- and 6-months post-treatment. To examine acceptability and feasibility, drop-out rates and adverse events were examined. Primary clinical outcome measures included clinician-administered measures of irritability severity and improvement. Secondary clinical outcome measures included multi-informant measures of irritability, depression, anxiety, and attention-deficit/hyperactivity disorder symptoms. RESULTS: No patients dropped out once treatment began, and no adverse events were reported. Irritability symptoms improved during the active phase of treatment across all measurements (all ßs > -0.04, ps < .011, Cohen's d range: -0.33 to -0.98). Treatment gains were maintained at follow-up (all ßs(39) < -0.001, ps > .400). Sixty-five percent of patients were considered significantly improved or recovered post-treatment based on the primary clinician-rated outcome measure. CONCLUSIONS: Results support acceptability, feasibility, and preliminary efficacy of this novel treatment for youth with severe irritability. Limitations and future directions are also discussed.

Real-time assessment of positive and negative affective fluctuations and mood lability in a transdiagnostic sample of youth.

BACKGROUND: Emotional lability, defined as rapid and/or intense affect fluctuations, is associated with pediatric psychopathology. Although numerous studies have examined labile mood in clinical groups, few studies have used real-time assessments in a well-characterized transdiagnostic sample, and no prior study has included participants with disruptive mood dysregulation disorder (DMDD). The present study leverages ecological momentary assessment (EMA) to assess emotional lability in a transdiagnostic pediatric sample. METHODS: One hundred thirty participants ages 8-18 with primary diagnoses of DMDD, attention-deficit/hyperactivity disorder (ADHD), an anxiety disorder (ANX), or healthy volunteers completed a previously validated 1-week EMA protocol. Clinicians determined diagnoses based on semi-structured interviews and assessed levels of functional impairment. Participants reported momentary affective states and mood change. Composite scores of fluctuations in positive and negative affect were generated. Affect fluctuations were compared between diagnostic groups and tested for their association with functional impairment. RESULTS: Diagnostic groups differed in levels of negative and positive emotional lability. DMDD patients demonstrated the highest level of labile mood compared with other groups. Emotional lability was associated with global impairment in the whole sample. CONCLUSIONS: Both positive and negative emotional lability is salient in pediatric psychopathology and is associated with functional impairment, particularly in DMDD youth.

Attention-control training as an early intervention for veterans leaving the military: A pilot randomized controlled trial.

Transitioning out of the military can be a time of change and challenge. Research indicates that altered threat monitoring in military populations may contribute to the development of psychopathology in veterans, and interventions that adjust threat monitoring in personnel leaving the military may be beneficial. Australian Defence Force personnel (N = 59) transitioning from the military were randomized to receive four weekly sessions of either attention-control training or a placebo attention training. The primary outcome was symptoms of posttraumatic stress disorder (PTSD), as measured using the PTSD Checklist for DSM-5 (PCL-5) at posttreatment. Following training, participants who received attention-control training reported significantly lower levels of PTSD symptoms, Hedges' g = 0.86, 95% CI [0.37, 1.36], p = .004, and significantly improved work and social functioning, Hedges' g = 0.93, 95% CI [0.46, 1.39], p = .001, relative to those in the placebo condition. Moreover, no participants who received attention-control training worsened with regard to PTSD symptoms, whereas 23.8% of those who received the placebo attention training experienced an increase in PTSD symptoms. The preliminary findings from this pilot study add to a small body of evidence supporting attention-control training as a viable indicated early intervention approach for PTSD that is worthy of further research.

Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors.

The COVID-19 pandemic is a chronically stressful event, particularly for youth. Here, we examine (i) changes in mood and anxiety symtpoms, (ii) pandemic-related stress as a mediator of change in symptoms, and (ii) threat processing biases as a predictor of increased anxiety during the pandemic. A clinically well-characterized sample of 81 youth ages 8-18 years (M = 13.8 years, SD = 2.65; 40.7% female) including youth with affective and/or behavioral psychiatric diagnoses and youth without psychopathology completed pre- and during pandemic assessments of anxiety and depression and COVID-related stress. Forty-six youth also completed a threat processing fMRI task pre-pandemic. Anxiety and depression significantly increased during the pandemic (all ps < 0.05). Significant symptom change was partially mediated by pandemic stress and worries. Increased prefrontal activity in response to neutral faces pre-pandemic was associated with more intense parent-reported anxiety during the pandemic (all Fs(1.95,81.86) > 14.44, ps < 0.001). The present work extends existing knowledge on the mediating role of psychological stress on symptoms of anxiety and depression in youth.

Bias-contingent attention bias modification and attention control training in treatment of PTSD: a randomized control trial.

BACKGROUND: Randomized control trials (RCTs) comparing attention control training (ACT) and attention bias modification (ABM) in posttraumatic stress disorder (PTSD) have shown mixed results. The current RCT extends the extant literature by comparing the efficacy of ACT and a novel bias-contingent-ABM (BC-ABM), in which direction of training is contingent upon the direction of pre-treatment attention bias (AB), in a sample of civilian patients with PTSD. METHODS: Fifty treatment-seeking civilian patients with PTSD were randomly assigned to either ACT or BC-ABM. Clinician and self-report measures of PTSD and depression, as well as AB and attention bias variability (ABV), were acquired pre- and post-treatment. RESULTS: ACT yielded greater reductions in PTSD and depressive symptoms on both clinician-rated and self-reported measures compared with BC-ABM. The BC-ABM condition successfully shifted ABs in the intended training direction. In the ACT group, there was no significant change in ABV or AB from pre- to post-treatment. CONCLUSIONS: The current RCT extends previous results in being the first to apply ABM that is contingent upon AB at pre-treatment. This personalized BC-ABM approach is associated with significant reductions in symptoms. However, ACT produces even greater reductions, thereby emerging as a promising treatment for PTSD.

Validity of Attention Bias Variability Indices for Posttraumatic Stress Disorder Research: Evidence From Patient Data.

Although initial findings indicated that threat-related attention bias variability (ABV), an index designed to capture dynamic shifts in threat-related attention over time, was positively correlated with the severity of posttraumatic stress disorder (PTSD) symptoms, a recent study relying on simulated data has raised questions regarding the validity and empirical utility of ABV. Specifically, the simulations suggested that core features of reaction time data distinct from threat-related attention bias, such as the reaction time standard deviation and mean, could explicate the reported elevated ABV among samples with PTSD. In the present study, we evaluated these suggestions in 95 PTSD-diagnosed participants. The results showed that ABV significantly and uniquely predicted PTSD symptom severity beyond the predictive value of core reaction time features, ΔR2 = .05-.23. Some of the predictions stemming from the simulated results were replicated, whereas others were not. Contrary to the conclusion drawn from the simulated data, the results from the current study suggest that ABV is a valid and replicable correlate of PTSD symptom severity.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) La validez de los índices de variabilidad del sesgo de atención para la investigación del TEPT: Evidencia sobre los datos de los pacientes VALIDEZ DE LA VARIABILIDAD DEL SESGO ATENCIONAL EN EL TEPT Aunque los hallazgos iniciales indicaron que la variabilidad del sesgo de atención (ABV en su sigla en inglés) relacionada con la amenaza, un índice diseñado para capturar cambios dinámicos en la atención relacionada con la amenaza a lo largo del tiempo, que se correlacionó positivamente con la gravedad de los síntomas del trastorno de estrés postraumático (TEPT), un estudio reciente basado en datos simulados ha planteado preguntas sobre la validez y la utilidad empírica del ABV. Específicamente, las simulaciones sugirieron que las características centrales de los datos del tiempo de reacción distintas del sesgo de atención relacionado con la amenaza, como la desviación estándar y la media del tiempo de reacción, podrían explicar el aumento del ABV reportado entre las muestras con el TEPT. En el presente estudio, evaluamos estas sugerencias en 95 participantes con diagnóstico del TEPT. Los resultados mostraron que ABV predijo de manera significativa y única la gravedad de los síntomas del TEPT más allá del valor predictivo de las características centrales del tiempo de reacción, ΔR2 = .05 - .23. Algunas de las predicciones derivadas de los resultados simulados se replicaron, mientras que otras no. Contrariamente a la conclusión extraída de los datos simulados, los resultados del estudio actual sugieren que la ABV es un correlato válido y replicable de la gravedad de los síntomas del TEPT.

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

OBJECTIVE: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT. METHODS: Unmedicated youths diagnosed with an anxiety disorder underwent 12 weeks of CBT as part of two randomized clinical trials testing the efficacy of adjunctive computerized cognitive training. Across both trials, participants completed a threat-processing task during functional MRI before and after treatment. Age-matched healthy comparison youths completed two scans over the same time span. The mean age of the samples was 13.20 years (SD=2.68); 41% were male (youths with anxiety disorders, N=69; healthy comparison youths, N=62). An additional sample including youths at temperamental risk for anxiety (N=87; mean age, 10.51 years [SD=0.43]; 41% male) was utilized to test the stability of anxiety-related neural differences in the absence of treatment. Whole-brain regional activation changes (thresholded at p<0.001) were examined using task-based blood-oxygen-level-dependent response. RESULTS: Before treatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy comparison children across all task conditions. Fronto-parietal hyperactivation normalized over the course of treatment, whereas limbic responses remained elevated after treatment. In the at-risk sample, overlapping clusters emerged between regions showing stable associations with anxiety over time and regions showing treatment-related changes. CONCLUSIONS: Activation in fronto-parietal networks may normalize after CBT in unmedicated pediatric anxiety patients. Limbic regions may be less amenable to acute CBT effects. Findings from the at-risk sample suggest that treatment-related changes may not be attributed solely to the passage of time.

Resilience of the immune system in healthy young students to 30-hour sleep deprivation with psychological stress.

OBJECTIVE: Young adults often encounter sleep deprivation and stressful events. Both have been separately reported to modulate immunity, and occasionally they occur simultaneously. We assessed the combined effects of these conditions on immune competence in healthy students. METHODS: Twenty-three participants (mean age 24 years; SD 1.86; 14 females) were exposed to 30 h of sleep deprivation during which they conducted physiological, social and cognitive tasks. The control group consisted of 18 participants (mean age 23.67 years; SD 1.46; 11 females). All participants underwent cognitive and psychological evaluations at 10:00 AM, followed by blood and saliva collection, 3 days before sleep deprivation induction and on the morning following it. Immune/endocrine measures included blood counts of lymphocytes, granulocytes, monocytes and natural killer (NK) cells; levels of several cell surface markers; NK cytotoxicity; plasma levels of interleukin (IL)-6, IL-10, dehydroepiandrosterone and neuropeptide Y, and plasma and salivary cortisol levels. RESULTS: Although the experimental protocol significantly elevated state anxiety and psychological dissociation levels, no effects were evident in any of the immunological/endocrine indices. In contrast, expected sex differences in immune measures were found, including significantly higher NK cytotoxicity and monocyte counts in males, validating the integrity of the measurements. CONCLUSIONS: The findings suggest resilience of the immune system to a combined sleep deprivation and stressful exposure in young adults, while previous studies reported immune perturbations following either of these conditions separately. These apparent contradictions might reflect differences in the study design or in the methodology used for immunological assessments, including the time of sample collection, the combination of sleep deprivation with stress and our in vivo assessment of cytokine levels.

Context-dependent amygdala-prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces.

Irritability, defined as proneness to anger, is among the most common reasons youth are seen for psychiatric care. Youth with irritability demonstrate aberrant processing of anger-related stimuli; however, the neural mechanisms remain unknown. We applied a drift-diffusion model (DDM), a computational tool, to derive a latent behavioral metric of attentional bias to angry faces in youth with varying levels of irritability during functional magnetic resonance imaging (fMRI). We examined associations among irritability, task behavior using a DDM-based index for preferential allocation of attention to angry faces (i.e., extra-decisional time bias; Δt0), and amygdala context-dependent connectivity during the dot-probe task. Our transdiagnostic sample, enriched for irritability, included 351 youth (ages 8-18; M = 12.92 years, 51% male, with primary diagnoses of either attention deficit/hyperactivity disorder [ADHD], disruptive mood dysregulation disorder [DMDD], an anxiety disorder, or healthy controls). Models accounted for age, sex, in-scanner motion, and co-occurring symptoms of anxiety. Youth and parents rated youth's irritability using the Affective Reactivity Index. An fMRI dot-probe task was used to assess attention orienting to angry faces. In the angry-incongruent vs. angry-congruent contrast, amygdala connectivity with the bilateral inferior frontal gyrus (IFG), insula, caudate, and thalamus/pulvinar was modulated by irritability level and attention bias to angry faces, Δt0, all ts350 > 4.46, ps < 0.001. In youth with high irritability, elevated Δt0 was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated Δt0 was associated with stronger connectivity in those regions. No main effect emerged for irritability. As irritability is associated with reactive aggression, these results suggest a potential neural regulatory deficit in irritable youth who have elevated attention bias to angry cues.

Why superman can wait: cognitive self-transformation in the delay of gratification paradigm.

We examined middle-class Israeli preschoolers' cognitive self-transformation in the delay of gratification paradigm. In Study 1, 66 un-caped or Superman-caped preschoolers delayed gratification, half with instructions regarding Superman's delay-relevant qualities. Caped children delayed longer, especially when instructed regarding Superman's qualities. In Study 2 with 43 preschoolers, with the respective relevant superhero qualities emphasized (i.e., patient vs. impulsive), Superman-caped children tended to delay longer than Dash-caped children. In Study 3, 48 preschoolers delayed gratification after being instructed to pretend to be Superman or a child with the same patient qualities, or after watching a video of Superman, with or without pretend instructions. Invoking Superman led to longer delays and instructions regarding Superman's qualities tended to lead to longer delays than watching the Superman video. In accounting for the data, we differentiated cognitive transformations of the reward's consummatory value and cognitive transformations as basic intellectual processes.

Rationale and validation of a novel mobile application probing motor inhibition: Proof of concept of CALM-IT.

Identification of behavioral mechanisms underlying psychopathology is essential for the development of novel targeted therapeutics. However, this work relies on rigorous, time-intensive, clinic-based laboratory research, making it difficult to translate research paradigms into tools that can be used by clinicians in the community. The broad adoption of smartphone technology provides a promising opportunity to bridge the gap between the mechanisms identified in the laboratory and the clinical interventions targeting them in the community. The goal of the current study is to develop a developmentally appropriate, engaging, novel mobile application called CALM-IT that probes a narrow biologically informed process, inhibitory control. We aim to leverage the rigorous and robust methods traditionally used in laboratory settings to validate this novel mechanism-driven but easily disseminatable tool that can be used by clinicians to probe inhibitory control in the community. The development of CALM-IT has significant implications for the ability to screen for inhibitory control deficits in the community by both clinicians and researchers. By facilitating assessment of inhibitory control outside of the laboratory setting, researchers could have access to larger and more diverse samples. Additionally, in the clinical setting, CALM-IT represents a novel clinical screening measure that could be used to determine personalized courses of treatment based on the presence of inhibitory control deficits.

Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol.

INTRODUCTION: Irritability is defined as a tendency towards anger in response to frustration. Clinically, impairing irritability is a significant public health problem. There is a need for mechanism-based psychotherapies targeting severe irritability as it manifests in the context of disruptive mood dysregulation disorder (DMDD). This study protocol describes a randomised multiple baseline design testing the preliminary efficacy of a new treatment, exposure-based cognitive-behavioral therapy for severe irritability in youth, which also integrates components of parent management training. We will investigate associations of this intervention with primary clinical measures, as well as ecological momentary assessment measures. METHODS AND ANALYSIS: Forty youth will be enrolled. Participants, aged 8-17 years, must present at least one of two core symptoms of DMDD: abnormal mood or increased reactivity to negative emotional stimuli, with severe impairment in one domain (home, school, peers) and moderate in another, or moderate impairment in at least two domains. Each participant is randomised to a 2-week, 4-week or 6-week baseline observation period, followed by 12 active treatment sessions. Clinical ratings are conducted at baseline, biweekly (clinician), weekly (parent/child) throughout treatment, post-treatment, and 3-month and 6-month follow-up (clinician). Clinician ratings on the Affective Reactivity Index and Clinical Global Impressions-Improvement scale for DMDD are our primary outcome measures. Secondary outcome measures include parent and child reports of irritability. Post hoc additional symptom measures include clinician, parent and self-ratings of depression, anxiety and overall functional impairment. Prospective, digitally based event sampling of symptoms is acquired for a week pre-treatment, mid-treatment and post-treatment. Based on our pathophysiological model of irritability implicating frustrative non-reward, aberrant threat processing and instrumental learning, we probe these three brain-based targets using functional MRI paradigms to assess target engagement. ETHICS AND DISSEMINATION: The research project and all related materials were submitted and approved by the appropriate Institutional Review Board (IRB) of the National Institute of Mental Health (NIMH). TRIAL REGISTRATION NUMBERS: NCT02531893 and NCT00025935.

Cardiovascular reactivity as a measure of irritability in a transdiagnostic sample of youth: Preliminary associations.

OBJECTIVES: Irritability is a transdiagnostic symptom in developmental psychopathology, conceptualized as a low threshold for frustration and increased proneness to anger. While central to emotion regulation, there is a vital need for empirical studies to explore the relationship between irritability and underlying physiological mechanisms of cardiovascular arousal. METHODS: We examined the relationship between irritability and cardiovascular arousal (i.e., heart rate [HR] and heart rate variability [HRV]) in a transdiagnostic sample of 51 youth (M = 12.63 years, SD = 2.25; 62.7% male). Data was collected using the Empatica E4 during a laboratory stop-signal task. In addition, the impact of motion activity, age, medication, and sleep on cardiovascular responses was explored. RESULTS: Main findings showed that irritability was associated with increased HR and decreased HRV during task performance. CONCLUSIONS: Findings support the role of peripheral physiological dysregulation in youth with emotion regulation problems and suggest the potential use of available wearable consumer electronics as an objective measure of irritability and physiological arousal in a transdiagnostic sample of youth.

Attention bias to negative versus non-negative faces is related to negative affectivity in a transdiagnostic youth sample.

This study identified a shared pathophysiological mechanism of pediatric anxiety and irritability. Clinically, anxiety and irritability are common, co-occurring problems, both characterized by high-arousal negative affective states. Behaviorally, anxiety and irritability are associated with aberrant threat processing. To build on these findings, we examined eye-tracking measures of attention bias in relation to the unique and shared features of anxiety and irritability in a transdiagnostic sample of youth (n = 97, 58% female, Mage = 13.03, SDage = 2.82). We measured attention bias to negative versus non-negative emotional faces during a passive viewing task. We employed bifactor analysis to parse the unique and shared variance of anxiety and irritability symptoms from self- and parent-report questionnaires. Negative affectivity is the derived latent factor reflecting shared variance of anxiety and irritability. We found that higher negative affectivity was associated with looking longer at negative versus non-negative faces, reflecting a shared mechanism of anxiety and irritability. This finding suggests that modification of elevated attention to negative emotional faces may represent a common potential treatment target of anxiety and irritability.

Age Moderates Link Between Training Effects and Treatment Response to Attention Bias Modification Treatment for Social Anxiety Disorder.

Attention bias modification treatment (ABMT) aims to reduce anxiety symptoms via practice on computerized attention training tasks. Despite evidence of efficacy, clinical effects appear heterogeneous. More research on ABMT mechanisms and moderators of treatment response is needed. Age is one potentially important moderator, as developmental differences in training effects may impact response. We examined developmental links between ABMT training effects and response in social anxiety disorder (SAD). We pooled data from two randomized controlled trials in treatment-seeking youths and adults with SAD (N = 99) that used identical ABMT methods. We first characterized learning effects associated with the eight-session ABMT training protocol. We then tested whether learning magnitude predicted the clinical (change in SAD symptoms) and cognitive (change in attention bias) responses to treatment. Finally, we tested whether age moderated the association between ABMT learning and treatment response. Results indicate that ABMT was associated with an incremental learning curve during the protocol, and that learning improved with age. Age further moderated the association between learning gains during the ABMT protocol and subsequent reduction in self-reported SAD symptoms, such that this association was stronger with age. These effects were not evident in bias scores or clinician ratings. Finally, pre-treatment SAD symptoms and bias scores predicted ABMT learning gains. This study highlights the links among age, learning processes, and clinical response to ABMT. These insights may inform attempts to increase the clinical efficacy of ABMT for anxiety.

Attention and interpretation bias modification treatment for social anxiety disorder: A randomized clinical trial of efficacy and synergy.

BACKGROUND AND OBJECTIVES: Attention bias modification treatment (ABMT) and cognitive bias modification of interpretation (CBM-I) both have demonstrated efficacy in alleviating social anxiety, but how they compare with each other, their combination, and with a combined control condition has not been studied. We examined their relative and combined efficacy compared to control conditions in a randomized controlled trial (RCT). METHODS: Ninety-five adults diagnosed with social anxiety disorder (SAD), were randomly allocated to 4 groups: ABMT + CBM-I control (hereafter ABMT; n = 23), CBM-I + ABMT control (hereafter CBM-I; n = 24), combined ABMT + CBM-I (n = 23), and combined control (n = 25). Treatment included eight sessions over four weeks. Clinician-rated and self-reported measures of social anxiety symptoms, functional impairment, and threat-related attention and interpretive biases were evaluated at baseline, post-treatment, and 3-month follow-up. RESULTS: ABMT yielded greater symptom reduction as measured by both clinician-ratings (Cohen's ds = 0.57-0.70) and self-reports (ds = 0.70-0.85) compared with the CBM-I, the combined ABMT + CBM-I, and the combined control conditions. Neither of the other conditions demonstrated superior symptom change compared to the control condition. No group differences were found for functioning or cognitive biases measures. LIMITATIONS: Limitations mainly include the mix of active and control treatments applied across the different groups. Therefore, the net effect of each of the treatments by itself could not be clearly tested. CONCLUSIONS: Results suggest superiority of ABMT compared to CBM-I and their combination in terms of symptom reduction. Possible interpretations and methodological issues underlying the observed findings are discussed.