Pediatric Irritability Research Articles

The Validity of a Frustration Paradigm to Assess the Effect of Frustration on Cognitive Control in School-Age Children

Irritability refers to a proneness for anger, and is a symptom of internalizing and externalizing psychopathology. Since irritability is associated with significant cross-sectional and longitudinal impairments, research on the behavioral and neural correlates of pediatric irritability in populations at risk for significant irritability is of paramount importance. Irritability can be assessed in the laboratory using behavioral paradigms that elicit frustration. Few behavioral frustration paradigms have been designed to measure the effects of frustration on cognitive control. Therefore, the goal of the present study was to validate a behavioral frustration paradigm for use in school-age children which addressed some of the limitations of prior research. Participants included children, ages 8–12 years, who were either typically developing (TD; n = 38) or diagnosed with attention-deficit/hyperactivity disorder (ADHD; n = 67), which provided a sample of children with a range of baseline irritability. All participants completed the Frustration Go/No-Go (GNG) task, and self-reported irritability was assessed using the Affective Reactivity Index. Results showed that across participants, self-reported frustration, commission error rate, and tau all increased with the addition of frustration, with similar effect sizes in ADHD and TD groups. Further, self-reported irritability, moreso than ADHD symptoms, predicted changes in self-reported frustration during the task. Together, these results support the construct validity of the Frustration GNG task as a means of assessing the effect of frustration on cognitive control. Clinical applications and future directions are discussed.

Exposure therapy for pediatric irritability: Theory and potential mechanisms

Pediatric irritability is prevalent and impairing, yet little is known about its pathophysiology and treatment. In this article, we build on our and others' previous work to posit core mechanisms of irritability operating across the brain, behavior, and environment. Specifically, we propose proximal processes that surround the symptomatology of irritability and are potential targets for an exposure-based cognitive-behavioral therapy (CBT) for irritability that our group has developed. The heart of this model focuses on neurocognitive processes: youth's encoding of nonreward and threat stimuli, which involves prediction error signaling in the brain, and cognitive control in the context of frustration. Alterations in these processes are theorized to be central to chronic, severe irritability. Environmental responses to youth's symptom expression are also examined. Exposure-based CBT for irritability utilizes controlled, in vivo exposure to nonreward and threat stimuli with the aim to engage cognitive control and target top-down regulation of frustration. This intervention integrates selected parent management training techniques to target symptom reinforcement processes. Continued pathophysiological and treatment studies of irritability will not only refine our emerging understanding of the phenotype, but also inform broader questions on the brain and behavioral mechanisms of CBT efficacy.

57. Unique Neural Associations With Pediatric Irritability During Frustration and Threat Orienting

Irritability, defined as increased proneness to anger relative to peers, is extremely common in youth, yet there are few evidence-based treatments. Elucidating the relevant circuitry dysfunction would facilitate the development of mechanism-based interventions. We have posited two core deficits in irritability: aberrant responses to frustration (i.e., blocked goal attainment) and aberrant approach responses to threat. We present data from two fMRI studies, a frustration task and a threat orienting task.

A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth

Comorbidity is ubiquitous in psychiatry, but it is unclear how to differentiate neural mechanisms of co-occurring symptoms. Pediatric irritability and anxiety symptoms are prevalent and frequently co-occur. Threat orienting is pertinent to both phenotypes and is an ideal context in which to examine their unique and common neural mechanisms. To decompose the unique and shared variances of pediatric irritability and anxiety symptoms and to determine neural correlates of these differentiated phenotypes during threat orienting. This investigation was a cross-sectional functional magnetic resonance imaging study. The setting was a research clinic at the National Institute of Mental Health. Participants were youth aged 8 to 18 years spanning multiple diagnostic categories (141 youth with disruptive mood dysregulation disorder, anxiety disorder, and/or attention-deficit/hyperactivity disorder and 56 healthy youth). This combination provided wide variation in levels of irritability and anxiety symptoms. Data were acquired between June 30, 2012, and June 28, 2016. Participants and parents rated youth's irritability on the Affective Reactivity Index and anxiety on the Screen for Child Anxiety Related Emotional Disorders. Bifactor analysis decomposed the unique and shared variances. A functional magnetic resonance imaging dot-probe task assessed attention orienting to angry (ie, threat) vs neutral faces. Whole-brain analyses examined associations between the bifactor-derived phenotypes and both neural activity and amygdala functional connectivity. Among 197 participants included in the final analysis, the mean (SD) age was 13.1 (2.7) years, and 91 (46.2%) were female. The best-fit bifactor model (Comparative Fit Index, 0.959; Root Mean Square Error of Approximation, 0.066) included unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity. When the task required attention away from threat, higher parent-reported irritability was associated with increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule (t189≥4.15 for all, P < .001 for all). In contrast, higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus (t189≤-4.19 for all, P < .001 for all). These distinctive neural correlates did not emerge using a diagnostic approach. A latent variable approach to parsing co-occurring symptom dimensions revealed a novel double dissociation. During orientation away from threat, only irritability was associated with neural activity, whereas only anxiety was associated with amygdala connectivity. Despite the challenges of symptom co-occurrence for clinical neuroscience, data-driven phenotyping may facilitate a path forward.

4.50 Face Emotion Labeling in Pediatric Irritability: Behavioral and Neural Correlates

4.50 Face Emotion Labeling in Pediatric Irritability: Behavioral and Neural Correlates

249. Shared and Unique Neural Correlates of Threat Processing in Pediatric Irritability and Anxiety

249. Shared and Unique Neural Correlates of Threat Processing in Pediatric Irritability and Anxiety

Where pediatric irritability research is now, and where it needs to go

Irritability, a common problem in youth, is an “increased propensity to exhibit increased anger relative to one's peers,” writes Ellen Leibenluft, M.D., senior investigator and chief of the Section on Mood Dysregulation and Neuroscience and co‐branch chief of the Emotion and Development Branch at the National Institute of Mental Health Intramural Research Program.

Table of Contents

AbstractUnderstanding and Treating Trichotillomania: Not Just a Benign HabitDSM‐5 and Pediatric Irritability: Acknowledging the Elephant in the RoomChildhood‐Onset BPD Linked With Poor Adult OutcomeChildhood Obesity and BullyingPsychosocial Risk Factors Associated With CyberbullyingSurvey Looks at Who Treats Child Insomnia With MedicationAdolescent Drug‐Related ER Visits and Suicide AttemptsCurrent DSM‐IV Criteria for a Manic EpisodeCollege Drinking: Listing of Top 20 “Party Schools” Called Into Question