Concurrent and longitudinal neurostructural correlates of irritability in children.

Irritability, or an increased proneness to frustration and anger, is common in youth; however, few studies have examined neurostructural correlates of irritability in children. The purpose of the current study was to examine concurrent and longitudinal associations between brain structure and irritability in a large sample of 9-10-year-old children. Participants included 10,647 children from the Adolescent Brain Cognitive Developmentsm Study (ABCD Study®). We related a latent irritability factor to gray matter volume, cortical thickness, and surface area in 68 cortical regions and to gray matter volume in 19 subcortical regions using structural equation modeling. Multiple comparisons were adjusted for using the false discovery rate (FDR). After controlling for age, sex, race/ethnicity, scanner model, parent's highest level of education, medication use, and total intracranial volume, irritability was associated with smaller volumes in primarily temporal and parietal regions at baseline. Longitudinal analyses showed that baseline gray matter volume did not predict irritability symptoms at the 3rd-year follow-up. No significant associations were found for cortical thickness or surface area. The current study demonstrates inverse associations between irritability and volume in regions implicated in emotional processing/social cognition, attention allocation, and movement/perception. We advance prior research by demonstrating that neurostructural differences associated with irritability are already apparent by age 9-10 years, extending this work to children and supporting theories positing socioemotional deficits as a key feature of irritability.

Prevalence and correlates of irritability among U.S. adults.

This study aimed to characterize the prevalence of irritability among U.S. adults, and the extent to which it co-occurs with major depressive and anxious symptoms. A non-probability internet survey of individuals 18 and older in 50 U.S. states and the District of Columbia was conducted between November 2, 2023, and January 8, 2024. Regression models with survey weighting were used to examine associations between the Brief Irritability Test (BITe5) and sociodemographic and clinical features. The survey cohort included 42,739 individuals, mean age 46.0 (SD 17.0) years; 25,001 (58.5%) identified as women, 17,281 (40.4%) as men, and 457 (1.1%) as nonbinary. A total of 1218(2.8%) identified as Asian American, 5971 (14.0%) as Black, 5348 (12.5%) as Hispanic, 1775 (4.2%) as another race, and 28,427 (66.5%) as white. Mean irritability score was 13.6 (SD 5.6) on a scale from 5 to 30. In linear regression models, irritability was greater among respondents who were female, younger, had lower levels of education, and lower household income. Greater irritability was associated with likelihood of thoughts of suicide in logistic regression models adjusted for sociodemographic features (OR 1.23, 95% CI 1.22-1.24). Among 1979 individuals without thoughts of suicide on the initial survey assessed for such thoughts on a subsequent survey, greater irritability was also associated with greater likelihood of thoughts of suicide being present (adjusted OR 1.17, 95% CI 1.12-1.23). The prevalence of irritability and its association with thoughts of suicide suggests the need to better understand its implications among adults outside of acute mood episodes.

Neural mechanisms of inhibitory control in preadolescent irritability: Insights from the ABCD study.

OBJECTIVE: Elevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.e., preadolescence). METHOD: Functional MRI data from 5380 preadolescents (age M=9.97 years, SD=0.62) in the baseline Adolescent Brain and Cognitive Development (ABCD) Study were analyzed. Parents reported on their preadolescent's irritability. The stop signal task (SST) was leveraged to probe successful and failed inhibitory control. Activation and functional connectivity with amygdala, ventral striatum, and prefrontal seed regions were calculated during the SST and used in whole brain and region of interest (ROI) group-level analyses evaluating irritability effects. RESULTS: Preadolescents with higher levels of irritability displayed decreases in functional connectivity among amygdala, ventral striatum, and prefrontal cortex regions during both successful and failed inhibitory control conditions. These results remained after adjusting for co-occurring anxiety, depression, and attention-deficit/hyperactivity symptoms. CONCLUSIONS: Findings suggest neural aberrations in inhibitory control play a role in the pathophysiology of preadolescent irritability and associations are not merely due to co-occurring symptoms. Neural mechanisms of inhibitory control associated with irritability may provide novel intervention targets.

Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.

Irritability, a state of excessive reactivity to negative emotional stimuli, is common in individuals with autism spectrum disorder (ASD). Although it has a significant negative impact of patients' disease severity and quality of life, the neural mechanisms underlying irritability in ASD remain largely unclear. We have previously demonstrated that male mice lacking the Coiled-coil and C2 domain containing 1a (Cc2d1a) in forebrain excitatory neurons recapitulate numerous ASD-like behavioral phenotypes, including impaired social behaviors and pronounced repetitive behaviors. Here, using the bottle-brush test (BBT) to trigger and evaluate aggressive and defensive responses, we show that Cc2d1a deletion increases irritability-like behavior in male but not female mice, which is correlated with reduced number of oxytocin (OXT)-expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Intranasal OXT administration or chemogenetic activation of OXT neurons in the PVN rescues irritability-like behavior in Cc2d1a conditional knockout (cKO) mice. Administration of a selective melanocortin receptor 4 agonist, RO27-3225, which potentiates endogenous OXT release, also alleviates irritability-like behavior in Cc2d1a cKO mice, an effect blocked by a specific OXT receptor antagonist, L-368,899. We additionally identify a projection connecting the posterior ventral segment of the medial amygdala (MeApv) and ventromedial nucleus of the ventromedial hypothalamus (VMHvl) for governing irritability-like behavior during the BBT. Chemogenetic suppression of the MeApv-VMHvl pathway alleviates irritability-like behavior in Cc2d1a cKO mice. Together, our study uncovers dysregulation of OXT system in irritability-like behavior in Cc2d1a cKO mice during the BBT and provide translatable insights into the development of OXT-based therapeutics for clinical interventions.

An Expanded Conceptual Framework for Understanding Irritability in Childhood: The Role of Cognitive Control Processes.

Children prone to irritability experience significant functional impairments and internalising and externalising problems. Contemporary models have sought to elucidate the underlying mechanisms in irritability, such as aberrant threat and reward biases to improve interventions. However, the cognitive control processes that underlie threat (e.g., attention towards threats) and reward (e.g., attention towards reward-related cues) biases and the factors which influence the differential activation of positive and negative valence systems and thus leading to maladaptive activation of cognitive control processes (i.e., proactive and reactive control) are unclear. Thus, we aim to integrate extant theoretical and empirical research to elucidate the cognitive control processes underlying threat and reward processing that contribute to irritability in middle childhood and provide a guiding framework for future research and treatment. We propose an expanded conceptual framework of irritability that includes broad intraindividual and environmental vulnerability factors and propose proximal 'setting' factors that activate the negative valence and positive valence systems and proactive and reactive cognitive control processes which underpin the expression and progression of irritability. We consider the implications of this expanded conceptualisation of irritability and provide suggestions for future research.

Associations between trauma exposure and irritability within the family unit: a network approach.

BACKGROUND: Pediatric irritability is a pervasive psychiatric symptom, yet its etiology remains elusive. While trauma exposure may contribute to the development of irritability, empirical research is limited. This study examined the prevalence of irritability among trauma-exposed children, identified factors that differentiate trauma-exposed children with and without irritability, and employed a network analysis to uncover associations between irritability and trauma exposure in the family unit. METHODS: Sample included 676 children (56.3% male, mean age = 9.67 ± 3.7 years) and their parents referred by the Connecticut Department of Children and Families to Fathers for Change - a psychotherapy intervention designed to reduce intimate partner violence (IPV) and child maltreatment. Child's trauma exposure, post-traumatic stress disorder (PTSD) symptoms, and irritability were assessed pre-intervention using self- and caregiver-report. Parents self-reported their childhood and adulthood trauma exposures, PTSD symptoms, irritability, psychopathology, and IPV. RESULTS: Across caregiver- and child-reports, 16%-17% of children exhibited irritability. Irritable children experienced greater trauma exposure, interpersonal violence, emotional abuse, and PTSD severity. They had caregivers, particularly mothers, with greater trauma histories, IPV, and psychopathology. Network analysis revealed 10 nodes directly correlated to child's irritability including child's PTSD severity, parental IPV (specifically psychological violence), and parental psychopathology. CONCLUSIONS: Results provide initial empirical evidence that pediatric irritability is linked to trauma exposure, suggesting trauma histories be considered in the diagnosis and treatment of irritability. Interventions addressing caregiver trauma, IPV, and psychopathology may ameliorate pediatric irritability. Future studies could benefit from adopting network approaches with longitudinal or time series data to elucidate causality and points of intervention.

The utility of the irritability scale in Huntington's disease patients with evidence of irritability or aggression.

INTRODUCTION: Irritability, a common neuropsychiatric symptom in Huntington's disease (HD), lacks a standardized measurement. The Irritability Scale (IS), tailored for HD, has patient and informant versions, but variable interrater agreement has been reported frequently in previous studies. To enhance the clinical utility of the IS, this study aimed to identify the most reliable components estimating the underlying construct and develop a shortened version for time-limited contexts. METHODS: Participant and informant/observer concordance and the relationship of individual items to the complete IS scale were assessed. The short-form (SF) items were selected based on interrater agreement, exploratory factor analysis (EFA), and Item Response Theory (IRT) analysis results. Pair-wise correlation and covariance models were used to examine how SF predicted total IS score in 106 participants from the STAIR (Safety, Tolerability, and Activity of SRX246 in Irritable Subjects with Huntington's Disease) trial. Item Response Theory (IRT) analysis was used to evaluate the range and function of the selected items. RESULTS: IS interrater agreement was statistically significant (r = 0.33, p = .001). In combination with EFA factors and IRT analyses, five items were identified that showed good reliability and performance in differentiating levels of irritability. CONCLUSION: The proposed 5-item SF IS provided a reliable measure of the full scale and may be less burdensome for use in a clinical setting.

Weekly links among irritability and suicidal thoughts and behaviors in high-risk youth.

BACKGROUND: Previous studies demonstrate a link between irritability and suicidal thoughts and behaviors (STBs) in youth samples. However, they have mostly assessed irritability in community samples and as a largely dispositional (i.e. trait-like) construct. Thus, it remains unclear to what extent links between irritability and STBs reflect within-person processes of elevated risk in clinically meaningful time periods. METHODS: The present study used clinical data from 689 adolescents aged 12-19 years attending a total of 6,128 visits at a specialty Intensive Outpatient Program for depressed and suicidal youth to examine patterns in weekly assessments of irritability and STBs throughout treatment, including associations among trends and fluctuations departing from these trends via multilevel structural equation modeling. Youth completed self-report measures of irritability, depression, and STBs weekly as part of standard IOP clinical care. RESULTS: Overall, two-thirds of variance in weekly irritable mood was accounted for by between-person differences and the remaining portion by weekly fluctuations. After controlling for depression, during weeks when youth were more irritable they experienced increased STBs. Rates of change in irritability and STBs tended to track together at early stages of treatment, but these effects were generally accounted for by depression severity. CONCLUSIONS: Our results suggest that although changes in STBs are best accounted for by depression, irritability can be understood as a specific, proximal risk factor for youth STBs that exacerbates youth STBs in clinically informative timeframes above and beyond depression.

How are irritability and anhedonia symptoms linked? A network approach.

BACKGROUND: Anhedonia and irritability are two prevalent symptoms of major depressive disorder (MDD) that predict greater depression severity and poor outcomes, including suicidality. Although both symptoms have been proposed to result from paradoxical reward processing dysfunctions, the interactions between these symptoms remain unclear. Anhedonia is a multifaceted symptom reflecting impairments in multiple dimensions of reward processing (e.g., pleasure, desire, motivation, and effort) across distinct reward types (e.g., food, sensory experiences, social activities, hobbies) that may differentially interact with irritability. This study investigated the complex associations between anhedonia and irritability using network analysis. METHOD: Participants (N = 448, Mage = 33.29, SD = 14.58) reported their symptoms of irritability on the Brief Irritability Test (Holtzman et al., 2015) and anhedonia (i.e., pleasure, desire, motivation, and effort dimensions across four reward types) on the Dimensional Anhedonia Rating Scale (Rizvi et al., 2015). A regularized Gaussian Graphical Model was built to estimate the network structure between items. RESULTS: Irritability was negatively related to willingness to expand effort to obtain food/drinks (estimate = -0.18), social activities (-0.13), and hobbies (-0.12) rewards. Irritability was positively associated with a desire for food/drinks (0.12). LIMITATIONS: Only a small proportion (5.8%) of our sample was clinical and the study design was cross-sectional. CONCLUSION: A specific link between irritability and the effort dimension of the hedonic response across three reward types was identified. Investigating effort expenditure deficits with experimental paradigms may help us understand the mechanisms underlying the comorbidity between irritability and anhedonia in the context of MDD.

Early Predictors and Concurrent Correlates of Tonic and Phasic Irritability in Adolescence.

Irritability is a common presenting problem in youth mental health settings that is thought to include two components: tonic (e.g., irritable, touchy mood) and phasic (e.g., temper outbursts), each with unique correlates and outcomes, including later internalizing and externalizing problems, respectively. However, we are unaware of any studies of early predictors of tonic and phasic irritability. We utilized data from a longitudinal study of a community sample of 3-year-old children followed to age 15 (n = 444). We conducted confirmatory factor analysis (CFA) of items from several self-report irritability measures at age 15, including the Affective Reactivity Index, the International Personality Item Pool, the Schedule for Non-Adaptive and Adaptive Personality Youth Version, and the Child Depression Inventory, and examined their early childhood predictors. The CFA identified dimensions consistent with tonic and phasic irritability. Tonic irritability at age 15 was uniquely associated with concurrent internalizing disorders and suicidal behavior while phasic irritability was uniquely associated with concurrent externalizing disorders. When adolescent tonic and phasic irritability were examined together, female sex and parental depressive and substance use disorders at age 3 uniquely predicted adolescent tonic irritability. Additionally, male sex, less parental education, greater laboratory-observed anger and impulsivity, ODD symptoms, higher irritability, and no parental substance use history at age 3 uniquely predicted adolescent phasic irritability. Youth-reported tonic and phasic irritability at age 15 appear to be distinguishable constructs with distinct concurrent correlates and early antecedents. Findings have important implications for research on the etiology of irritability and developing effective treatments.

Irritability in Youths: A Critical Integrative Review.

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.

Neural Responses to Intranasal Oxytocin in Youths With Severe Irritability.

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.

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.

Novel Assessment of the Impact of Irritability on Physiological and Psychological Frustration Responses in Adolescents.

OBJECTIVE: Irritability, typically defined as a proneness to anger, particularly in response to frustration, falls at the intersection of emotion and disruptive behavior. Despite well-defined translational models, there are few convergent findings regarding the pathophysiology of irritability. Most studies utilize computer-based tasks to examine neural responses to frustration, with little work examining stress-related responding to frustration in social contexts. The present study is the first to utilize the novel Frustration Social Stressor for Adolescents (FSS-A) to examine associations between adolescent irritability and psychological and physiological responses to frustration. METHOD: The FSS-A was completed by a predominantly male, racially, ethnically, and socioeconomically diverse sample of 64 12- to 17-year-olds, who were originally recruited as children with varying levels of irritability. Current irritability was assessed using the Multidimensional Assessment Profiles-Temper Loss scale (MAP-TL-Youth). Adolescents rated state anger and anxiety before and after the FSS-A, and usable salivary cortisol data were collected from 43 participants. RESULTS: Higher MAP-TL-Youth scores were associated with greater increases in anger during the FSS-A, but not increases in anxiety, or alterations in cortisol. Pre-task state anger negatively predicted the slope of the rise in cortisol observed in anticipation of the FSS-A. CONCLUSIONS: Results provide support for unique associations between adolescent irritability and anger during, and in anticipation of, frustrating social interactions. Such findings lay a foundation for future work aimed at informing physiological models and intervention targets.

Is irritability multidimensional: Psychometrics of The Irritability and Dysregulation of Emotion Scale (TIDES-13).

Irritability is a common, impairing, and potentially multifaceted manifestation of psychopathology. We designed The Irritability and Dysregulation of Emotion Scale (TIDES-13) to determine whether various expressions of irritability in children and youth form multiple subdimensions with distinct correlates. We administered parent-report (n = 3875, mean age = 8.9) and youth self-report (n = 579, mean age = 15.1) versions of TIDES-13 in a population and community-based sample. We conducted exploratory/confirmatory factor analyses and regression analyses to examine the dimensionality of TIDES-13 and the associations of the scale with age, gender, anxiety, depression, ODD, ADHD traits, and the Affective Reactivity Index (ARI). A higher-order model with a global irritability dimension and four subdimensions, including proneness to anger (PA), internalized negative emotional reactivity (iNER), externalized negative emotional reactivity (eNER), and reactive aggression (RA), showed good to excellent fit in both parent-report and self-report. The global irritability dimension showed excellent internal reliability (⍵Total; parent-report = 0.97, ⍵Total; self-report = 0.95), explained a majority of the item variance (⍵Hierarchical; parent-report = 0.94, ⍵Hierarchical; self-report = 0.90), and was moderately correlated with the ARI (rparent = 0.68, rself = 0.77). Subdimensions PA, eNER, and RA were negatively associated with age in males, whereas iNER was positively associated with age in females. Traits of ODD and ADHD were associated primarily with the global irritability dimension, whereas iNER was strongly associated with anxiety and depression traits over and above the global irritability dimension. Our results support a unidimensional interpretation of irritability in a population sample. However, limited evidence of specific behavioral, age, and sex correlates with particular irritability subdimensions may warrant further investigation.

Cross-Sectional and Longitudinal Relations Among Irritability, Attention-Deficit/Hyperactivity Disorder Symptoms, and Inhibitory Control.

OBJECTIVE: Irritability and attention-deficit/hyperactivity disorder (ADHD) symptoms frequently co-occur in youth. Although ADHD has been associated with inhibitory control deficits, the literature on irritability and inhibitory control is mixed. Examining how irritability, ADHD symptoms, and inhibitory control interrelate both cross-sectionally and longitudinally across development could shed light on common and distinct mechanisms of youth psychopathology. METHOD: We utilized a cross-lagged panel model with data from 2 time points (at ages 10 and 12 years) of the Adolescent Brain and Cognitive Development (ABCD) Study (N = 7,444, or ∼63% of the baseline sample with full data at each time point) to test cross-sectional and longitudinal associations among parent-reported irritability and ADHD symptoms and behaviorally assessed inhibitory control. This was performed separately across discovery and replication subsamples, each n = 3,722. RESULTS: As expected, irritability and ADHD symptoms exhibited strong cross-sectional and reciprocal cross-lagged associations. Higher ADHD symptoms at age 10 years were associated concurrently with poorer inhibitory control and predicted poorer inhibitory control at age 12. Contrary to predictions, inhibitory control was not significantly associated with irritability cross-sectionally, nor was it predictive of later irritability or ADHD symptoms. CONCLUSION: These findings highlight strong links between irritability and ADHD. Although inhibitory control deficits were linked to ADHD and predictive of its symptom course, inhibitory control had no significant associations with irritability. Future research should investigate other candidate mechanisms of the co-occurrence of irritability and ADHD symptoms and predictors of their developmental trajectories. PLAIN LANGUAGE SUMMARY: This study investigated how irritability, ADHD symptoms, and inhibitory control interrelate both cross-sectionally and longitudinally in a sample of youth from the Adolescent Brain and Cognitive Development (ABCD) Study (N = 7,444). Results indicate that irritability and ADHD symptoms exhibit strong reciprocal predictive relationships; however, inhibitory control does not predict later irritability or ADHD, though ADHD symptoms predicted later inhibitory control deficits. These findings corroborate the predictive relations between irritability and ADHD over development and highlight the need for continued exploration of mechanisms underlying their co-occurrence.

Editorial: Neuropsychological Correlates of Irritability Accompanying Symptoms of Attention-Deficit/Hyperactivity Disorder: Clues and Pitfalls.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders and is characterized by developmentally inappropriate, pervasive, and impairing symptoms of inattention and/or hyperactivity/impulsivity.1 Although not listed among the core symptoms, irritability, reduced tolerance to frustration, and labile mood are considered features associated with ADHD.1,2 Irritability refers to a tendency to get angry quickly and/or easily at a lower threshold of frustration and respond disproportionately to triggers.3 Almost two-thirds of youth with ADHD may display impairing irritability, while rates of ADHD may be elevated among youth with clinically significant irritability.2 Irritability and impulsivity are thought to share neurobiological mechanisms that may overlap with executive and self-regulatory functions such as inhibitory control.3-5 The nature and developmental stability of these associations are still debated. Areas of controversy include the role of emotion regulation problems in positive vs negative emotions for impairment6; relations between those problems and risk-taking behavior, hyperactive-impulsive symptoms, and disruptive behavior problems2-5; and the nature of emotion regulation problems (ie, as core symptoms, as a feature of a variant of ADHD, or as a characteristic of specific comorbidities such as depression).2.

Parent and Teacher Ratings of Tonic and Phasic Irritability in a Clinical Sample.

Research on tonic (persistently angry or grumpy mood) and phasic (temper tantrums/outbursts) irritability in youth has utilized community samples and information from parents and youth. We examined whether tonic and phasic irritability are empirically distinguishable and have similar correlates using teacher, in addition to parent, reports in a clinical sample of children and adolescents. The sample included youth aged 5-18 evaluated at a university outpatient clinic, with complete information from 2481 parents and 2449 teachers. We conducted confirmatory factor analysis (CFA) using items from several parent- and teacher-report inventories and examined concurrent associations with psychopathology and functioning. The CFA supported a two-factor model consistent with tonic and phasic irritability in both parent- and teacher-reports. Parent-reported tonic irritability was associated with higher rates of depression and anxiety disorders, suicidality, and antidepressant medication use. Teacher-reported tonic irritability was associated with elevated rates of depression and antidepressant use. Both parent- and teacher-reported phasic irritability were linked to higher rates of ADHD combined type, oppositional defiant/conduct disorders, and referral for rages. Parent- and teacher-reported tonic and phasic irritability were all associated with impaired social functioning. Parents and teachers can distinguish tonic and phasic irritability, which are associated with internalizing and externalizing problems, respectively. Findings were generally consistent across informants, and with prior studies using community samples.

Phasic Versus Tonic Irritability and Associations with Family Accommodation Among Youth with Selective Mutism: A Latent Profile Analysis.

Clinical presentations of selective mutism (SM) vary widely across affected youth. Although studies have explored general externalizing problems in youth with SM, research has not specifically examined patterns of irritability. Relatedly, research has not considered how affected families differentially accommodate the anxiety of youth with SM as a function of the child's temper outbursts (i.e., phasic irritability) and general angry mood (i.e., tonic irritability). Data were drawn from a sample of treatment-seeking children and adolescents with a primary diagnosis of selective mutism (N = 152; Mean age = 6.12 years; 67.11% female), and their caregivers. Latent profile analysis (LPA) was used to identify distinct profiles in SM youth that were characterized by varying levels of phasic and/or tonic irritability. Analyses further examined whether these different profiles were associated with different levels of family accommodation and global impairment. LPA identified 5 profiles: SM with No irritability, SM with Low Phasic Irritability, SM with High Phasic Irritability, SM with High Phasic and Moderate Tonic Irritability, and SM with High Phasic and High Tonic Irritability. Patterns of family accommodation and global impairment were highest among youth belonging to profiles characterized by high phasic irritability. Findings highlight separable patterns of irritability across youth with SM, with phasic irritability (i.e., temper outbursts) appearing particularly linked with increased family accommodation and overall global impairment. Assessing phasic irritability is critical for optimizing treatment in youth with SM and can be useful for flagging possible patterns of family accommodation contributing to overall impairment.

Executive function in children with disruptive mood dysregulation disorder compared to attention-deficit/hyperactivity disorder and oppositional defiant disorder, and in children with different irritability levels.

Addressing current challenges in research on disruptive mood dysregulation disorder (DMDD), this study aims to compare executive function in children with DMDD, children with attention-deficit/hyperactivity disorder (ADHD), and children with oppositional defiant disorder (ODD). We also explore associations between irritability, a key DMDD characteristic, and executive function in a clinical sample regardless of diagnosis. Our sample include children (6-12 years) referred to child psychiatric clinics. Measures of daily-life (parent-reported questionnaire) and performance-based (neuropsychological tasks) executive function were applied. Identifying diagnoses, clinicians administered a standardized semi-structured diagnostic interview with parents. Irritability was assessed by parent-report. First, we compared executive function in DMDD (without ADHD/ODD), ADHD (without DMDD/ODD), ODD (without DMDD/ADHD) and DMDD + ADHD (without ODD). Second, we analyzed associations between executive function and irritability using the total sample. In daily life, children with DMDD showed clinically elevated and significantly worse emotion control scores compared to children with ADHD, and clinically elevated scores on cognitive flexibility compared to norm scores. Children with DMDD had significantly less working memory problems than those with ADHD. No differences were found between DMDD and ODD. Increased irritability was positively associated with emotional dyscontrol and cognitive inflexibility. For performance-based executive function, no diagnostic differences or associations with irritability were observed. We discuss how, in daily life, children with high irritability-levels get overwhelmed by feelings without accompanying regulatory capacities.