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.

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.

An investigation of the neural basis of anger attributions in irritable youth.

Neurocognitive models of pediatric irritability suggest a prominent role of anger; however, few studies have investigated anger-related biases and their neural correlates. Resting state functional connectivity (rsFC) of the amygdala was examined in relation to anger attribution bias (AAB) in a sample of young children (5-9 years old; N = 60; 55% White, 26.7% Hispanic) with clinically significant irritability characterized by impairing emotional outbursts (IEOs). Children completed a resting state functional magnetic resonance imaging scan as well as the assessment of children's emotional skills (ACES), which yields three measures of AAB in the context of social situations, social behaviors, and facial expressions. ACES scores were entered into a general linear model to examine associations with rsFC of the bilateral amygdalae. Children with IEOs exhibited significant biases in attributing anger to others across all three ACES domains. Greater biases toward attributing anger in social situations were associated with reduced rsFC of the bilateral amygdalae with the fusiform/lingual gyri and lateral occipital cortex. Alternatively, greater biases toward attributing anger to facial expressions positively predicted right amygdala-precuneus rsFC. Greater bias toward attributing anger to others based on their behaviors was associated with heightened rsFC of the right amygdala with the left middle frontal gyrus. Findings extend previous work implicating functional connections among regions of default mode and frontoparietal networks in pediatric irritability. Longitudinal studies are needed to further investigate the putative role of AAB in the etiology and long-term outcomes of pediatric irritability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications.

OBJECTIVES: Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. METHODS: The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n = 340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). RESULTS: Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. CONCLUSION: Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.

Review: Defining Positive Emotion Dysregulation: Integrating Temperamental and Clinical Perspectives.

OBJECTIVE: Although emotion dysregulation has been defined as a maladaptive process of emotional experiences, there is no specific reference to the emotional valence of the dysregulation. To date, child psychiatry has focused primarily on dysregulation of negative affect. Here, we suggest that positive emotion dysregulation requires additional clinical and research attention. METHOD: First, we present a developmental approach to the study of positive emotion regulation within a temperament framework. Second, we describe emerging research findings regarding dysregulation of positive emotion in early childhood. Third, we integrate neuroscientific approaches to positive emotion regulation and introduce a framework for future investigations and clinical applications. RESULTS: Dysregulation in positive affect can be examined from temperamental, developmental, clinical, and neuroscientific perspectives. Both temperamental surgency, which includes positive affect, and the proposed clinical extension, excitability, are associated with increased risk of externalizing symptoms and clinical impairment in youth. CONCLUSION: Studying the role of both temperamental surgency and clinically impairing positive affect, or excitability, in developmental psychopathology will help to elucidate the full spectrum of emotion dysregulation and to clarify the neural basis of dysregulation. A more comprehensive conceptualization of positively valanced emotion dysregulation will provide a more nuanced understanding of developmental risk and potential targets for intervention. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science.

Mediating role of the default mode network on parental acceptance/warmth and psychopathology in youth.

Humans are reliant on their caregivers for an extended period of time, offering numerous opportunities for environmental factors, such as parental attitudes and behaviors, to impact brain development. The default mode network is a neural system encompassing the medial prefrontal cortex, posterior cingulate cortex, precuneus, and temporo-parietal junction, which is implicated in aspects of cognition and psychopathology. Delayed default mode network maturation in children and adolescents has been associated with greater general dimensional psychopathology, and positive parenting behaviors have been suggested to serve as protective mechanisms against atypical default mode network development. The current study aimed to extend the existing research by examining whether within- default mode network resting-state functional connectivity would mediate the relation between parental acceptance/warmth and youth psychopathology. Data from the Adolescent Brain and Cognitive Development study, which included a community sample of 9,366 children ages 8.9-10.9 years, were analyzed to test this prediction. Results demonstrated a significant mediation, where greater parental acceptance/warmth predicted greater within- default mode network resting-state functional connectivity, which in turn predicted lower externalizing, but not internalizing symptoms, at baseline and 1-year later. Our study provides preliminary support for the notion that positive parenting behaviors may reduce the risk for psychopathology in youth through their influence on the default mode network.

Measuring Emotion Dysregulation in Children With Attention-Deficit/Hyperactivity Disorder: Revisiting the Factor Structure of the Emotion Regulation Checklist.

Emotion dysregulation (ED) is prevalent among youth with Attention-Deficit/Hyperactivity Disorder (ADHD) and significantly impacts functioning. Nuanced measurement of ED is central to understanding its role in this disorder and informing treatment approaches. The present study examined the factor structure of the Emotion Regulation Checklist (ERC) among children with ADHD with and without Oppositional Defiant Disorder (ODD). Exploratory factor analysis (EFA) conducted in a sample of 328 youth (mean age = 6.08) with ADHD indicated a four-factor solution, comprised of the following factors: Negative Emotion Lability, Positive Emotion Lability, Socially Appropriate Affect, and Socially Incongruent Affect. The Negative and Positive Emotion Lability subscales assess the reactivity of negatively and positively valenced emotions, respectively. The Socially Appropriate and Socially Incongruent Affect subscales provide an assessment of social-emotional functioning. All subscales discriminated between children with ADHD only and ADHD with co-morbid ODD, such that children with ODD had greater emotional lability and social-emotional difficulties. This revised factor structure of the ERC facilitates a uniquely brief, yet multifaceted and specific, assessment of emotional difficulties in children with ADHD that can inform treatment planning and operationalize emotional reactivity and social-emotional functioning in future research efforts.

Understanding Phasic Irritability: Anger and Distress in Children's Temper Outbursts.

Pediatric irritability can be highly impairing and is implicated in adverse outcomes. The phasic component, characterized by temper outbursts, is a frequent impetus to seek treatment. This study tested whether a previously described anger-distress model of tantrums applies to an outpatient sample of school-age children with clinically impairing temper outbursts (TO; 5.0-9.9 years; N = 86), and examined the clinical relevance of resulting factors through associations with measures of psychopathology, and differences between children with TO and two groups without: children with ADHD (n = 60) and healthy controls (n = 45). Factor analyses established a three-factor model: High Anger, Low Anger, Distress. These factors had unique associations with measures of irritability, externalizing problems, and internalizing problems in the TO group. Additionally, an interaction between groups and outburst factors emerged. Results provide evidence for the presence and clinical utility of the anger-distress model in children's outbursts and suggest avenues for future pediatric irritability research.

Editorial: A Call for Developmental Psychopathology Approaches to Diagnostic Nosology.

The publication of DSM-5 came with a number of significant advances, including shifts in disorder classifications and a new focus on dimensional assessment.1 It also introduced disruptive mood dysregulation disorder (DMDD), which was met with some criticism and concern. Although there was research to support the establishment of this new diagnosis aimed at improving classification of children and adolescents with persistent and impairing irritability,2 specific symptoms and definitions of frequency and impairment were not as empirically supported, and concerns arose regarding validity and reliability.3 The introduction of new diagnoses is a complex endeavor, particularly for disorders affecting children and adolescents, which require consideration of the immense neural, cognitive, and emotional changes occurring during this developmental period. Rigorous approaches grounded in developmental psychopathology are needed to establish a meaningful and clinically useful set of symptoms and associated characteristics. This is the approach that Wiggins et al.4 take to address the applicability of the DMDD diagnosis for children below the age of 6 years. Although this minimum age was included in DSM-5 to prevent unwarranted labeling of young children for whom temper outbursts are common,5 it fails to consider growing evidence of impairing irritability in preschoolers and limits identification of children who would benefit from early interventions. In response to this, these authors take a comprehensive bottom-up approach to empirically identify symptoms and to define limits of clinical severity, tailored specifically to preschool-aged children. As such, this study serves as a model of how to develop and to refine the diagnostic nosology of child psychiatric disorders.

A Preliminary Investigation of the Effects of a Western Diet on Hippocampal Volume in Children.

Introduction: Over the course of the 20th century, there has been a sharp increase in the consumption of saturated fat and refined sugars. This so-called "western diet" (WD) has been extensively linked to biological alterations and associated functional deficits in the hippocampus of animals. However, the effects of a WD on the human hippocampus are less well-characterized. This preliminary study aimed to extend prior animal work by investigating the effects of a WD on hippocampal volume in children. Methods: Twenty-one healthy children (ages 5-9) completed a structural T1-weighted magnetic resonance imaging scan. Bilateral hippocampal volumes (as regions-of-interest) and bilateral amygdala volumes (as medial temporal lobe control regions-of-interest) were calculated. WD variables were derived from the parent-completed Youth/Adolescent Food Frequency Questionnaire. Specifically, variables were calculated as percent of daily calories consumed from sugars, fats, or a combination of these (WD). Results: While the relationships between overall WD consumption and bilateral hippocampal volumes were not significant, increased fat consumption was significantly related to decreased left hippocampal volume. Sugar consumption was not related to hippocampal size. Control region volumes were not related to any diet variables. Discussion: This study is the first to directly link diet-specifically fat consumption-to decreased left hippocampal volume in children. This extends previous work showing smaller left hippocampal volume related to obesity in pediatric samples. Though preliminary, findings represent an important step toward understanding the impact of diet on child brain development.

Parental Responses to Temper Outbursts in Children With ADHD: The Role of Psychological Factors.

Objective: Children with ADHD frequently exhibit temper outbursts (TO). One related factor may be parental responses, such as harsh discipline and accommodation. This study tests the hypotheses that these responses will be associated with greater TO, and parental characteristics of higher anger and lower sense of competence, in children with ADHD. Method: Participants included 79 5- to 9-year-old children with ADHD (77.22% boys). Regressions were used to determine the association between parental psychological factors and responses to TO while covarying for TO frequency, severity, and duration. Results: Parental anger and sense of competence were not significantly related to any discipline responses after covarying for TO characteristics, although sense of competence predicted spanking at trend-level significance. Both parental anger and sense of competence significantly predicted accommodation over and above TO characteristics. Conclusion: Results underscore the importance of parental anger and sense of competency in predicting parental behavior, specifically parental accommodation.

Heterogeneity of the Anxiety-Related Attention Bias: A Review and Working Model for Future Research.

The anxiety-related attention bias (AB) has been studied for several decades as a clinically-relevant output of the dynamic and complex threat detection-response system. Despite research enthusiasm for the construct of AB, current theories and measurement approaches cannot adequately account for the growing body of mixed, contradictory, and null findings. Drawing on clinical, neuroscience, and animal models, we argue that the apparent complexity and contradictions in the empirical literature can be attributed to the field's failure to clearly conceptualize AB heterogeneity and the dearth of studies in AB that consider additional cognitive mechanisms in anxiety, particularly disruptions in threat-safety discrimination and cognitive control. We review existing research and propose a working model of AB heterogeneity positing that AB may be best conceptualized as multiple subtypes of dysregulated processing of and attention to threat anchored in individual differences in threat-safety discrimination and cognitive control. We review evidence for this working model and discuss how it can be used to advance knowledge of AB mechanisms and inform personalized prevention and intervention approaches.

The Contribution of Sensory Sensitivity to Emotional Lability in Children with ADHD Symptoms.

Emotional lability and sensory sensitivity have been shown to contribute to the overall clinical picture in children with attention deficit hyperactivity disorder (ADHD; Dunn & Bennett, 2002; Sobanski et al., 2010). Further, both of these characteristics have been individually demonstrated to contribute to poorer quality of life, increased functional impairment, and poorer treatment response (Anastopoulos et al., 2010; Boterberg & Warreyn, 2016). However, to date, no study has evaluated the relationship among all three of these factors. The current study hypothesized that increased sensory sensitivity would moderate the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in youth. Results indicate that heightened sensory sensitivity strengthens the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in children with three or more clinically impairing ADHD symptoms. This dimensional approach was taken in accordance with growing evidence that even children with sub-threshold ADHD experience significant functional impairment and high rates of sensory sensitivity (Hong et al., 2014). These findings suggest that clinicians treating children with ADHD symptoms and emotional lability should consider assessing for sensory sensitivity as integration of multi-sensory techniques or referral to concurrent occupational therapy may significantly improve treatment outcomes and quality of life for these children and their families.

Altered intrinsic functional connectivity of the cingulate cortex in children with severe temper outbursts.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

Disruptive Mood Dysregulation Disorder (DMDD): An RDoC perspective.

In recent years, there has been much debate regarding the most appropriate diagnostic classification of children exhibiting emotion dysregulation in the form of irritability and severe temper outbursts. Most recently, this has resulted in the addition of a new diagnosis, Disruptive Mood Dysregulation Disorder (DMDD) in the DSM 5. The impetus for including this new disorder was to reduce the number of diagnoses that these children would typically receive; however, there is concern that it has only complicated matters rather than simplifying them. For example, a recent epidemiologic study shows that DMDD cannot be differentiated from oppositional defiant disorder (ODD) based on symptoms alone. Thus, these children are an ideal population in which to apply RDoC constructs in order to obtain greater clarity in terms of underlying processes and ultimately, inform nosology and appropriate interventions. The aim of this article is to provide a foundation for future research by examining extant theoretical and empirical evidence for the role of four key RDoC constructs in DMDD.

Disruptive Mood Dysregulation Disorder: A New Diagnostic Approach to Chronic Irritability in Youth.

(Reprinted from the American Journal of Psychiatry 2014; 171:918-924 with permission from American Psychiatric Association Publishing).

Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography.

Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.

A Critical Review of Attentional Threat Bias and Its Role in the Treatment of Pediatric Anxiety Disorders.

Threat bias, or exaggerated selective attention to threat, is considered a key neurocognitive factor in the etiology and maintenance of pediatric anxiety disorders. However, upon closer examination of the literature, there is greater heterogeneity in threat-related attentional biases than typically acknowledged. This is likely impacting progress that can be made in terms of interventions focused on modifying this bias and reducing anxiety, namely attention bias modification training. We suggest that the field may need to "take a step back" from developing interventions and focus research efforts on improving the methodology of studying attention bias itself, particularly in a developmental context. We summarize a neurocognitive model that addresses the issue of heterogeneity by broadly incorporating biases toward and away from threat, linking this variation to key neurodevelopmental factors, and providing a basis for future research aimed at improving the utility of threat bias measures and interventions in clinical practice.

Alterations in amygdala functional connectivity reflect early temperament.

Behavioral inhibition (BI) is a temperament identified early in life that is associated with increased risk for anxiety disorders. Amygdala hyperresponsivity, found both in behaviorally inhibited and anxious individuals, suggests that amygdala dysfunction may represent a marker of anxiety risk. However, broader amygdala networks have not been examined in individuals with a history of childhood BI. This study uses resting state fMRI to assess amygdala intrinsic functional connectivity (iFC) in 38 healthy young adults (19 with a history of BI, 19 with no history of BI) selected from a longitudinal study. Centromedial, basolateral, and superficial amygdala iFCs were compared between groups and examined in relation to self-report measures of anxiety. Group differences were observed in amygdala iFC with prefrontal cortex, striatum, anterior insula, and cerebellum. Adults characterized with BI in childhood endorsed greater state anxiety prior to entering the scanner, which was associated with several of the group differences. Findings support enduring effects of BI on amygdala circuitry, even in the absence of current psychopathology.

Disruptive mood dysregulation disorder: a new diagnostic approach to chronic irritability in youth.

Disruptive mood dysregulation disorder (DMDD), a newcomer to psychiatric nosology, addresses the need for improved classification and treatment of children exhibiting chronic nonepisodic irritability and severe temper outbursts. In recent years, many of these children have been diagnosed with bipolar disorder, despite the lack of distinct mood episodes. This diagnostic practice has raised concerns, in part because of the escalating prescription of atypical antipsychotics. This article provides an overview of the limited literature on DMDD, including its history and relevant studies of assessment and treatment. A case study is included to illustrate key points, including diagnostic issues that clinicians may encounter when considering a diagnosis of DMDD.