Frustrative Nonreward: Behavior, Circuits, Neurochemistry, and Disorders.

The surprising omission or reduction of vital resources (food, fluid, social partners) can induce an aversive emotion known as frustrative nonreward (FNR), which can influence subsequent behavior and physiology. FNR is an integral mediator of irritability/aggression, motivation (substance use disorders, depression), anxiety/fear/threat, learning/conditioning, and social behavior. Despite substantial progress in the study of FNR during the twentieth century, research lagged in the later part of the century and into the early twenty-first century until the National Institute of Mental Health's Research Domain Criteria initiative included FNR and loss as components of the negative valence domain. This led to a renaissance of new research and paradigms relevant to basic and clinical science alike. The COVID-19 pandemic's extensive individual and social restrictions were correlated with increased drug and alcohol use, social conflict, irritability, and suicide, all potential consequences of FNR. This article highlights animal models related to these psychiatric disorders and symptoms and presents recent advances in identifying the brain regions and neurotransmitters implicated.

The Irritable Infant in the Neonatal Intensive Care Unit: Risk Factors and Biomarkers of Gastroesophageal Reflux Disease.

OBJECTIVES: To determine risk factors for arching/irritability in high-risk infants and examine the significance of comorbidity and gastroesophageal reflux (GER) characteristics. STUDY DESIGN: Retrospective analysis of 24-hour pH-impedance studies of symptomatic infants in a neonatal intensive care unit (ICU) (n = 516, 30.1 ± 4.5 weeks of gestation, evaluated at 41.7 ± 3.2 weeks postmenstrual age) was conducted. Comparisons were made between infants with >72 vs ≤72 arching/irritability events per day. We characterized risk factors for arching/irritability along with clinical, pH-impedance, and outcome correlates. RESULTS: Of 39 973 arching/irritability events and 42 155 GER events, the averages per day were 77.6 ± 41.0 and 81.7 ± 48.2, respectively. Acid reflux and impedance bolus characteristics were not significantly different between infants with >72 and ≤72 arching/irritability events (P ≥ .05). The odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for postmenstrual age and weight at evaluation were significant for risk factors of preterm birth (2.3 [1.2-4.4]), moderate or severe neuropathology (2.0 [1.1-3.6]), and presence of oral feeding at testing (1.57 [1.07-2.30]). CONCLUSIONS: Acid GER disease is unlikely the primary cause of arching/irritability and empiric treatment should not be used when arching/irritability is present. Prematurity and neurologic impairment may be more likely the cause of the arching/irritability. Arching/irritability may not be a concern in orally fed infants.

Pathomechanisms of behavioral abnormalities in Huntington disease: an update.

Huntington disease (HD), a devastating autosomal-dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat, is clinically characterized by a triad of symptoms including involuntary motions, behavior problems and cognitive deficits. Behavioral symptoms with anxiety, irritability, obsessive-compulsive behaviors, apathy and other neuropsychiatric symptoms, occurring in over 50% of HD patients are important features of this disease and contribute to impairment of quality of life, but their pathophysiology is poorly understood. Behavior problems, more frequent than depression, can be manifest before obvious motor symptoms and occur across all HD stages, usually correlated with duration of illness. While specific neuropathological data are missing, the relations between gene expression and behavior have been elucidated in transgenic models of HD. Disruption of interneuronal communications, with involvement of prefronto-striato-thalamic networks and hippocampal dysfunctions produce deficits in multiple behavioral domains. These changes that have been confirmed by multistructural neuroimaging studies are due to a causal cascade linking molecular pathologies (glutamate-mediated excitotoxicity, mitochondrial dysfunctions inducing multiple biochemical and structural alterations) and deficits in multiple behavioral domains. The disruption of large-scale connectivities may explain the variability of behavior profiles and is useful in understanding the biological backgrounds of functional decline in HD. Such findings offer new avenues for targeted treatments in terms of minimizing neurobehavioral impairment in HD.

A network approach to the investigation of childhood irritability: probing frustration using social stimuli.

BACKGROUND: Self-regulation in early childhood develops within a social context. Variations in such development can be attributed to inter-individual behavioral differences, which can be captured both as facets of temperament and across a normal:abnormal dimensional spectrum. With increasing emphasis on irritability as a robust early-life transdiagnostic indicator of broad psychopathological risk, linkage to neural mechanisms is imperative. Currently, there is inconsistency in the identification of neural circuits that underlie irritability in children, especially in social contexts. This study aimed to address this gap by utilizing a functional magnetic resonance imaging (fMRI) paradigm to investigate pediatric anger/frustration using social stimuli. METHODS: Seventy-three children (M = 6 years, SD = 0.565) were recruited from a larger longitudinal study on irritability development. Caregivers completed questionnaires assessing irritable temperament and clinical symptoms of irritability. Children participated in a frustration task during fMRI scanning that was designed to induce frustration through loss of a desired prize to an animated character. Data were analyzed using both general linear modeling (GLM) and independent components analysis (ICA) and examined from the temperament and clinical perspectives. RESULTS: ICA results uncovered an overarching network structure above and beyond what was revealed by traditional GLM analyses. Results showed that greater temperamental irritability was associated with significantly diminished spatial extent of activation and low-frequency power in a network comprised of the posterior superior temporal sulcus (pSTS) and the precuneus (p < .05, FDR-corrected). However, greater severity along the spectrum of clinical expression of irritability was associated with significantly increased extent and intensity of spatial activation as well as low- and high-frequency neural signal power in the right caudate (p < .05, FDR-corrected). CONCLUSIONS: Our findings point to specific neural circuitry underlying pediatric irritability in the context of frustration using social stimuli. Results suggest that a deliberate focus on the construction of network-based neurodevelopmental profiles and social interaction along the normal:abnormal irritability spectrum is warranted to further identify comprehensive transdiagnostic substrates of the irritability.

Emotion regulation as central to psychopathology across childhood and adolescence: a commentary on Nobakht et al. (2023).

An important goal of clinical/developmental research is to identify factors contributing to the onset and maintenance of psychopathology - particularly factors that could be modified through intervention. Large-scale, multi-informant, longitudinal studies provide valuable opportunities for testing such etiological hypotheses, as illustrated by Nobakht et al.'s recent six-wave cohort study spanning ages 4-14. At a within-person level, emotion regulation (ER) deficits consistently predicted oppositional defiant disorder (ODD) symptoms (including both irritability and defiance), whereas victimization did not. These results comport with growing evidence highlighting ER's centrality to ODD and psychopathology more broadly. While the ER findings carry promising implications, caution is warranted in interpreting the results for victimization given that its association with psychopathology is well-documented. More research is needed to test precise questions about within- and between-person processes involving ER, victimization, and psychopathology across development. Pressing research questions include whether, how, and when youths' ER can be modified, and with what effects on clinical outcomes.

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.

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.

Social anxiety moderates the association between adolescent irritability and bully perpetration.

BACKGROUND: Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors. METHODS: A sample of adolescents (n = 169, mean = 12.42 years of age) were assessed using clinician rated assessments of anxiety, parent reports of irritability and bullying behaviors (perpetration, generalized aggression, and victimization). Correlations assessed zero-order relations between variables, and regression-based moderation analyses were used to test interactions. Johnson-Neyman methods were used to represent significant interactions. RESULTS: Irritability was significantly related to bullying (r = .403, p < .001). Social, but not generalized, anxiety symptoms significantly moderated the effect of irritability on bully perpetration (t(160) = -2.94, b = -.01, p = .0038, ΔR2 = .0229, F(1, 160) = 8.635). As social anxiety symptoms increase, the link between irritability and perpetration decreases. CONCLUSIONS: Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. Comprehensively assessing how treatment of psychopathology impacts social behaviors may improve future intervention.

Irritability: associations with real-time affect dynamics, social interactions, and daily substance use in older adolescents.

Irritability is a common and clinically significant symptom associated with a wide range of negative outcomes. Ecological Momentary Assessment (EMA) is a valuable tool for capturing experiences, such as emotions, social interactions, and substance use in real-time, and may be useful in understanding how irritability is related to everyday functioning. We investigated cross-sectional associations between a widely used self-report irritability rating scale and affect dynamics, social interactions, and substance use captured with EMA (5 surveys daily for 14 days) in 349 18-year-olds. We also examined the associations of self- and parent-reported irritability at ages 12 and 15 with the age 18 EMA variables to explore whether these relationships persist over time. Youth-reported irritability at age 18 was linked to greater intensity, variability, and inertia of irritability, sadness, and anxiety, less positive and more negative interpersonal experiences, and greater cigarette and drug use. Most effect sizes were in the medium-small range. Associations of youth- and parent-reported irritability at ages 12 and 15 with the age 18 EMA measures were generally similar, although smaller in magnitude. Findings contribute to understanding how irritability is manifested in real-time affect dynamics and interpersonal functioning, as well as daily substance use. Most effects were evident over the course of up to 6 years - that is, early adolescent irritability, reported by both youth and their parents, was associated with similar real-time affect dynamics and interpersonal experiences at age 18. This study contributes to the literature on the developmental psychopathology of irritability by extending findings to everyday functioning.

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.

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.

A systematic review of the psychometric properties of tools for measuring depression in youths with intellectual disability.

While youths with intellectual disability (ID) have increased vulnerability for depressive disorders, cognitive problems and combined functional barriers make them less prone to receive adequate treatments. A systematic review of the literature was conducted (PROSPERO Registration number: CRD42022347703) based on several databases from 1980 to 2022 to examine the quality of tools for measuring depression in children and adolescents with ID. The COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) checklist was used to assess several psychometric domains. Twelve studies evaluated the properties of six tools for measuring depression in youths with ID. The Center for Epidemiologic Studies Depression Scale-Intellectual Disability (CESD-ID) was the only scale with at least five domains of psychometric properties assessed to have strong or moderate evidence. Based on the reviewed findings, tools specifically developed for populations with developmental disabilities should be considered first in order to screen depression in youths with ID. Much work is required to confirm their validity in clinical samples with patients with a complex form of developmental disabilities. As a complement to self- and caregivers-report questionnaires, clinician rating scales were considered useful to catch the full picture of depression in youths with ID, in particular associated behavioral expressions. Their validity received little scrutiny and certainly deserve more attention to improve care practice of youths with ID.

Understanding irritability through the lens of self-regulatory control processes in children and adolescents: a systematic review.

Among youths, pathological irritability is highly prevalent and severely disabling. As a frequent symptom, it often leads to referrals to child and adolescent mental health services. Self-regulatory control (SRC) processes are a set of socio-psycho-physiological processes that allow individuals to adapt to their ever-changing environments. This conceptual framework may enhance the current understanding of the cognitive, emotional, behavioural and social dysregulations underlying irritability. The present systematic review (PROSPERO registration: #CRD42022370390) aims to synthesize existing studies that examine irritability through the lens of SRC processes among youths (< 18 years of age). We conducted a comprehensive literature search among six bibliographic databases: Embase.com, Medline ALL Ovid, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley and ProQuest Dissertations & Theses A&I. Additional searches were performed using citation tracing strategies. The retrieved reports totalled 2612, of which we included 82 (i.e., articles) from 74 studies. More than 85% of reports were published during the last 6 years, highlighting the topicality of this work. The studies sampled n = 26,764 participants (n = 12,384 girls and n = 12,905 boys, n = 1475 no information) with an average age of 8.08 years (SD = 5.26). The included reports suggest that irritability has an association with lower effortful control, lower cognitive control and delay intolerance. Further, evidence indicates both cross-sectional and longitudinal associations between irritability and a lack of regulation skills for positive and negative emotions, particularly anger. Physiological regulation seems to moderate the association between irritability and psychopathology. Finally, the mutual influence between a child's irritability and parenting practice has been established in several studies. This review uses the lens of SRC to illustrate the current understanding of irritability in psychopathology, discusses important gaps in the literature, and highlights new avenues for further research.

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.

Dysfunction in differential reward-punishment responsiveness in conduct disorder relates to severity of callous-unemotional traits but not irritability.

BACKGROUND: Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD. METHODS: The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment. RESULTS: Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices. CONCLUSIONS: The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Categorical and dimensional approaches to the developmental relationship between ADHD and irritability.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and irritability commonly co-occur, and follow similar developmental trajectories from childhood to adolescence. Understanding of the developmental relationship between these co-occurrences is limited. This study provides a longitudinal assessment of how ADHD diagnostic status and symptom patterns predict change in irritability. METHODS: A community sample of 337 participants (45.2% ADHD), recruited for the Childhood Attention Project, completed the Affective Reactivity Index (ARI) to measure irritability at baseline (mean age 10.5 years) and follow-up after 18-months. Latent change score models were used to assess how (a) baseline ADHD vs. control group status, (b) baseline symptom domain (inattention, hyperactivity-impulsivity) and (c) longitudinal change in ADHD symptom severity predicted change in irritability. RESULTS: Irritability was significantly higher among the ADHD group than controls; however, change in irritability over time did not differ between groups. When assessed across the entire cohort, change in irritability was predicted by higher symptom count in the hyperactive-impulsive domain, but not the inattentive domain. Greater declines in ADHD symptoms over time significantly predicted greater declines in irritability. Baseline ADHD symptom severity was found to significantly predict change in irritability; however, baseline irritability did not significantly predict change in ADHD symptoms. CONCLUSIONS: ADHD symptoms-particularly hyperactive-impulsive symptoms-predict the degree and trajectory of irritability during childhood and adolescence, even when symptoms are below diagnostic thresholds. The use of longitudinal, dimensional and symptom domain-specific measures provides additional insight into this relationship.

Tonic and phasic irritability in 6-year-old children: differential correlates and outcomes.

OBJECTIVE: Irritability is a common and clinically important problem in children and adolescents and a risk factor for later psychopathology and impairment. Irritability can manifest in both tonic (e.g., irritable, touchy mood) and phasic (e.g., temper outburst) forms, and recent studies of adolescents suggest that they predict different outcomes. However, no studies have examined whether tonic and phasic irritability are empirically distinguishable in 6-year-old children and whether they have distinct correlates and outcomes. METHOD: We utilized data from a longitudinal study of an unselected community sample of four hundred fifty-two 6-year-olds followed at 3-year intervals to age 15. We conducted confirmatory factor analysis (CFA) using relevant items from a diagnostic interview and several parent-report inventories. RESULTS: The CFA identified dimensions that were consistent with tonic and phasic irritability. Tonic irritability was independently associated with concurrent parent-reported temperamental negative affectivity and internalizing and externalizing disorders at age 6 and predicted higher rates of internalizing psychopathology, and suicidal ideation, in adolescence. Phasic irritability was independently associated with concurrent parent-reported temperamental negative affectivity, surgency, and low effortful control, maladaptive parenting styles and practices, and externalizing disorders at age 6, and predicted higher rates of externalizing psychopathology in adolescence. CONCLUSIONS: Tonic and phasic irritability in 6-year-old children appear to be distinguishable constructs with different temperament and parenting correlates and psychopathological outcomes. Distinguishing these components has implications for research on the etiology and pathophysiology of irritability and developing effective treatments.

Irritability and rejection-elicited aggression in adolescents and young adults.

BACKGROUND: Violence exacts staggering personal and financial costs - a burden disproportionally born by adolescents and young adults. This may be partially due to an increased sensitivity to social rejection during this critical phase of development. Irritability, a transdiagnostic symptom, is often elicited by social interactions. Yet, little is known about age differences in social rejection-elicited aggression and irritability. Progress toward testing such relations has been hindered by a lack of ecologically-valid tasks that enable the measurement of in-the-moment social rejection-elicited aggression. METHODS: In this paper, we describe an initial study of young adults (n = 55) that demonstrates the efficacy of a novel Virtual School and Aggression Paradigm (VS-AP). Next, we replicate these results in a second study of adolescents and young adults (ages 11-25 years; n = 173) and examine relations between social rejection-elicited aggression, irritability, and age. RESULTS: We found that aggressive behavior in the VS-AP differed for accepting, rejecting, and unpredictable peer types (Study 1: F(2, 108) = 20.57, p < .001, ε2 = .28; Study 2: F(2, 344) = 152.13, p < .001, ε2 = .47), demonstrating that the VS-AP successfully models social rejection-elicited aggression. In Study 2, age was negatively correlated with aggressive behavior (r = -.29, p < .001) and irritability (r = -.28, p < .001), while irritability was positively correlated with aggressive behavior (r = .28, p < .001). Age moderated the relation between social rejection-elicited aggression and irritability. Specifically, irritability was more predictive of aggression in young adults than in adolescents (F(3, 167) = 7.07, p < .001). CONCLUSIONS: Data suggest mechanisms promoting rejection-elicited aggression may differ across development and vary for those with and without high levels of irritability. The VS-AP is a promising tool for probing neurocognitive, developmental, and clinically relevant mechanisms underlying social rejection-elicited aggression.

Peer functioning difficulties may exacerbate symptoms of attention-deficit/hyperactivity disorder and irritability over time: a temporal network analysis.

BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) have been consistently found to experience impairments in peer functioning. Irritability is highly prevalent in children with ADHD and may worsen social impairments given the frequent temper outbursts and low frustration tolerance characterizing irritability. However, it is still unclear how ADHD and irritability symptoms interact with peer functioning difficulties over time. Assessing these temporal dynamics using a novel longitudinal approach (i.e., temporal network analysis) may reveal precise targets for intervention. METHODS: This study investigates the dynamic associations between ADHD symptoms, irritability, and peer functioning in a community sample of 739 children (ages 8-11 years, Mage = 10.06 [SD = 0.59], 47.77% females) assessed at three timepoints, 6 months apart, in a school-based study. Parents reported their child's ADHD symptoms using the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV), and irritability symptoms using the Child Behavior Checklist (CBCL) irritability items. Children's peer functioning (i.e., peer acceptance, peer rejection, number of friendships, and victimization) was measured via peer nomination. To estimate the longitudinal associations between the variables, we built a graphical vector autoregression model for panel data. RESULTS: The longitudinal network highlighted that poor peer functioning contributed to increases in symptoms over time. Specifically, (1) physical victimization predicted increases in inattention, hyperactivity, and irritability; (2) peer rejection predicted increases in inattention, which in turn predicted increases in irritability; (3) peer acceptance predicted decreases in inattention and irritability; and (4) higher numbers of mutual friendships increased inattention. CONCLUSIONS: These results suggest that a negative social environment involving physical bullying and rejection may aggravate ADHD and irritability symptoms. Conversely, positive social interactions, such as being liked by peers, may improve inattention and irritability symptoms. Fostering social-emotional skills and positive social interactions and environments in children with ADHD and irritability may be a promising target for future interventions to reduce symptoms.

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.