Childhood Irritability Research Articles

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.

Changes in Early Childhood Irritability and Risk-Taking on the Cambridge Gambling Task (CGT) at 11 Years

Changes in Early Childhood Irritability and Risk-Taking on the Cambridge Gambling Task (CGT) at 11 Years

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

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. 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. 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. 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.

What I see, what you say: How cross-method variation sharpens characterization of irritability in early childhood.

Identification of clinically significant irritability in preschool age is important to implement effective interventions. However, varying informant and measurement methods display distinct patterns. These patterns are associated with concurrent and future mental health concerns. Patterns across multi-informant methods in early-childhood irritability may have clinical utility, identifying risk for impaired psychosocial functioning. Using data from the Multidimensional Assessment of Preschoolers Study (N=425), latent profile analysis identified irritability patterns through the parent-reported Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL), parent-reported interviewer-rated Preschool Age Psychiatric Assessment (PAPA), and observer-rated Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). These profiles were characterized on protective factors, global functioning, and mental health syndromes, concurrently and at early school age and preadolescent follow-up. Fit indices favored a five-class model: Low All, High Observation with Examiner (high DB-DOS Examiner Context), High All, High Parent Report (high MAPS-TL/PAPA), and Very High Parent Report (very high MAPS-TL/PAPA). Whereas Low All and High Observation with Examiner exhibited strong psychosocial functioning, remaining profiles showed impaired psychosocial functioning, with the Very High Parent Report group showing higher impairment at follow-ups, ds=0.37-1.25. Multi-informant measurements of irritability may have utility for clinical prediction, and future studies should test utility for diagnostic precision.

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

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. 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. 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). 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.

Autistic Children's Irritability During Social Communication Assessments.

Accurate measurement of autistic children's social communication is critical for assessing skills, setting intervention goals, evaluating change over time, determining service eligibility, and determining classroom placement. There are various types of assessments, some of which use specific tasks to elicit social communication. Structured tasks may frustrate children, inadvertently elicit irritability, and have a cascading effect on their ability to communicate. To date, no studies have evaluated how differing types of social communication assessments may exacerbate children's irritability and impact assessment scores. We examined the extent to which (a) social communication assessment type (structured vs. naturalistic) impacts autistic children's irritability and (b) child irritability is associated with social communication scores. Autistic toddlers (n = 114, Mage = 33.09 months, SD = 6.15) completed the Communication and Symbolic Behavior Scales (CSBS; structured) and a 10-min play-based mother-child interaction (MCX; naturalistic). Child irritability was scored on both assessments using a global rating scale of 0-15. Child irritability during the CSBS was significantly higher than during the MCX (V = 4892, p < .001, r = .68). Higher irritability was associated with lower CSBS social communication scores (B = -0.05, p = .03), but not MCX scores (B = 0.04, p = .13; Theil's F = 6.92, p = .009). Our findings suggest that the CSBS may pose unique challenges for autistic children, as it led to higher rates of irritability and negatively affected children's social communication scores. Evaluating the association between assessment type and irritability supports the complete characterization of autistic children's experience during assessments and clinicians in obtaining a more representative measure of social communication.

Aggression and Irritability in Middle Childhood: Between- and Within-Person Associations

ABSTRACT Objective This study tested predicted bidirectional associations between irritability and physical and relational forms of aggression, disentangling theorized within- and between-person effects using latent curve models with structured residuals (LCM-SR) over one year in middle childhood. Gender differences and robustness of results when controlling for other externalizing problems (i.e., attention problems, delinquency) were also considered. Method Children in third, fourth, and fifth grade (N = 704, 49.9% female) were recruited from schools in a large midwestern city. The sample was diverse in regard to race/ethnicity (31% Black, 29% White, 13% Hmong, 14% Latinx, 4% Native American, 4% Asian, 5% other races/ethnicities). Irritability, attention problems, and delinquency were measured using teacher-report, and physical and relational aggression were measured using self-report at three time points over one calendar year. Results At the between-person level, higher mean levels of irritability predicted higher initial levels of physical and relational aggression. Irritability continued to predict higher levels of physical aggression across the course of the study, whereas the effect of irritability on relational aggression diminished. Boys showed higher starting levels of physical aggression, but no other significant gender differences emerged. No significant within-person associations were found. Conclusions The present study suggests that irritability may represent a between-person risk factor for high levels of physical and relational aggression in middle childhood, although effects on physical aggression may be more persistent. This highlights the importance of considering affective processes to understand the development of aggression trajectories.

A cross-sectional analysis of the relationships between anxiety sensitivity and youth irritability: the mediated roles of insomnia and selective attention for threat

BackgroundIrritability is common in multiple psychiatric disorders and is hallmark of disruptive mood dysregulation disorder. Child irritability is associated with higher risk of suicide and adulthood mental health problems. However, the psychological mechanisms of irritability are understudied. This study examined the relationship between anxiety sensitivity and irritability among youth, and further explored three possible mediated factors: selective attention for threat, delayed reward discounting, and insomnia.MethodsParticipants were 1417 students (51.7% male; mean age 13.83 years, SD = 1.48) recruited from one high school in Hunan province, China. Self-report questionnaires were used to measure irritability (The Affective Reactivity Index and The Brief Irritability Test), anxiety sensitivity (The Childhood Anxiety Sensitivity Index), selective attention for threat (The Davos Assessment of Cognitive Biases Scale-attention for threat bias subscale), insomnia (The Youth Self-Rating Insomnia Scale), and delayed reward discounting (The 27-item Monetary Choice Questionnaire). Structural equation modal (SEM) was performed to examine mediated relations.ResultsAnxiety sensitivity was modestly related to irritability and insomnia (r from 0.25 to 0.54) and slightly correlated with selective attention for threat (r from 0.12 to 0.28). However, there is no significant relationship of delayed rewards discounting with anxiety sensitivity and irritability. The results of SEM showed that selective attention for threat (indirect effect estimate = 0.04) and insomnia (indirect effect estimate = 0.20) partially mediate the relationship between anxiety sensitivity and irritability, which explained 34% variation.ConclusionsAnxiety sensitivity is an important susceptibility factor for irritability. Selective attention for threat and insomnia are two mediated mechanisms to understand the relationship between anxiety sensitivity and irritability.

Prevalence, stability, and predictive utility of the Multidimensional Assessment of Preschoolers Scales clinically optimized irritability score: Pragmatic early assessment of mental disorder risk.

Characterizing the scope and import of early childhood irritability is essential for real-world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability. Data included two independent, diverse community samples of preschool age children (N=1857; N=1490), with a subset enriched for risk (N=425) assessed longitudinally from early childhood through preadolescence (∼4-9years old). A validated, brief (2-item) scale pragmatically assessed clinically significant irritability. In the longitudinal subsample, clinical interviews assessed internalizing/externalizing disorders. One in five preschool-age children had clinically significant irritability, which was independently replicated. Irritability was highly stable through preadolescence. Children with versus without clinically significant early childhood irritability had greater odds of early onset, persistent internalizing/externalizing disorders. The pragmatic assessment effectively screened out low-risk children and identified 2/3 of children with early-onset, persistent psychopathology. Clinically significant early childhood irritability prevalence is akin to the pediatric obesity epidemic and may warrant similar universal screening/intervention. Also, irritability's stability demonstrates the common guidance "they'll grow out of it" to be false. Finally, pragmatic irritability assessment has transdiagnostic predictive power and addresses a need for feasible measures to flag risk.

Parent–child relationships and early childhood irritability: A longitudinal moderated moderation model

The present study proposed a longitudinal moderated moderation model to investigate whether children's cognitive and emotional factors changed the association between parent-child relationships and early childhood irritability. A total of 526 parent-child pairs were included in a two–wave longitudinal study. We assessed children's emotion regulation skills, executive function, and relationships with parents at Wave 1 and irritability at Wave 2 one year later. The results revealed that high quality parent-child relationships were associated with lower levels of irritability. The two−way interaction effects of parent-child relationships × executive function, and emotion regulation skills ×executive function predicting irritability were significant. Moreover, the association between parent-child relationships and child irritability was moderated by emotion regulation skills and executive function simultaneously. Future interventions designed to reduce preschoolers' irritability may be more effective if they focus on improving parent-child relationships and promoting children's emotion regulation skills and executive function.

Associations between childhood irritability and neural reactivity to maternal feedback in adolescence

Early irritability, a transdiagnostic vulnerability for psychopathology, is associated with alterations in neural reactivity to emotional stimuli and reward; however, associations between childhood irritability and neural markers of risk may be mitigated by the quality of caregiving youth receive. We examined longitudinal relationships between irritability in childhood and young adolescents’ neural activity of regions typically associated with emotion regulation and reward processing during processing of maternal feedback and tested whether these associations were moderated by youth’s perceptions of the parent-child relationship quality. Eighty-one adolescents (Mage = 11.1 years) listened to maternal critical and praising feedback while undergoing functional magnetic resonance imaging. Age 3 irritability, assessed observationally, was negatively associated with age 11 neural reactivity to maternal criticism in a cluster in the right dorsolateral prefrontal cortex (dlPFC), particularly for youths who reported more positive maternal parenting. Given the role of the dlPFC activation in the effortful processing of emotional stimuli, decreased activation may reflect disengagement from negatively valenced interpersonal feedback in the context of a positive caregiving environment, thereby mitigating psychopathology risk associated with irritability.

Transactional associations of child irritability and anxiety with parent psychological control in Taiwanese school-aged children.

Child irritability and anxiety are associated with parent psychological control; yet their transactional relations over time are not well-characterized at the within-person level. Research addressing generalizability of past Western-based literature in non-Western, collectivist community samples is lacking. Sample comprised 285 children aged 8.8-11.4years (145 girls; Mage=9.9years, SD=0.6) in Northern Taiwan. Participants were assessed at baseline (T1), 6-month (T2), and 12-month (T3) follow-ups. Child irritability and anxiety symptoms were assessed using parent-rated Child Behavior Checklist. Parent psychological control was assessed using the parent- and child-rated Psychological Control Scale. Within-person processes were specified using the random-intercept cross-lagged panel models. Models showed that psychological control predicted increased child irritability when analyzing parenting data from parents and children. However, the lagged effect from psychological control to child anxiety was only seen in parent-rated parenting data. We found limited evidence for a back-and-forth transactional pathway among constructs. Child irritability predicted increased child anxiety in all models. Directional effects from psychological control to child irritability and anxiety support parent-involved interventions that prioritize collaborative parenting and positive reinforcement techniques. Future validations in combined clinical and typically developing samples and direct cross-cultural comparisons are warranted.

The role of parenting practices in parent and child mental health over time.

Parent and child mental health has suffered during the pandemic and transition phase. Structured and shared parenting may be intervention targets beneficial to families who are struggling with parent or child mental health challenges. First, we investigated associations between structured and shared parenting and parent depression symptoms. Second, we investigated associations between structured and shared parenting and depression, hyperactivity/inattention and irritability symptoms in children. A total of 1027 parents in two-parent households (4797 observations total; 85.1% mothers) completed online surveys about themselves and their children (aged 2-18 years) from April 2020 to July 2022. Structured parenting and shared parenting responsibilities were assessed from April 2020 to November 2021. Symptoms of parent depression, child depression, child hyperactivity and inattention, child irritability, and child emotional and conduct problems were assessed repeatedly (one to 14 times; median of four times) from April 2020 to July 2022. Parents who reported higher levels of shared parenting responsibilities had lower depression symptoms (β = -0.09 to -0.32, all P < 0.01) longitudinally. Parents who reported higher levels of shared parenting responsibilities had children with fewer emotional problems (ages 2-5 years; β = -0.07, P < 0.05), fewer conduct problems (ages 2-5 years; β = -0.09, P < 0.01) and less irritability (ages 13-18 years; β = -0.27, P < 0.001) longitudinally. Structured parenting was associated with fewer conduct problems (ages 2-5 years; β = -0.05, P < 0.05). Shared parenting is beneficial for parent and child mental health, even under chaotic or inflexible life conditions. Structured parenting is beneficial for younger children.

The Emotion Dysregulation Inventory−Young Child: Psychometric Properties and Item Response Theory Calibration in 2- to 5-Year-Olds

The Emotion Dysregulation Inventory (EDI) was designed and validated to quantify emotion dysregulation (ED) in children aged 6+ years. The purpose of this study was to adapt the EDI for use in young children (EDI-YC). Caregivers of 2,139 young children (aged 2-5 years) completed 48 candidate EDI-YC items. Factor and item response theory (IRT) analyses were conducted separately for clinical (neurodevelopmental disabilities; N= 1,369) and general population (N= 768) samples. The best-performing items across both samples were selected. Computerized adaptive testing simulations were used to develop a short-form version. Concurrent calibrations and convergent/criterion validity analyses were performed. The final calibrated item banks included 22 items: 15 items for Reactivity, characterized by rapidly escalating, intense, and labile negative affect, and difficulty down-regulating that affect; and 7 items for Dysphoria, characterized primarily by poor up-regulation of positive emotion, as well an item each on sadness and unease. The final items did not show differential item functioning based on age, sex, developmental status, or clinical status. IRT co-calibration of the EDI-YC Reactivity with psychometrically robust measures of anger/irritability and self-regulation demonstrated its superiority in assessing emotion dysregulation in as few as 7 items. EDI-YC validity was supported by expert review and its association with related constructs (eg, anxiety, depression, aggression, temper loss). The EDI-YC captures a broad range of emotion dysregulation severity with a high degree of precision in early childhood. It is suitable for use in all children aged 2 to 5 years, regardless of developmental concerns, and would be an ideal broadband screener for emotional/behavioral problems during well-child checks and to support early childhood irritability and emotion regulation research.

Changes in Early Childhood Irritability and Its Association With Depressive Symptoms and Self-Harm During Adolescence in a Nationally Representative United Kingdom Birth Cohort

This study aimed to investigate longitudinal associations between changes in early childhood irritability, and depressive symptoms and self-harm at 14 years. We used data from 7,225 children in a UK-based general population birth cohort. Childhood irritability was measured at 3, 5, and 7 years using 4 items from 2 questionnaires (the Children's Social Behaviour Questionnaire [CSBQ] and the Strengths and Difficulties Questionnaire [SDQ]). Participants reported depressive symptoms via the short Mood and Feelings Questionnaire (sMFQ) and self-harm via a single-item question, at 14 years. We used multilevel models to calculate within-child change in irritability between 3 and 7 years and examined associations between irritability, and depressive symptoms and self-harm at 14 years using linear and logistic regression models, respectively. We adjusted for child and family sociodemographic/economic characteristics, mental health difficulties, and child cognitive development. Irritability at ages 5 and 7 years was positively associated with depressive symptoms and self-harm at age 14 years. Irritability that remained high between 3 and 7 years was associated with depressive symptoms and self-harm at 14 years in unadjusted (depressive symptoms: β coefficient= 0.22, 95 % CI= 0.08-0.37, p= .003; self-harm: odds ratio= 1.09, 95 % CI= 1.01-1.16, p= .019) and adjusted models (depressive symptoms: β coefficient= 0.31, 95 % CI= 0.17-0.45, p< .001; self-harm: odds ratio= 1.12, 95 % CI= 1.0.4-1.19, p= .004). Results were similar in imputed samples. Children with irritability that remains high between 3 and 7 years are more likely to report higher depressive symptoms and self-harm during adolescence. These findings support early intervention for children with high irritability and universal interventions in managing irritability for parents of preschool-aged children.

Toward an optimized assessment of adolescent psychopathology risk: Multilevel environmental profiles and child irritability as predictors.

Adolescence is a developmental period during which youth experience vulnerability to psychopathology. To build the foundation for a parsimonious psychopathology risk calculator while capturing the complexity and dynamic nature of the environment, the current study aimed to identify distinct risk and resilience profiles with a wide range of environmental factors guided by Bronfenbrenner's biopsychosocial ecological system theory. The association between the early-mid childhood risk profiles and psychopathology in adolescence were examined. Moreover, the predictive utility of early childhood irritability was evaluated in addition to the risk profiles. The data from Future of Families and Child Wellbeing Study a nation-wide longitudinal study, were used in the latent profile analyses to identify the risk profiles with family, school, and neighborhood characteristics from 3 to 9years old. To capture the socio-environmental and cultural nuances, we extracted three subsamples, including Black/African American (n=2587), Hispanic/Latinx (n=1577), and White (n=776) for separate analyses. Risk profile memberships were used to predict adolescence psychopathology, including depression, anxiety, attention deficits, oppositional defiant disorder, and conduct disorder symptoms. The predictive utility of early childhood irritability above and beyond environmental risk profiles was evaluated using stepwise regression. Three risk profiles were identified in the Hispanic/Latinx and Black/African American subsamples, while four profiles were identified in White subsample. Almost all risk profile membership predicted both internalizing and externalizing psychopathology, while some profiles are predictive of externalizing symptoms only. Higher level of irritability predicted higher symptomatology in all five mental health outcomes above and beyond the environmental profiles. Distinct risk and resilience profiles primarily driven by parent and family characteristics were identified for all three major race/ethnicity groups. Our findings lay the foundation for a more efficient multi-tiered information gathering process in mental health clinical settings to aid the decision making for intervention and prevention.

Within-person pathways among maternal depressive symptoms and offspring internalizing problems from early childhood through adolescence.

The report examined reciprocal within-person associations among maternal depressive symptoms and offspring depressive, anxiety and irritability symptoms from early childhood to adolescence using a random intercept cross-lagged panel model (RI-CLPM). Participants were 609 mother-child dyads participating in the Stony Brook Temperament Study. Child and maternal internalizing symptoms were assessed every 3 years from ages 3 to 15 using maternal report on the Child Behavior Checklist (CBCL) and Diagnostic Inventory for Depression, respectively. At the between-person level, maternal depressive symptoms, and child depressive, anxiety, and irritability symptoms were all positively associated with one another. At the within-person level, greater within-person child anxiety symptoms at age 3 predicted both greater child anxiety and depressive symptoms at age 15 via greater child anxiety from ages 6 to 12, and greater within-person child irritability at age 3 predicted greater maternal depressive symptoms at age 15 via greater child irritability from ages 6 to 12. Findings reveal novel within-person developmental pathways from early childhood internalizing problems to later internalizing problems in both the child and mother. Intervention and prevention efforts should thus focus on early identification and prevention of childhood internalizing symptoms to reduce negative effects on both child and parent symptoms.

On the risks of secure attachment in infancy: Childhood irritability and adolescent depression predicted by secure attachment and high approach behaviours at 14-months towards a caregiver living with inter-parental violence

Introduction The secure infant turns to a caregiver for comfort when distressed or threatened. Does this level of openness create vulnerability where the caregiver is unsupportive or aggressive? In this study we examined prospectively whether secure attachment in infancy, and approach behaviours on reunion with a parent, were associated with childhood emotional dysregulation (irritability) and adolescent depression among children exposed to inter-parental violence. Methods We followed 219 families recruited from the general population during pregnancy (members of the Wirral Child Health and Development Study; WCHADS), with attachment assessments (Strange Situation Procedure; SSP) at 14 months, maternal interviews about inter-parental violence at 2.5, 5 and 7 years, and parent and teacher rated irritability at 9 years (CBCL). At age 13 years, 199 young people rated their levels of depression (SMFQ). In addition to the standard SSP classification, a latent variable reflecting approach behaviours during reunions was generated from the SSP dimensional scores and a factor score extracted. Analyses used path analysis using the gsem command in Stata. Results There were interactions between attachment security and inter-parental violence for age 9 irritability ( p = .084) and age 13 depression ( p = .039) which arose from greater levels of psychopathology among secure children exposed to inter-parental violence. Similarly, higher approach behaviours during SSP reunions among children exposed to inter-parental violence were associated with irritability (interaction term p = .004) and depression (interaction term p &amp;lt; .001). Among children who were not exposed to partner violence higher approach behaviours in the SSP were associated with lower irritability and depression. Conclusion Infant behaviours characteristic of attachment security in the Strange Situation Procedure may not equip children to deal with exposure to inter-parental violence and associated parental negativity.

Predictive Utility of Irritability “In Context”: Proof-of-Principle for an Early Childhood Mental Health Risk Calculator

ABSTRACT Objective We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes. Method Data were harmonized from two longitudinal early childhood subsamples (total N = 403; 50.1% Male; 66.7% Nonwhite; Mage = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (Mage = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model. Results Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39–66%. Conclusions Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity

BackgroundIrritability is a common symptom that may affect children’s brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4–8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. MethodsTypically developing children, ages 4–8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a “younger” cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an “older” cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. ResultsCross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. ConclusionsFindings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.