Task-Rest Reconfiguration Efficiency of the Reward Network Across Adolescence and Its Association With Early Life Stress and Depressive Symptoms.

OBJECTIVE: Adolescents face significant changes in many domains of their daily lives that require them to flexibly adapt to changing environmental demands. To shift efficiently among various goals, adolescents must reconfigure their brains, disengaging from previous tasks and engaging in new activities. METHOD: To examine this reconfiguration, we obtained resting-state and task-based functional magnetic resonance imaging (fMRI) scans in a community sample of 164 youths. We assessed the similarity of functional connectivity (FC) of the reward network between resting state and a reward-processing state, indexing the degree of reward network reconfiguration required to meet task demands. Given research documenting relations among reward network function, early life stress (ELS), and adolescent depression, we examined the association of reconfiguration efficiency with age across adolescence, the moderating effect of ELS on this association, and the relation between reconfiguration efficiency and depressive symptoms. RESULTS: We found that older adolescents showed greater reconfiguration efficiency than younger adolescents and, furthermore, that this age-related association was moderated by the experience of ELS. CONCLUSION: These findings suggest that reconfiguration efficiency of the reward network increases over adolescence, a developmental pattern that is attenuated in adolescents exposed to severe ELS. In addition, even after controlling for the effects of age and exposure to ELS, adolescents with higher levels of depressive symptoms exhibited greater reconfiguration efficiency, suggesting that they have brain states at rest that are more strongly optimized for reward processing than do asymptomatic youth. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

Differentiating neural sensitivity and bias during face-emotion processing in youth: a computational approach.

The ability to interpret face-emotion displays is critical for the development of adaptive social interactions. Using a novel variant of a computational model and fMRI data, we examined behavioral and neural associations between two metrics of face-emotion labeling (sensitivity and bias) and age in youth. Youth and adults (n = 44, M age = 20.02, s.d. = 7.44, range = 8-36) completed an explicit face-emotion labeling fMRI task including happy to angry morphed face emotions. A drift-diffusion model was applied to choice and reaction time distributions to examine sensitivity and bias in interpreting face emotions. Model fit and reliability of parameters were assessed on adult data (n = 42). Linear and quadratic slopes modeled brain activity associated with dimensions of face-emotion valence and ambiguity during interpretation. Behaviorally, age was associated with sensitivity. The bilateral anterior insula exhibited a more pronounced neural response to ambiguity with older age. Associations between sensitivity and bias metrics and activation patterns indicated that systems encoding face-emotion valence and ambiguity both contribute to the ability to discriminate face emotions. The current study provides evidence for age-related improvement in perceptual sensitivity to facial affect across adolescence and young adulthood.

Associations Between Neighborhood Resources and Youths' Response to Reward Omission in a Task Modeling Negatively Biased Environments.

OBJECTIVE: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards. METHOD: To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology. RESULTS: Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R2 = 0.42) and more sadness (p < .001, marginal R2 = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R2 = 0.076), reduced connectivity between the somatic-motor-salience and the control network (p = .041, marginal R2 = 0.040), and fewer provincial hubs in the somatic-motor-salience, control, and default mode networks (all pFWE < .05). CONCLUSION: The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. 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. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

Irritability, Negative Life Events and the Course of Anxiety and Depressive Symptoms in a Clinical Sample of Youth: A Longitudinal Study.

Objective: Irritability, the tendency to react with anger, and the experience of negative life events (NLE) have independently been associated with the emergence of anxiety and depression. Here, we investigate how irritability and cumulative effects of NLE interactively predict the course of anxiety and depression in the context of common psychiatric disorders. Method: 432 youth with no psychiatric diagnosis, or a diagnosis of an anxiety disorder, Attention-Deficit/ Hyperactivity Disorder (ADHD), or Disruptive Mood Dysregulation Disorder (DMDD), participated in this study. At baseline, we assessed NLE, parent and youth reports of irritability and anxiety, and youth reports of depression. Symptoms were annually reassessed for up to four years. Results: In youth without psychiatric diagnoses but with elevated baseline irritability, the presence of NLE predicted decreasing anxiety, while the absence of NLE predicted increasing anxiety. In youth with an anxiety disorder, elevated baseline irritability predicted decreasing anxiety independent of NLE, while a large cumulative effect of NLE predicted increasing depression. NLE predicted persisting mild anxiety in ADHD and persisting mild depressive symptoms in DMDD. Conclusion: Our findings suggest that, particularly in non-referred samples, NLE might moderate the relationship between irritability and future anxiety such that irritability/ anger in the context of NLE can positively affect the course of anxiety. Future work replicating this finding while repeatedly measuring NLE and rigorously controlling for potentially confounding effects of treatment, is warranted.

Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations.

OBJECTIVE: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure. METHOD: We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA). RESULTS: The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρS = 0.88, pFDR < .001) and negatively related to whole-brain FA (r = -0.20), as well as FA of the corticospinal tract (all pFWE < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = -0.16, pFWE < .05). Inattention-specific and irritability-specific factors were not linked to FA. CONCLUSION: Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation.

Multivariate Assessment of Inhibitory Control in Youth: Links With Psychopathology and Brain Function.

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8-18 years old) with varying symptom types and levels. Participants were recruited from the Washington, D.C., metro region. Results of structural equation modeling integrating a bifactor model of psychopathology revealed that inhibitory control predicted a shared or general psychopathology dimension, but not ADHD-specific, anxiety-specific, or irritability-specific dimensions. Inhibitory control also showed a significant, selective association with global efficiency in a frontoparietal control network delineated during resting-state functional magnetic resonance imaging. These results support performance-based inhibitory control linked to resting-state brain function as an important predictor of comorbidity in youth psychopathology.

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.

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.

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

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

Evaluating the development and well-being assessment (DAWBA) in pediatric anxiety and depression.

Enhancing screening practices and developing scalable diagnostic tools are imperative in response to the increasing prevalence of youth mental health challenges. Structured lay psychiatric interviews have emerged as one such promising tool. However, there remains limited research evaluating structured psychiatric interviews, specifically their characterization of internalizing disorders in treatment-seeking youth. This study evaluates the relationship between the Development and Well-Being Assessment (DAWBA), a structured psychiatric interview, and established measures of pediatric anxiety and depression, including the Screen for Child Anxiety Related Disorders (SCARED), the Pediatric Anxiety Rating Scale (PARS), and the Mood and Feelings Questionnaire (MFQ). The study comprised two independent clinical samples of treatment-seeking youth: sample one included 55 youth with anxiety and 29 healthy volunteers (HV), while sample two included 127 youth with Major Depressive Disorder and 73 HVs. We examined the association between the DAWBA band scores, indicating predicted risk for diagnosis, the SCARED and PARS (sample one), and the MFQ (sample two). An exploratory analysis was conducted in a subset of participants to test whether DAWBA band scores predicted the change in anxiety symptoms (SCARED, PARS) across a 12-week course of cognitive behavioral therapy. The results revealed that the DAWBA significantly predicted the SCARED, PARS and MFQ measures at baseline; however, it did not predict changes in anxiety symptoms across treatment. These findings suggest that the DAWBA may be a helpful screening tool for indexing anxiety and depression in treatment-seeking youth but is not especially predictive of longitudinal trajectories in symptomatology across psychotherapy.

Selecting an Ecological Momentary Assessment Platform: Tutorial for Researchers.

BACKGROUND: Although ecological momentary assessment (EMA) has been applied in psychological research for decades, delivery methods have evolved with the proliferation of digital technology. Technological advances have engendered opportunities for enhanced accessibility, convenience, measurement precision, and integration with wearable sensors. Notwithstanding, researchers must navigate novel complexities in EMA research design and implementation. OBJECTIVE: In this paper, we aimed to provide guidance on platform selection for clinical scientists launching EMA studies. METHODS: Our team includes diverse specialties in child and adolescent behavioral and mental health with varying expertise on EMA platforms (eg, users and developers). We (2 research sites) evaluated EMA platforms with the goal of identifying the platform or platforms with the best fit for our research. We created a list of extant EMA platforms; conducted a web-based review; considered institutional security, privacy, and data management requirements; met with developers; and evaluated each of the candidate EMA platforms for 1 week. RESULTS: We selected 2 different EMA platforms, rather than a single platform, for use at our 2 research sites. Our results underscore the importance of platform selection driven by individualized and prioritized laboratory needs; there is no single, ideal platform for EMA researchers. In addition, our project generated 11 considerations for researchers in selecting an EMA platform: (1) location; (2) developer involvement; (3) sample characteristics; (4) onboarding; (5) survey design features; (6) sampling scheme and scheduling; (7) viewing results; (8) dashboards; (9) security, privacy, and data management; (10) pricing and cost structure; and (11) future directions. Furthermore, our project yielded a suggested timeline for the EMA platform selection process. CONCLUSIONS: This study will guide scientists initiating studies using EMA, an in vivo, real-time research tool with tremendous promise for facilitating advances in psychological assessment and intervention.

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

OBJECTIVE: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT. METHODS: Unmedicated youths diagnosed with an anxiety disorder underwent 12 weeks of CBT as part of two randomized clinical trials testing the efficacy of adjunctive computerized cognitive training. Across both trials, participants completed a threat-processing task during functional MRI before and after treatment. Age-matched healthy comparison youths completed two scans over the same time span. The mean age of the samples was 13.20 years (SD=2.68); 41% were male (youths with anxiety disorders, N=69; healthy comparison youths, N=62). An additional sample including youths at temperamental risk for anxiety (N=87; mean age, 10.51 years [SD=0.43]; 41% male) was utilized to test the stability of anxiety-related neural differences in the absence of treatment. Whole-brain regional activation changes (thresholded at p<0.001) were examined using task-based blood-oxygen-level-dependent response. RESULTS: Before treatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy comparison children across all task conditions. Fronto-parietal hyperactivation normalized over the course of treatment, whereas limbic responses remained elevated after treatment. In the at-risk sample, overlapping clusters emerged between regions showing stable associations with anxiety over time and regions showing treatment-related changes. CONCLUSIONS: Activation in fronto-parietal networks may normalize after CBT in unmedicated pediatric anxiety patients. Limbic regions may be less amenable to acute CBT effects. Findings from the at-risk sample suggest that treatment-related changes may not be attributed solely to the passage of time.

Editorial: Baby Steps on Challenging Ground: Understanding How Early-Life Irritability Impacts Mental Health Outcomes.

Irritability is increasingly recognized as an important phenotype in early life. Since the groundbreaking longitudinal work in infants with difficult temperament by Chess and Thomas,1 conceptualizations of early irritability have grown and matured in the literature. Today, multiple measures of early irritability are available with a focus on dispositional anger, frustration, and negative reactivity. Additionally, investigators have mapped the normative developmental trajectory of irritability, which features a peak in temper tantrums in early childhood.2 This latter phenomenon creates an interesting challenge for research interrogating the clinical relevance of early irritability for later mental health in youth. How do we ascertain what is clinically meaningful in early life against the backdrop of wide individual and developmental variation in irritability?

Ecological Momentary Assessment of Youth Anxiety: Evaluation of Psychometrics for Use in Clinical Trials.

Background: Ecological momentary assessment (EMA) captures naturalistic experience in real time and holds promise to improve our understanding and treatment of youth psychopathology. While psychometric evaluation of EMA methods is crucial, particularly for use as a tool in clinical trials, research examining the reliability and validity of EMA items in youth is lacking. Method: This study evaluates EMA responses from 204 child and adolescent participants (M age = 12.54, 60.8% female), including 131 participants with an anxiety disorder and 73 participants with no psychiatric diagnosis. We assessed the within- and between-person variability, internal consistency, test-retest reliability, and convergent and discriminant validity of two EMA items probing anxiety symptoms; one positive affect item served as a comparison. Results: All psychometric properties of the anxiety items were at least satisfactory in youth with anxiety disorders. However, there was restricted variability and poor test-retest reliability in youth with no diagnosis. Discussion: These results might facilitate future clinical trials using EMA to investigate pediatric anxiety. Results also suggest that unique EMA items might be needed to reliably track anxiety in healthy youth. Future work should continue to examine the psychometric properties of EMA protocols before implementation in clinical trials. ClinicalTrials.gov identifier: NCT00018057.

An Exposure-Based Cognitive-Behavioral Therapy for Youth with Severe Irritability: Feasibility and Preliminary Efficacy.

OBJECTIVE: Clinically impairing irritability and temper outbursts are among the most common psychiatric problems in youth and present transdiagnostically; however, few mechanistically informed treatments have been developed. Here, we test the acceptability, feasibility, and preliminary efficacy of a novel exposure-based treatment with integrated parent management skills for youth with severe irritability using a randomized between-subjects multiple baseline design. METHOD: N = 41 patients (Age, Mean (SD) = 11.23 years (1.85), 62.5% male, 77.5% white) characterized by severe and impairing temper outbursts and irritability were randomized to different baseline observation durations (2, 4, or 6 weeks) prior to active treatment; 40 participants completed the 12 session treatment of exposure-based cognitive-behavioral therapy for irritability with integrated parent management skills. Masked clinician ratings were acquired throughout baseline and treatment phases, as well as 3- and 6-months post-treatment. To examine acceptability and feasibility, drop-out rates and adverse events were examined. Primary clinical outcome measures included clinician-administered measures of irritability severity and improvement. Secondary clinical outcome measures included multi-informant measures of irritability, depression, anxiety, and attention-deficit/hyperactivity disorder symptoms. RESULTS: No patients dropped out once treatment began, and no adverse events were reported. Irritability symptoms improved during the active phase of treatment across all measurements (all ßs > -0.04, ps < .011, Cohen's d range: -0.33 to -0.98). Treatment gains were maintained at follow-up (all ßs(39) < -0.001, ps > .400). Sixty-five percent of patients were considered significantly improved or recovered post-treatment based on the primary clinician-rated outcome measure. CONCLUSIONS: Results support acceptability, feasibility, and preliminary efficacy of this novel treatment for youth with severe irritability. Limitations and future directions are also discussed.

Robust caregiver-youth discrepancies in irritability ratings on the affective reactivity index: An investigation of its origins.

OBJECTIVE: The Affective Reactivity Index (ARI) is widely used to assess young people's irritability symptoms, but youth and caregivers often diverge in their assessments. Such informant discrepancy might be rooted in poor psychometric properties, the differential conceptualization of irritability across informants, or reflect sociodemographic and clinical characteristics. We use an out-of-sample replication approach and leverage longitudinal data, available for a subset of the participants, to test these hypotheses. METHOD: Across two independent samples (NCohort-1 = 765, 8-21 years; NCohort-2 = 1910, 6-21 years), we investigate the reliability and measurement invariance of the ARI, examine sociodemographic and clinical predictors of discrepant reporting and probe the utility of a bifactor model for cross-informant integration. RESULTS: Despite good internal consistency and 6-week-retest-reliability of parent (Cohort-1: α = 0.92, ICC = 0.85; Cohort-2: α = 0.93) and youth forms (Cohort-1: α = 0.88, ICC = 0.78; Cohort-2: α = 0.82), we confirm substantial informant discrepancy in ARI ratings (3 points on a scale from 0 to 12), which is stable over six weeks (ICC = 0.53). Measurement invariance across informants was weak, indicating that parents and youth may interpret ARI items differently. Irritability severity and diagnostic status predicted informant-discrepancy, albeit in opposing directions: higher severity was linked to relative, higher irritability-ratings by youth (Cohort-1: ß = -0.06, p < .001; Cohort-2: ß = -0.06, p < .001), while diagnoses of Disruptive Mood Dysregulation Disorder (Cohort-1: ß = 0.44, p < .001; Cohort-2: ß = 0.84, p < .001) and Oppositional Defiant Disorder (Cohort-1: ß = 0.41, p < .001; Cohort-2: ß = 0.42, p < .001) predicted relative higher irritability-ratings by caregivers. In both datasets, a bifactor model parsing informant-specific from shared irritability-related variance fit the data well (CFI = 0.99, RMSEA = 0.05; N2: CFI = 0.99; RMSEA = 0.04). CONCLUSION: Parent and youth ARI reports and their discrepancy are reliable and reflect different interpretations of the scale items; hence they should not be averaged. This finding also suggests that irritability is not a unitary construct. Future work should investigate and model how different aspects of irritability might differ in their impact on the responses of specific informants.

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.

Parenting and childhood irritability: Negative emotion socialization and parental control moderate the development of irritability.

Irritability, characterized by anger in response to frustration, is normative in childhood. While children typically show a decline in irritability from toddlerhood to school age, elevated irritability throughout childhood may predict later psychopathology. The current study (n = 78) examined associations between trajectories of irritability in early childhood (ages 2-7) and irritability in adolescence (age 12) and tested whether these associations are moderated by parenting behaviors. Results indicate that negative emotion socialization moderated trajectories of irritability - relative to children with low stable irritability, children who exhibited high stable irritability in early childhood and who had parents that exhibited greater negative emotion socialization behaviors had higher irritability in adolescence. Further, negative parental control behavior moderated trajectories of irritability - relative to children with low stable irritability, children who had high decreasing irritability in early childhood and who had parents who exhibited greater negative control behaviors had higher irritability in adolescence. In contrast, positive emotion socialization and control behaviors did not moderate the relations between early childhood irritability and later irritability in adolescence. These results suggest that both irritability in early childhood and negative parenting behaviors may jointly influence irritability in adolescence. The current study underscores the significance of negative parenting behaviors and could inform treatment.

Cross-sectional and Longitudinal Associations of Anxiety and Irritability With Adolescents' Neural Responses to Cognitive Conflict.

BACKGROUND: Psychiatric symptoms are commonly comorbid in childhood. The ability to disentangle unique and shared correlates of comorbid symptoms facilitates personalized medicine. Cognitive control is implicated broadly in psychopathology, including in pediatric disorders characterized by anxiety and irritability. To disentangle cognitive control correlates of anxiety versus irritability, the current study leveraged both cross-sectional and longitudinal data from early childhood into adolescence. METHODS: For this study, 89 participants were recruited from a large longitudinal research study on early-life temperament to investigate associations of developmental trajectories of anxiety and irritability symptoms (from ages 2 to 15) as well as associations of anxiety and irritability symptoms measured cross-sectionally at age 15 with neural substrates of conflict and error processing assessed at age 15 using the flanker task. RESULTS: Results of whole-brain multivariate linear models revealed that anxiety at age 15 was uniquely associated with decreased neural response to conflict across multiple regions implicated in attentional control and conflict adaptation. Conversely, irritability at age 15 was uniquely associated with increased neural response to conflict in regions implicated in response inhibition. Developmental trajectories of anxiety and irritability interacted in relation to neural responses to both error and conflict. CONCLUSIONS: Our findings suggest that neural correlates of conflict processing may relate uniquely to anxiety and irritability. Continued cross-symptom research on the neural correlates of cognitive control could stimulate advances in individualized treatment for anxiety and irritability during child and adolescent development.

ADHD symptoms and diurnal cortisol in adolescents: The importance of comorbidities.

BACKGROUND: Altered regulation of diurnal cortisol has been associated with both dimensional symptoms and clinical diagnoses of attention deficit-hyperactivity disorder (ADHD). Indeed, a recent meta-analysis suggests that lower diurnal cortisol output may be a biomarker of attention deficit-hyperactivity disorder (ADHD); importantly, however, the influence of psychiatric comorbidities on this association has not been characterized. Approximately two-thirds of children with ADHD have at least one co-occurring neuropsychiatric condition, and altered HPA-axis function has been implicated in many of these conditions. Using dimensional measures of psychopathology, we examined whether comorbid symptoms influence the association of ADHD symptoms with daily cortisol output. METHODS: 138 adolescents (ages 11-15 years) completed measures of symptoms of psychopathology and provided saliva samples over two days. We analyzed whether ADHD symptoms were related to morning, afternoon, and evening cortisol, the cortisol awakening response (CAR) and cumulative daily cortisol (area under the curve with respect to ground [AUCg]) while accounting for symptoms of three psychiatric disorders that are commonly comorbid with ADHD: conduct disorder (CD), anxiety, and depression. In sensitivity analyses, we included symptoms of oppositional defiant disorder (ODD) in place of CD symptoms. FINDINGS: After controlling for symptoms of CD, anxiety, and depression, ADHD symptoms were associated significantly with higher cumulative diurnal cortisol (AUCg), morning cortisol, and afternoon cortisol. Symptoms of CD, anxiety and depression were not associated significantly with any cortisol metrics; however, in sensitivity analyses, ODD symptoms were associated with lower AUCg and morning cortisol. DISCUSSION: Our findings highlight the distinct influence of ADHD and externalizing symptoms on cortisol output. Further work is needed to examine the specificity of altered HPA-axis activity as a biomarker of ADHD and to elucidate whether symptoms of ADHD differ in their association with diurnal cortisol as a function of their severity.