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Ellen Leibenluft - One of the best experts on this subject based on the ideXlab platform.
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Functional connectivity during frustration: a preliminary study of predictive modeling of Irritability in youth
Neuropsychopharmacology, 2021Co-Authors: Dustin Scheinost, Emily S Finn, Javid Dadashkarimi, Caroline G. Wambach, Caroline Macgillivray, Alexandra L. Roule, Tara A. Niendam, Daniel S. Pine, Melissa A. Brotman, Ellen LeibenluftAbstract:Irritability cuts across many pediatric disorders and is a common presenting complaint in child psychiatry; however, its neural mechanisms remain unclear. One core pathophysiological deficit of Irritability is aberrant responses to frustrative nonreward. Here, we conducted a preliminary fMRI study to examine the ability of functional connectivity during frustrative nonreward to predict Irritability in a transdiagnostic sample. This study included 69 youths (mean age = 14.55 years) with varying levels of Irritability across diagnostic groups: disruptive mood dysregulation disorder ( n = 20), attention-deficit/hyperactivity disorder ( n = 14), anxiety disorder ( n = 12), and controls ( n = 23). During fMRI, participants completed a frustrating cognitive flexibility task. Frustration was evoked by manipulating task difficulty such that, on trials requiring cognitive flexibility, “frustration” blocks had a 50% error rate and some rigged feedback, while “nonfrustration” blocks had a 10% error rate. Frustration and nonfrustration blocks were randomly interspersed. Child and parent reports of the affective reactivity index were used as dimensional measures of Irritability. Connectome-based predictive modeling, a machine learning approach, with tenfold cross-validation was conducted to identify networks predicting Irritability. Connectivity during frustration (but not nonfrustration) blocks predicted child-reported Irritability (ρ = 0.24, root mean square error = 2.02, p = 0.03, permutation testing, 1000 iterations, one-tailed). Results were adjusted for age, sex, medications, motion, ADHD, and anxiety symptoms. The predictive networks of Irritability were primarily within motor-sensory networks; among motor-sensory, subcortical, and salience networks; and between these networks and frontoparietal and medial frontal networks. This study provides preliminary evidence that individual differences in Irritability may be associated with functional connectivity during frustration, a phenotype-relevant state.
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phasic versus tonic Irritability differential associations with attention deficit hyperactivity disorder symptoms
Journal of the American Academy of Child and Adolescent Psychiatry, 2021Co-Authors: Elise M Cardinale, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft, Gabrielle F Freitag, Katharina KircanskiAbstract:Objective Irritability is a multifaceted construct in pediatric psychopathology. It has been conceptualized as having a phasic dimension and a tonic dimension. Disruptive mood dysregulation disorder is defined by the presence of both dimensions. Severe Irritability, or disruptive mood dysregulation disorder, is highly comorbid with attention-deficit/hyperactivity disorder (ADHD). However, it is unknown whether the presence of ADHD modulates the expression of phasic and tonic Irritability. Method A data-driven, latent variable approach was used to examine Irritability and ADHD symptoms in a transdiagnostic pediatric sample (N = 489) with primary disruptive mood dysregulation disorder, ADHD, subclinical Irritability symptoms, or no diagnosis. Using latent profile analyses, we identified 4 classes: high levels of both Irritability and ADHD symptoms, high levels of Irritability and moderate levels of ADHD symptoms, moderate levels of Irritability and high levels of ADHD symptoms, and low levels of both Irritability and ADHD symptoms. Confirmatory factor analysis operationalized phasic Irritability and tonic Irritability. Results As expected, the 2 latent classes characterized by high overall Irritability exhibited the highest levels of both phasic and tonic Irritability. However, between these 2 high Irritability classes, highly comorbid ADHD symptoms were associated with significantly greater phasic Irritability than were moderately comorbid ADHD symptoms. In contrast, the 2 high Irritability groups did not differ on levels of tonic Irritability. Conclusion These findings suggest that phasic, but not tonic, Irritability has a significant association with ADHD symptoms and that phasic and tonic might be distinct, though highly related, Irritability dimensions. Future research should investigate potential mechanisms underlying this differential association.
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developmental pathways to social anxiety and Irritability the role of the ern
Development and Psychopathology, 2020Co-Authors: Courtney Filippi, Ellen Leibenluft, Katharina Kircanski, David Pagliaccio, Anni R Subar, Jessica F Sachs, George A Buzzell, Rany Abend, Nathan A Fox, Daniel S. PineAbstract:Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and Irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and Irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood Irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and Irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early Irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood Irritability and blunted ERN predicted greater Irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.
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interaction of Irritability and anxiety on emotional responding and emotion regulation a functional mri study
Psychological Medicine, 2020Co-Authors: Soonjo Hwang, Ellen Leibenluft, Kathleen I Crum, Karina S Blair, Joseph Aloi, Harma Meffert, Stuart F White, Patrick M Tyler, Kayla PopeAbstract:Background Irritability and anxiety frequently co-occur in pediatric populations. Studies separately looking at the neural correlates of these symptoms have identified engagement of similar neural systems - particularly those implicated in emotional processing. Both Irritability and anxiety can be considered negative valence emotional states that might relate to emotion dysregulation. However, previous work has not examined the neural responding during the performance of an emotion regulation task as a function of interaction between Irritability and anxiety simultaneously. Methods This fMRI study involved 155 participants (90 with significant psychopathologies and 92 male) who performed the Affective Stroop Task, designed to engage emotion regulation as a function of task demands. The Affective Reactivity Index (ARI) was used to index Irritability and the Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to index anxiety. Results Levels of Irritability, but not anxiety, was positively correlated with responses to visual images within the right rostro-medial prefrontal cortex and left anterior cingulate cortex during view trials. The second region of ventral anterior cingulate cortex showed a condition-by-emotion-by-ARI score-by-SCARED score interaction. Specifically, anxiety level was significantly correlated with a decreased differential BOLD response to negative relative to neutral view trials but only in the presence of relatively high Irritability. Conclusions Atypical maintenance of emotional stimuli within the rostro-medial prefrontal cortex may exacerbate the difficulties faced by adolescents with Irritability. Moreover, increased anxiety combined with significant Irritability may disrupt an automatic emotional conflict-based form of emotion regulation that is particularly associated with the ventral anterior cingulate cortex.
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heritability stability and prevalence of tonic and phasic Irritability as indicators of disruptive mood dysregulation disorder
Journal of Child Psychology and Psychiatry, 2019Co-Authors: Ashlee A. Moore, Melissa A. Brotman, Ellen Leibenluft, Dana M Lapato, Steven H Aggen, John M Hettema, Timothy P York, Judy L Silberg, Roxann RobersonnayAbstract:BACKGROUND Little is known about genetic and environmental influences on the components of disruptive mood dysregulation disorder (DMDD), tonic Irritability (i.e., irritable mood) and phasic Irritability (i.e., temper outbursts). This study examined prevalence, stability, and heritability of tonic Irritability, phasic Irritability, and a DMDD proxy (pDMDD) based on DSM-5 criteria. METHODS pDMDD was derived using data from clinical interviews of parents and their twins (N = 1,431 twin pairs), ages 8-17, participating in Waves 1 and 2 of the Virginia Twin Study of Adolescent Behavioral Development. Biometrical modeling was used to compare a common pathway model (CPM) and an independent pathway model (IPM), and heritability estimates were obtained for pDMDD using the symptoms of irritable mood (tonic Irritability; DMDD Criterion D), intense temper outbursts (phasic Irritability; DMDD Criterion A), and frequent temper outbursts (phasic Irritability; DMDD Criterion C). RESULTS Lifetime prevalence of pDMDD was 7.46%. The stability of DMDD symptoms and the pDMDD phenotype across approximately one year were moderate (.30-.69). A CPM was a better fit to the data than an IPM. Phasic Irritability loaded strongly onto the pDMDD latent factor (.89-.96) whereas tonic Irritability did not (.28). Genetic influences accounted for approximately 59% of the variance in the latent pDMDD phenotype, with the remaining 41% of the variance due to unique environmental effects. The heritability of tonic Irritability (54%) was slightly lower than that of frequent and intense temper (components of phasic Irritability; 61% and 63%, respectively). CONCLUSIONS Compared to tonic Irritability, phasic Irritability appears to be slightly more stable and heritable, as well as a stronger indicator of the latent factor. Furthermore, environmental experiences appear to play a substantial role in the development of Irritability and DMDD, and researchers should seek to elucidate these mechanisms in future work.
Argyris Stringaris - One of the best experts on this subject based on the ideXlab platform.
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How and Why Are Irritability and Depression Linked
Child and adolescent psychiatric clinics of North America, 2021Co-Authors: Pablo Vidal-ribas, Argyris StringarisAbstract:Based on its course over time, Irritability is linked to depression cross-sectionally and longitudinally. Cross-sectionally, Irritability takes an episodic form as a symptom in pediatric depression; yet, Irritability in the absence of depressed mood or anhedonia is rare. Longitudinally, chronic Irritability has been shown to predict depression rather than bipolar disorder or externalizing disorders. Evidence suggests that the link between Irritability and depression is explained mostly by shared genetic risk. Both conditions are also associated with higher rates of family history of depression, childhood temperaments and personality styles, and negative parenting styles. The treatment implications are discussed.
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A Prospective Study of Rumination and Irritability in Youth.
Journal of abnormal child psychology, 2020Co-Authors: Eleanor Leigh, Ailsa Lee, H. M. Brown, Simone Pisano, Argyris StringarisAbstract:Although youth Irritability is linked with substantial psychiatric morbidity and impairment, little is known about how personal characteristics influence its course. In this study we examined the prospective associations between angry and depressive rumination and Irritability. A sample of 165 school pupils aged 12-14 years were assessed at two time points six months apart. They completed measures of Irritability at Times 1 and 2 and depressive and angry rumination at Time 1. In line with our hypotheses, we found that angry rumination is significantly associated with Irritability six months later, over and above baseline Irritability and depressive rumination. The present findings suggest angry rumination is relevant to the genesis of Irritability in adolescents, and point to possible routes for prevention and early intervention.
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Irritability in ADHD: association with later depression symptoms.
European child & adolescent psychiatry, 2019Co-Authors: Olga Eyre, Ellen Leibenluft, Argyris Stringaris, Lucy Riglin, Stephan Collishaw, Anita ThaparAbstract:Attention-deficit/hyperactivity disorder (ADHD) and depression commonly co-occur. Identifying children with ADHD at risk for later depression may allow early intervention and prevention. Irritability is one possible mechanism linking these two disorders. It is common in ADHD and associated with later depression in the general population. Cross-sectional studies suggest an association between Irritability and depression in ADHD, but longitudinal research is limited. This study followed up a clinical ADHD sample longitudinally to examine: (1) the association between childhood Irritability and later depression symptoms, and (2) whether Irritability persistence is important in this association. At baseline, parents (n = 696) completed semi-structured interviews about their child (mean age = 10.9), providing information on child psychopathology, including Irritability. A subsample (n = 249) was followed up after a mean of 5.4 years. Parent-completed Mood and Feelings Questionnaires provided information on depressive symptoms at follow-up. Parent-rated structured diagnostic interviews provided information on ADHD diagnosis and Irritability at follow-up. Regression analyses examined associations between (i) baseline Irritability and depression symptoms at follow-up, and (ii) persistent (vs. remitted) Irritability and depression symptoms at follow-up. Analyses controlled for age, gender, depression symptoms, anxiety, ADHD symptoms, and ADHD medication at baseline. Baseline Irritability was associated with depression symptoms at follow-up, but the association attenuated after controlling for anxiety and ADHD symptoms. Persistent Irritability was associated with depression symptoms at follow-up, after including all covariates. Children with ADHD with persistent Irritability are at elevated risk of developing depression symptoms. They may be a target for early intervention and prevention of depression.
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Irritability in Pediatric Psychopathology - Irritability in Mood and Anxiety Disorders
Irritability in Pediatric Psychopathology, 2019Co-Authors: Pablo Vidal-ribas Belil, Argyris StringarisAbstract:Irritability is common in children and adolescents presenting with mood and anxiety disorders and was recently introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a diagnostic category under the name of disruptive mood dysregulation disorder (DMDD). The aim of this chapter is to describe the distinct phenomenology, epidemiology, and correlates of Irritability in the context of bipolar disorder, DMDD, depression, and anxiety disorders. The course of Irritability is episodic in bipolar disorder and depression and is commonly accompanied by elated and depressed mood, respectively. In contrast, the Irritability seen in DMDD is chronic and recurrent. In anxiety disorders, the experience of Irritability is usually related to the presence of the feared situation. Regardless of these differences, Irritability seems to be associated with higher rates of comorbidity and greater functional impairment and may need attention in its own right.
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practitioner review definition recognition and treatment challenges of Irritability in young people
Journal of Child Psychology and Psychiatry, 2018Co-Authors: Argyris Stringaris, Melissa A. Brotman, Pablo Vidalribas, Ellen LeibenluftAbstract:Background Irritability is one of the most common reasons for referral to child and adolescent mental health services and is the main characteristic of the new diagnosis of disruptive mood dysregulation disorder (DMDD). However, the recognition and management of Irritability presents a major challenge in clinical practice and may be partly responsible for the dramatic increase in antipsychotic prescribing in recent years. Methods In this review, we provide up-to-date information on the definition and mechanisms underlying Irritability, and its assessment in clinical practice. We aim to discuss the latest research on DMDD, and the presence of severe Irritability in the context of other disorders, as well as to recommend a treatment algorithm. Results Severe Irritability is associated with aberrant reward processing and bias toward threatening stimuli. Several measures are available to easily assess Irritability. The recent diagnosis of DMDD captures children whose main problem is severe Irritability and differ from those with bipolar disorder in longitudinal outcomes, family history, and behavioral and neural correlates. Treatment of Irritability might depend on the context it appears. Indirect evidence suggests that parent management training (PMT) and cognitive behavioral therapy (CBT) are the most supported psychological treatments for Irritability. Conclusions Irritability, recognized as a mood problem rather than a purely behavioral manifestation, is a common condition for young people. Practitioners should not ignore Irritability as it is associated with substantial morbidity and impairment. Although there are no trials with Irritability as main outcome, clinicians can apply several existing pharmacological and psychological interventions for its treatment. Also, new promising approaches relying on pathophysiological findings, such as exposure-based cognitive behavioral therapy techniques and interpretation bias training (IBT), are being currently investigated.
Daniel S. Pine - One of the best experts on this subject based on the ideXlab platform.
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Functional connectivity during frustration: a preliminary study of predictive modeling of Irritability in youth
Neuropsychopharmacology, 2021Co-Authors: Dustin Scheinost, Emily S Finn, Javid Dadashkarimi, Caroline G. Wambach, Caroline Macgillivray, Alexandra L. Roule, Tara A. Niendam, Daniel S. Pine, Melissa A. Brotman, Ellen LeibenluftAbstract:Irritability cuts across many pediatric disorders and is a common presenting complaint in child psychiatry; however, its neural mechanisms remain unclear. One core pathophysiological deficit of Irritability is aberrant responses to frustrative nonreward. Here, we conducted a preliminary fMRI study to examine the ability of functional connectivity during frustrative nonreward to predict Irritability in a transdiagnostic sample. This study included 69 youths (mean age = 14.55 years) with varying levels of Irritability across diagnostic groups: disruptive mood dysregulation disorder ( n = 20), attention-deficit/hyperactivity disorder ( n = 14), anxiety disorder ( n = 12), and controls ( n = 23). During fMRI, participants completed a frustrating cognitive flexibility task. Frustration was evoked by manipulating task difficulty such that, on trials requiring cognitive flexibility, “frustration” blocks had a 50% error rate and some rigged feedback, while “nonfrustration” blocks had a 10% error rate. Frustration and nonfrustration blocks were randomly interspersed. Child and parent reports of the affective reactivity index were used as dimensional measures of Irritability. Connectome-based predictive modeling, a machine learning approach, with tenfold cross-validation was conducted to identify networks predicting Irritability. Connectivity during frustration (but not nonfrustration) blocks predicted child-reported Irritability (ρ = 0.24, root mean square error = 2.02, p = 0.03, permutation testing, 1000 iterations, one-tailed). Results were adjusted for age, sex, medications, motion, ADHD, and anxiety symptoms. The predictive networks of Irritability were primarily within motor-sensory networks; among motor-sensory, subcortical, and salience networks; and between these networks and frontoparietal and medial frontal networks. This study provides preliminary evidence that individual differences in Irritability may be associated with functional connectivity during frustration, a phenotype-relevant state.
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phasic versus tonic Irritability differential associations with attention deficit hyperactivity disorder symptoms
Journal of the American Academy of Child and Adolescent Psychiatry, 2021Co-Authors: Elise M Cardinale, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft, Gabrielle F Freitag, Katharina KircanskiAbstract:Objective Irritability is a multifaceted construct in pediatric psychopathology. It has been conceptualized as having a phasic dimension and a tonic dimension. Disruptive mood dysregulation disorder is defined by the presence of both dimensions. Severe Irritability, or disruptive mood dysregulation disorder, is highly comorbid with attention-deficit/hyperactivity disorder (ADHD). However, it is unknown whether the presence of ADHD modulates the expression of phasic and tonic Irritability. Method A data-driven, latent variable approach was used to examine Irritability and ADHD symptoms in a transdiagnostic pediatric sample (N = 489) with primary disruptive mood dysregulation disorder, ADHD, subclinical Irritability symptoms, or no diagnosis. Using latent profile analyses, we identified 4 classes: high levels of both Irritability and ADHD symptoms, high levels of Irritability and moderate levels of ADHD symptoms, moderate levels of Irritability and high levels of ADHD symptoms, and low levels of both Irritability and ADHD symptoms. Confirmatory factor analysis operationalized phasic Irritability and tonic Irritability. Results As expected, the 2 latent classes characterized by high overall Irritability exhibited the highest levels of both phasic and tonic Irritability. However, between these 2 high Irritability classes, highly comorbid ADHD symptoms were associated with significantly greater phasic Irritability than were moderately comorbid ADHD symptoms. In contrast, the 2 high Irritability groups did not differ on levels of tonic Irritability. Conclusion These findings suggest that phasic, but not tonic, Irritability has a significant association with ADHD symptoms and that phasic and tonic might be distinct, though highly related, Irritability dimensions. Future research should investigate potential mechanisms underlying this differential association.
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developmental pathways to social anxiety and Irritability the role of the ern
Development and Psychopathology, 2020Co-Authors: Courtney Filippi, Ellen Leibenluft, Katharina Kircanski, David Pagliaccio, Anni R Subar, Jessica F Sachs, George A Buzzell, Rany Abend, Nathan A Fox, Daniel S. PineAbstract:Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and Irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and Irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood Irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and Irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early Irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood Irritability and blunted ERN predicted greater Irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.
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multi method assessment of Irritability and differential linkages to neurophysiological indicators of attention allocation to emotional faces in young children
Developmental Psychobiology, 2020Co-Authors: Christen M Deveney, Daniel S. Pine, Lauren S Wakschlag, Damion J Grasso, Amy Hsu, Christopher R Estabrook, Elvira Zobel, James L Burns, Margaret J BriggsgowanAbstract:Facilitated attention toward angry stimuli (attention bias) may contribute to anger proneness and temper outbursts exhibited by children with high Irritability. However, most studies linking attention bias and Irritability rely on behavioral measures with limited precision and no studies have explored these associations in young children. The present study explores Irritability-related attention biases toward anger in young children (N = 128; ages 4-7 years) engaged in a dot-probe task with emotional faces, as assessed with event-related brain potential (ERP) indices of early selective attention and multi-method assessment of Irritability. Irritability assessed via semi-structured clinical interview predicted larger anterior N1 amplitudes to all faces. In contrast, Irritability assessed via a laboratory observation paradigm predicted reduced P1 amplitudes to angry relative to neutral faces. These findings suggest that altered early attentional processing occurs in young children with high Irritability; however, the nature of these patterns may vary with methodological features of the Irritability assessments. Future investigations using different assessment tools may provide greater clarity regarding the underlying neurocognitive correlates of Irritability. Such studies may also contribute to the ongoing debates about how to best define and measure Irritability across the developmental spectrum in a manner that is most informative for linkage to neural processes.
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exposure therapy for pediatric Irritability theory and potential mechanisms
Behaviour Research and Therapy, 2019Co-Authors: Katharina Kircanski, Daniel S. Pine, Ellen Leibenluft, Michelle G Craske, Bruno B Averbeck, Melissa A. BrotmanAbstract:Abstract Pediatric Irritability is prevalent and impairing, yet little is known about its pathophysiology and treatment. In this article, we build on our and others' previous work to posit core mechanisms of Irritability operating across the brain, behavior, and environment. Specifically, we propose proximal processes that surround the symptomatology of Irritability and are potential targets for an exposure-based cognitive-behavioral therapy (CBT) for Irritability that our group has developed. The heart of this model focuses on neurocognitive processes: youth's encoding of nonreward and threat stimuli, which involves prediction error signaling in the brain, and cognitive control in the context of frustration. Alterations in these processes are theorized to be central to chronic, severe Irritability. Environmental responses to youth's symptom expression are also examined. Exposure-based CBT for Irritability utilizes controlled, in vivo exposure to nonreward and threat stimuli with the aim to engage cognitive control and target top-down regulation of frustration. This intervention integrates selected parent management training techniques to target symptom reinforcement processes. Continued pathophysiological and treatment studies of Irritability will not only refine our emerging understanding of the phenotype, but also inform broader questions on the brain and behavioral mechanisms of CBT efficacy.
Melissa A. Brotman - One of the best experts on this subject based on the ideXlab platform.
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Functional connectivity during frustration: a preliminary study of predictive modeling of Irritability in youth
Neuropsychopharmacology, 2021Co-Authors: Dustin Scheinost, Emily S Finn, Javid Dadashkarimi, Caroline G. Wambach, Caroline Macgillivray, Alexandra L. Roule, Tara A. Niendam, Daniel S. Pine, Melissa A. Brotman, Ellen LeibenluftAbstract:Irritability cuts across many pediatric disorders and is a common presenting complaint in child psychiatry; however, its neural mechanisms remain unclear. One core pathophysiological deficit of Irritability is aberrant responses to frustrative nonreward. Here, we conducted a preliminary fMRI study to examine the ability of functional connectivity during frustrative nonreward to predict Irritability in a transdiagnostic sample. This study included 69 youths (mean age = 14.55 years) with varying levels of Irritability across diagnostic groups: disruptive mood dysregulation disorder ( n = 20), attention-deficit/hyperactivity disorder ( n = 14), anxiety disorder ( n = 12), and controls ( n = 23). During fMRI, participants completed a frustrating cognitive flexibility task. Frustration was evoked by manipulating task difficulty such that, on trials requiring cognitive flexibility, “frustration” blocks had a 50% error rate and some rigged feedback, while “nonfrustration” blocks had a 10% error rate. Frustration and nonfrustration blocks were randomly interspersed. Child and parent reports of the affective reactivity index were used as dimensional measures of Irritability. Connectome-based predictive modeling, a machine learning approach, with tenfold cross-validation was conducted to identify networks predicting Irritability. Connectivity during frustration (but not nonfrustration) blocks predicted child-reported Irritability (ρ = 0.24, root mean square error = 2.02, p = 0.03, permutation testing, 1000 iterations, one-tailed). Results were adjusted for age, sex, medications, motion, ADHD, and anxiety symptoms. The predictive networks of Irritability were primarily within motor-sensory networks; among motor-sensory, subcortical, and salience networks; and between these networks and frontoparietal and medial frontal networks. This study provides preliminary evidence that individual differences in Irritability may be associated with functional connectivity during frustration, a phenotype-relevant state.
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phasic versus tonic Irritability differential associations with attention deficit hyperactivity disorder symptoms
Journal of the American Academy of Child and Adolescent Psychiatry, 2021Co-Authors: Elise M Cardinale, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft, Gabrielle F Freitag, Katharina KircanskiAbstract:Objective Irritability is a multifaceted construct in pediatric psychopathology. It has been conceptualized as having a phasic dimension and a tonic dimension. Disruptive mood dysregulation disorder is defined by the presence of both dimensions. Severe Irritability, or disruptive mood dysregulation disorder, is highly comorbid with attention-deficit/hyperactivity disorder (ADHD). However, it is unknown whether the presence of ADHD modulates the expression of phasic and tonic Irritability. Method A data-driven, latent variable approach was used to examine Irritability and ADHD symptoms in a transdiagnostic pediatric sample (N = 489) with primary disruptive mood dysregulation disorder, ADHD, subclinical Irritability symptoms, or no diagnosis. Using latent profile analyses, we identified 4 classes: high levels of both Irritability and ADHD symptoms, high levels of Irritability and moderate levels of ADHD symptoms, moderate levels of Irritability and high levels of ADHD symptoms, and low levels of both Irritability and ADHD symptoms. Confirmatory factor analysis operationalized phasic Irritability and tonic Irritability. Results As expected, the 2 latent classes characterized by high overall Irritability exhibited the highest levels of both phasic and tonic Irritability. However, between these 2 high Irritability classes, highly comorbid ADHD symptoms were associated with significantly greater phasic Irritability than were moderately comorbid ADHD symptoms. In contrast, the 2 high Irritability groups did not differ on levels of tonic Irritability. Conclusion These findings suggest that phasic, but not tonic, Irritability has a significant association with ADHD symptoms and that phasic and tonic might be distinct, though highly related, Irritability dimensions. Future research should investigate potential mechanisms underlying this differential association.
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heritability stability and prevalence of tonic and phasic Irritability as indicators of disruptive mood dysregulation disorder
Journal of Child Psychology and Psychiatry, 2019Co-Authors: Ashlee A. Moore, Melissa A. Brotman, Ellen Leibenluft, Dana M Lapato, Steven H Aggen, John M Hettema, Timothy P York, Judy L Silberg, Roxann RobersonnayAbstract:BACKGROUND Little is known about genetic and environmental influences on the components of disruptive mood dysregulation disorder (DMDD), tonic Irritability (i.e., irritable mood) and phasic Irritability (i.e., temper outbursts). This study examined prevalence, stability, and heritability of tonic Irritability, phasic Irritability, and a DMDD proxy (pDMDD) based on DSM-5 criteria. METHODS pDMDD was derived using data from clinical interviews of parents and their twins (N = 1,431 twin pairs), ages 8-17, participating in Waves 1 and 2 of the Virginia Twin Study of Adolescent Behavioral Development. Biometrical modeling was used to compare a common pathway model (CPM) and an independent pathway model (IPM), and heritability estimates were obtained for pDMDD using the symptoms of irritable mood (tonic Irritability; DMDD Criterion D), intense temper outbursts (phasic Irritability; DMDD Criterion A), and frequent temper outbursts (phasic Irritability; DMDD Criterion C). RESULTS Lifetime prevalence of pDMDD was 7.46%. The stability of DMDD symptoms and the pDMDD phenotype across approximately one year were moderate (.30-.69). A CPM was a better fit to the data than an IPM. Phasic Irritability loaded strongly onto the pDMDD latent factor (.89-.96) whereas tonic Irritability did not (.28). Genetic influences accounted for approximately 59% of the variance in the latent pDMDD phenotype, with the remaining 41% of the variance due to unique environmental effects. The heritability of tonic Irritability (54%) was slightly lower than that of frequent and intense temper (components of phasic Irritability; 61% and 63%, respectively). CONCLUSIONS Compared to tonic Irritability, phasic Irritability appears to be slightly more stable and heritable, as well as a stronger indicator of the latent factor. Furthermore, environmental experiences appear to play a substantial role in the development of Irritability and DMDD, and researchers should seek to elucidate these mechanisms in future work.
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exposure therapy for pediatric Irritability theory and potential mechanisms
Behaviour Research and Therapy, 2019Co-Authors: Katharina Kircanski, Daniel S. Pine, Ellen Leibenluft, Michelle G Craske, Bruno B Averbeck, Melissa A. BrotmanAbstract:Abstract Pediatric Irritability is prevalent and impairing, yet little is known about its pathophysiology and treatment. In this article, we build on our and others' previous work to posit core mechanisms of Irritability operating across the brain, behavior, and environment. Specifically, we propose proximal processes that surround the symptomatology of Irritability and are potential targets for an exposure-based cognitive-behavioral therapy (CBT) for Irritability that our group has developed. The heart of this model focuses on neurocognitive processes: youth's encoding of nonreward and threat stimuli, which involves prediction error signaling in the brain, and cognitive control in the context of frustration. Alterations in these processes are theorized to be central to chronic, severe Irritability. Environmental responses to youth's symptom expression are also examined. Exposure-based CBT for Irritability utilizes controlled, in vivo exposure to nonreward and threat stimuli with the aim to engage cognitive control and target top-down regulation of frustration. This intervention integrates selected parent management training techniques to target symptom reinforcement processes. Continued pathophysiological and treatment studies of Irritability will not only refine our emerging understanding of the phenotype, but also inform broader questions on the brain and behavioral mechanisms of CBT efficacy.
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Anxious-Irritable Children: A Distinct Subtype of Childhood Anxiety?
Behavior therapy, 2019Co-Authors: Yaara Shimshoni, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft, Eli R. Lebowitz, Wendy K. SilvermanAbstract:Children with anxiety disorders often present with other co-occurring symptom clusters, of which Irritability is among the most highly co-occurring. Despite compelling clinical and pathophysiological evidence linking anxiety and Irritability, little is known regarding the clinical presentation and associated impairment of children with both anxiety and Irritability. In this study, our aims were to confirm the preponderance of Irritability in clinically anxious children and compare clinically anxious children with Irritability to those without Irritability across sociodemographic, clinical, psychosocial, and family domains. Participants were 230 children with anxiety disorders (ages 6-14 years) and their mothers, and 91 healthy controls (ages 6-17 years) and their mothers. Of the clinically anxious children, 121 were anxious and irritable; 109 were anxious but not irritable. Irritability levels were significantly higher in the clinically anxious children compared with the healthy controls. Children with anxiety disorders and Irritability presented with greater severity and impairment across clinical phenomenology, psychosocial, and family domains relative to anxious children without Irritability. Regression analysis findings were convergent in that greater severity and impairment across these same domains predicted higher Irritability levels in the children with anxiety disorders. Results support the meaningful distinction between anxious children with and without Irritability. Implications of the findings are discussed particularly in regard to assessment and treatment and future research directions are delineated.
Jillian Lee Wiggins - One of the best experts on this subject based on the ideXlab platform.
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Neural mechanisms of reward processing in adolescent Irritability.
Developmental psychobiology, 2021Co-Authors: Maria Kryza-lacombe, Lea R. Dougherty, Lauren S Wakschlag, Brianna Hernandez, Cassidy Owen, Richard C. Reynolds, Jillian Lee WigginsAbstract:Irritability is impairing and prevalent across pediatric psychiatric disorders and typical development, yet its neural mechanisms are largely unknown. This study evaluated the relation between adolescent Irritability and reward-related brain function as a candidate neural mechanism. Adolescents from intervention-seeking families in the community (N = 52; mean age = 13.80, SD = 1.94) completed a monetary incentive delay task to assess reward anticipation and feedback (reward receipt and omission) during fMRI acquisition. Whole-brain analyses, controlling for age, examined brain activation and striatal and amygdala connectivity in relation to Irritability. Irritability was measured using the parent- and youth-reported Affective Reactivity Index. Irritability was associated with altered reward processing-related activation and connectivity in multiple networks during reward anticipation and feedback, including increased striatal activation and altered ventral striatum connectivity with prefrontal areas. Our findings suggest that Irritability is associated with altered neural patterns during reward processing and that aberrant prefrontal cortex-mediated top-down control may be related to Irritability. These findings inform our understanding of the etiology of youth Irritability and the development of mechanism-based interventions.
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face emotion processing in pediatric Irritability neural mechanisms in a sample enriched for Irritability with autism spectrum disorder
Journal of the American Academy of Child and Adolescent Psychiatry, 2020Co-Authors: Maria Kryzalacombe, Natalia Iturri, Christopher S Monk, Jillian Lee WigginsAbstract:Objective Characterizing the pathophysiology of Irritability symptoms from a dimensional perspective above and beyond diagnostic boundaries is key to developing mechanism-based interventions that can be applied broadly. Face emotion processing deficits are present in youths with elevated levels of Irritability. The present study aimed to identify the neural mechanisms of face emotion processing in a sample enriched for Irritability by including youths with high-functioning autism spectrum disorder (HF-ASD). Method Youths (N = 120, age = 8.3−19.2 years) completed an implicit face emotion task during functional magnetic resonance imaging. We evaluated how Irritability, measured dimensionally, above and beyond diagnostic group, relates to whole-brain neural activation and amygdala connectivity in response to face emotions. Results Both neural activation and amygdala connectivity differed as a function of Irritability level and face emotion in the prefrontal cortex. Youths with higher Irritability levels had decreased activation in response to both fearful and happy faces in the left middle frontal gyrus and to happy faces in the left inferior frontal gyrus. Furthermore, increased Irritability levels were associated with altered right amygdala connectivity to the left superior frontal gyrus when viewing fearful and sad faces. Conclusion The neural mechanisms of face emotion processing differ in youths with higher Irritability compared to their less irritable peers. The findings suggest that these Irritability mechanisms may be common to both typically developing and HF-ASD youths. Understanding the neural mechanisms of pediatric Irritability symptoms that cut across diagnostic boundaries may be leveraged for future intervention development.
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Irritability in Pediatric Psychopathology - Irritability Development from Middle Childhood Through Adolescence: Trajectories, Concurrent Conditions, and Outcomes
Irritability in Pediatric Psychopathology, 2019Co-Authors: Cynthia Kiefer, Jillian Lee WigginsAbstract:The current review traces the longitudinal course of pediatric Irritability from middle childhood through adulthood. Irritability is a symptom dimension characterized by angry mood and temper outbursts and is fairly common in middle childhood through adolescence. While Irritability generally demonstrates some decline over time, both clinical and normative levels of Irritability in middle childhood predict functional impairment and internalizing and externalizing symptoms through adolescence. The link between pediatric Irritability and internalizing symptoms persists into adulthood. Pediatric Irritability uniquely predicts suicidality in addition to adult psychopathology and impairment. Despite the serious consequences of pediatric Irritability across development, there are few effective treatments for Irritability. Taken together, these studies suggest that focus on early treatment and prevention of Irritability symptoms in childhood may help mitigate lasting negative outcomes in adulthood.
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preschool and school age Irritability predict reward related brain function
Journal of the American Academy of Child and Adolescent Psychiatry, 2018Co-Authors: Lea R. Dougherty, Karen T G Schwartz, Maria Kryzalacombe, Jill Weisberg, Philip Spechler, Jillian Lee WigginsAbstract:Objective Although chronic Irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to play a role in Irritability. The current study aimed to identify how the developmental timing of Irritability during preschool- and school-age relates to reward-related brain function during school-age. Method Children’s Irritability was assessed during the preschool period (wave 1; ages 3.0−5.9 years) and 3 years later (wave 2; ages 5.9−9.6 years) using a clinical interview. At wave 2, children (N = 46; 28 female and 18 male) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during functional magnetic resonance imaging. Results Children with more versus less severe preschool Irritability, controlling for concurrent Irritability, exhibited altered reward-related connectivity: right amygdala with insula and inferior parietal lobe as well as left ventral striatum with lingual gyrus, postcentral gyrus, superior parietal lobe, and culmen. Children with more versus less severe concurrent Irritability, controlling for preschool Irritability, exhibited a similar pattern of altered connectivity between left and right amygdalae and superior frontal gyrus and between left ventral striatum and precuneus and culmen. Neural differences associated with Irritability were most evident between reward and no-reward conditions when participants missed the target. Conclusion Preschool-age Irritability and concurrent Irritability were uniquely associated with aberrant patterns of reward-related connectivity, highlighting the importance of developmental timing of Irritability for brain function.
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identifying clinically significant Irritability in early childhood
Journal of the American Academy of Child and Adolescent Psychiatry, 2018Co-Authors: Jillian Lee Wiggins, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft, Margaret J Briggsgowan, Ryne Estabrook, Lauren S WakschlagAbstract:Objective Advances in developmentally sensitive measurement have enabled differentiation of normative versus clinically salient Irritability in early childhood. However, clinical application of these measures is still nascent. The authors developed an optimized model of clinically salient irritable behaviors at preschool age. Based on this model, the authors derived an empirically based cutoff in relation to concurrent DSM-5 Irritability-related disorders (i.e., oppositional defiant disorder, disruptive mood dysregulation disorder, other depressive disorders) and used longitudinal models to test the predictive validity of the cutoff for impairment and Irritability trajectories and later DSM disorders. Method Preschool children oversampled for Irritability were followed over 3 time points into early school age (N = 425; mean age at baseline 4.7 years, mean follow-up 2.9 years). Mothers reported on children’s Irritability using the developmentally validated Multidimensional Assessment of Profile of Disruptive Behavior (MAP-DB) Temper Loss scale, impairment using the Family Life Impairment Scale, and DSM categories using the Preschool Age Psychiatric Assessment and the Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version. Results Of 22 MAP-DB Temper Loss behaviors, 2 behaviors—1 normative (easily frustrated) and 1 rare dysregulated (destructive tantrums)—were uniquely related to cross-domain impairment. At baseline, these 2 Irritability items identified diagnostic status (oppositional defiant disorder, disruptive mood dysregulation disorder, other depressive disorders) with good sensitivity (70–73%) and specificity (74–83%). Children above the Irritability cutoff at baseline also exhibited more persistent Irritability and impairment and greater likelihood of DSM disorders in early school age. Conclusion Clinical identification of early-onset Irritability can be enhanced using brief, developmentally optimized indicators. Further research to apply these findings to tiered early intervention is important.
