Neural mechanisms of frustration in chronically irritable children.
ABSTRACT: OBJECTIVE:Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation. METHOD:The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions. RESULTS:Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group's responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups. CONCLUSIONS:In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.
Project description:OBJECTIVE:Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age. METHOD:The authors studied a transdiagnostic sample of 195 youths with varying levels of irritability (disruptive mood dysregulation disorder, N=52; anxiety disorder, N=42; attention deficit hyperactivity disorder, N=40; and healthy volunteers, N=61). Irritability was measured by parent and child reports on the Affective Reactivity Index. The fMRI paradigm was a cued-attention task differentiating neural activity in response to frustration (rigged feedback) from activity during attention orienting in the trial following frustration. RESULTS:Whole-brain activation analyses revealed associations with irritability during attention orienting following frustration. Irritability was positively associated with frontal-striatal activation, specifically in the dorsolateral prefrontal cortex, inferior frontal gyrus, and caudate. Age moderated the association between irritability and activation in some frontal and posterior regions (the anterior cingulate cortex, medial frontal gyrus, cuneus, precuneus, and superior parietal lobule [F=19.04-28.51, df=1, 189, partial eta squared=0.09-0.13]). Specifically, higher irritability was more strongly related to increased activation in younger youths compared with older youths. CONCLUSIONS:Following frustration, levels of irritability correlated with activity in neural systems mediating attention orienting, top-down regulation of emotions, and motor execution. Although most associations were independent of age, dysfunction in the anterior cingulate cortex and posterior regions was more pronounced in young children with irritability.
Project description:In recent years, increasing numbers of children have been diagnosed with bipolar disorder. In some cases, children with unstable mood clearly meet current diagnostic criteria for bipolar disorder, and in others, the diagnosis is unclear. Severe mood dysregulation is a syndrome defined to capture the symptomatology of children whose diagnostic status with respect to bipolar disorder is uncertain, that is, those who have severe, nonepisodic irritability and the hyperarousal symptoms characteristic of mania but who lack the well-demarcated periods of elevated or irritable mood characteristic of bipolar disorder. Levels of impairment are comparable between youths with bipolar disorder and those with severe mood dysregulation. An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood. Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups. No specific treatment for severe mood dysregulation currently exists, but verification of its identity as a syndrome distinct from bipolar disorder by further research should include treatment trials.
Project description:Irritability is an aspect of the negative affectivity domain of temperament, but in severe and dysregulated forms is a symptom of a range of psychopathologies. Better understanding of the neural underpinnings of irritability, outside the context of specific disorders, can help to understand normative variation but also characterize its clinical salience in psychopathology diagnosis. This study assessed brain activation during reward and frustration, domains of behavioral deficits in childhood irritability. Children (age 6-9) presenting in mental health clinics for extreme and impairing irritability (n = 26) were compared to healthy children (n = 28). Using developmentally sensitive methods, neural activation was measured via a negative mood induction paradigm during fMRI scanning. The clinical group displayed more activation of the anterior cingulate and middle frontal gyrus during reward, but less activation during frustration, than healthy comparison children. The opposite pattern was found in the posterior cingulate. Further, in clinical subjects, parent report of irritability was dimensionally related to decreased activation of the anterior cingulate and striatum during frustration. The results of this study indicate neural dysfunction within brain regions related to reward processing, error monitoring, and emotion regulation underlying clinically impairing irritability. Results are discussed in the context of a growing field of neuroimaging research investigating irritable children.
Project description:Irritability refers to a proneness for anger, and is a symptom of internalizing and externalizing psychopathology. Since irritability is associated with significant cross-sectional and longitudinal impairments, research on the behavioral and neural correlates of pediatric irritability in populations at risk for significant irritability is of paramount importance. Irritability can be assessed in the laboratory using behavioral paradigms that elicit frustration. Few behavioral frustration paradigms have been designed to measure the effects of frustration on cognitive control. Therefore, the goal of the present study was to validate a behavioral frustration paradigm for use in school-age children which addressed some of the limitations of prior research. Participants included children, ages 8-12 years, who were either typically developing (TD; n = 38) or diagnosed with attention-deficit/hyperactivity disorder (ADHD; n = 67), which provided a sample of children with a range of baseline irritability. All participants completed the Frustration Go/No-Go (GNG) task, and self-reported irritability was assessed using the Affective Reactivity Index. Results showed that across participants, self-reported frustration, commission error rate, and tau all increased with the addition of frustration, with similar effect sizes in ADHD and TD groups. Further, self-reported irritability, moreso than ADHD symptoms, predicted changes in self-reported frustration during the task. Together, these results support the construct validity of the Frustration GNG task as a means of assessing the effect of frustration on cognitive control. Clinical applications and future directions are discussed.
Project description:Irritability is a prominent feature of chronic mental disorders and a developmental marker of their early emergence. The most salient feature of irritability in early childhood is temper tantrums. While temper tantrums are normative in young children, they can be clinically concerning when they are dysregulated, very frequent, and/or occur in unexpected contexts. The present study uses behavioral and event-related brain potential (ERP) measures to characterize the relationship between irritability and neural markers of response inhibition in very young children. Forty-six children (ages 4-7 years) completed a go/no-go task under nonfrustrating and frustrating conditions. ERPs elicited by go and no-go stimuli were examined as a function of frustration condition and irritability, operationalized via the well-validated Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Higher Temper Loss scores were associated with larger N2no-go amplitudes and reduced no-go accuracy during frustration. This suggests that higher levels of irritability corresponded with increased conflict monitoring and poorer task performance during frustration. These findings add to a developing literature identifying the neurocognitive markers of varying levels of irritability in young children.
Project description:Nonepisodic irritability is a common and impairing problem, leading to the development of the diagnoses severe mood dysregulation (SMD) and disruptive mood dysregulation disorder (DMDD). No psychosocial therapies have been formally evaluated for either, with medication being the most common treatment. This study examined the feasibility and efficacy of a joint parent-child intervention for SMD.A total of 68 participants aged 7 to 12 years with attention-deficit/hyperactivity disorder (ADHD) and SMD were randomly assigned to the 11-week therapy or community-based psychosocial treatment. All participants were first stabilized on psychostimulant medication by study physicians. Of the participants, 56 still manifested impairing SMD symptoms and entered the therapy phase. Masked evaluators assessed participants at baseline, midpoint, and endpoint, with therapy participants reassessed 6 weeks later.All but 2 therapy participants attended the majority of sessions (n = 29), with families reporting high levels of satisfaction. The primary outcome of change in mood symptoms using the Mood Severity Index (MSI) did not reach significance except in the subset attending the majority of sessions (effect size = 0.53). Therapy was associated with significantly greater improvement in parent-rated irritability (effect size = 0.63). Treatment effects for irritability but not MSI diminished after therapy stopped. Little impact on ADHD symptoms was seen. Results may not be generalizable to youth with SMD and comorbidities different from those seen in this sample of children with ADHD, and are limited by the lack of a gold standard for measuring change in SMD symptoms.While failing to significantly improve mood symptoms versus community treatment, the integrative therapy was found to be a feasible and efficacious treatment for irritability in participants with SMD and ADHD.Group-Based Behavioral Therapy Combined With Stimulant Medication for Treating Children With Attention Deficit Hyperactivity Disorder and Impaired Mood; http://clinicaltrials.gov/; NCT00632619.
Project description:BACKGROUND:Compared to typically developing individuals, individuals with attention-deficit-hyperactivity disorder (ADHD) are on average more often exposed to stressful conditions (e.g., school failure, family conflicts, financial problems). We hypothesized that high exposure to stress relates to a more persistent and complex (i.e., multi-problem) form of ADHD, while low-stress exposure relates to remitting ADHD over the course of adolescence. METHOD:Longitudinal data (ages 11, 13, 16, and 19) came from the Tracking Adolescents' Individual Life Survey (TRAILS). We selected children diagnosed with ADHD (n = 244; 167 males; 77 females) from the TRAILS clinical cohort and children who screened positive (n = 365; 250 males; 115 females) and negative (gender-matched: n = 1222; 831 males; 391 females) for ADHD from the TRAILS general population sample cohort (total n = 1587). Multivariate latent class growth analysis was applied to parent- and self-ratings of stress exposure, core ADHD problems (attention problems, hyperactivity/impulsivity), effortful control, emotion dysregulation (irritability, extreme reactivity, frustration), and internalizing problems (depression, anxiety, somatic complaints). RESULTS:Seven distinct developmental courses in stress exposure and psychopathology were discerned, of which four related to ADHD. Two persistent ADHD courses of severely affected adolescents were associated with very high curvilinear stress exposure peaking in mid-adolescence: (1) Severe combined type with ongoing, severe emotional dysregulation, and (2) combined type with a high and increasing internalization of problems and elevated irritability; two partly remitting ADHD courses had low and declining stress exposure: (3) inattentive type, and (4) moderate combined type, both mostly without comorbid problems. CONCLUSIONS:High-stress exposure between childhood and young adulthood is strongly intertwined with a persistent course of ADHD and with comorbid problems taking the form of either severe and persistent emotion dysregulation (irritability, extreme reactivity, frustration) or elevated and increasing irritability, anxiety, and depression. Conversely, low and declining stress exposure is associated with remitting ADHD and decreasing internalizing and externalizing problems. Stress exposure is likely to be a facilitating and sustaining factor in these two persistent trajectories of ADHD with comorbid problems into young adulthood. Our findings suggest that a bidirectional, continuing, cycle of stressors leads to enhanced symptoms, in turn leading to more stressors, and so forth. Consideration of stressful conditions should, therefore, be an inherent part of the diagnosis and treatment of ADHD, to potentiate prevention and interruption of adverse trajectories.
Project description:Diagnostic criteria for disruptive mood dysregulation disorder (DMDD) require 1) periodic rageful outbursts and 2) disturbed mood (anger or irritability) that persists most of the time in between outbursts. Stimulant monotherapy, methodically titrated, often culminates in remission of severe aggressive behavior, but it is unclear whether those with persistent mood symptoms benefit less.This study examined the association between the presence of persistent mood disturbances and treatment outcomes among children with attention-deficit/hyperactivity disorder (ADHD) and periodic aggressive, rageful outbursts.Within a cohort of children with ADHD and aggressive behavior (n?=?156), the prevalence of persistent mood symptoms was evaluated at baseline and after completion of a treatment protocol that provided stimulant monotherapy and family-based behavioral treatment (duration mean [SD]?=?70.04 [37.83] days). The relationship of persistent mood symptoms on posttreatment aggressive behavior was assessed, as well as changes in mood symptoms.Aggressive behavior and periodic rageful outbursts remitted among 51% of the participants. Persistent mood symptoms at baseline did not affect the odds that aggressive behavior would remit during treatment. Reductions in symptoms of sustained mood disturbance accompanied reductions in periodic outbursts. Children who at baseline had high irritability but low depression ratings showed elevated aggression scores at baseline and after treatment; however, they still displayed large reductions in aggression.Among aggressive children with ADHD, aggressive behaviors are just as likely to decrease following stimulant monotherapy and behavioral treatment among those with sustained mood symptoms and those without. Improvements in mood problems are evident as well. Therefore, the abnormalities in persistent mood described by DMDD's criteria do not contraindicate stimulant therapy as initial treatment among those with comorbid ADHD. Rather, substantial improvements may be anticipated, and remission of both behavioral and mood symptoms seems achievable for a proportion of patients.ClinicalTrials.gov (U.S.); IDs: NCT00228046 and NCT00794625; www.clinicaltrials.gov.
Project description:Irritability and the new DSM-5 diagnostic category of Disruptive Mood Dysregulation Disorder (DMDD) have been conceptualised as related to mood disorder. Irritability is common in Attention Deficit Hyperactivity Disorder (ADHD) but little is known about its association with depression risk in this group. This study aims to establish levels of irritability and prevalence of DMDD in a clinical sample of children with ADHD, and examine their association with anxiety, depression and family history of depression.The sample consisted of 696 children (mean age 10.9 years) with a diagnosis of ADHD, recruited from UK child psychiatry and paediatric clinics. Parents completed the Child and Adolescent Psychiatric Assessment, a semi-structured diagnostic interview, about their child. This was used to establish prevalence of DMDD, anxiety disorder and depressive disorder, as well as obtain symptom scores for irritability, anxiety and depression. Questionnaires assessed current parental depression, and family history of depression.Irritability was common, with 91% endorsing at least one irritable symptom. 3-month DMDD prevalence was 31%. Children with higher levels of irritability or DMDD were more likely to have comorbid symptoms of anxiety, depression and a family history of depression.Results are based on a clinical sample, so may not be generalizable to children with ADHD in the general population.Irritability and DMDD were common, and were associated with markers of depression liability. Longitudinal studies are needed to examine the association between irritability and depression in youth with ADHD as they get older.
Project description:Disruptive mood dysregulation disorder (DMDD) was introduced as a new diagnostic entity under the category of depressive disorders in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). It was included in DSM-5 primarily to address concerns about the misdiagnosis and consequent overtreatment of bipolar disorder in children and adolescents. DMDD does provide a home for a large percentage of referred children with severe persistent irritability that did not fit well into any DSM, Fourth Edition (DSM-IV) diagnostic category. However, it has been a controversial addition to the DSM-5 due to lack of published validity studies, leading to questions about its validity as a distinct disorder. In this article, the authors discuss the diagnostic criteria, assessment, epidemiology, criticism of the diagnosis, and pathophysiology, as well as treatment and future directions for DMDD. They also review the literature on severe mood dysregulation, as described by the National Institute of Mental Health, as the scientific support for DMDD is based primarily on studies of severe mood dysregulation.