Neural Mechanisms of Frustration in Chronically Irritable Children

National Institute of Mental Health (NIMH), 베서스다, Maryland, United States
American Journal of Psychiatry (Impact Factor: 12.3). 06/2013; 170(10). DOI: 10.1176/appi.ajp.2013.12070917
Source: PubMed


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.

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.

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.

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.

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    • "Probably secondary to this broad classification , there had been a dramatic rise in rates of pediatric BP from the mid-1990s to the early 2000s (Krieger et al. 2013) along with debates about the ''true'' phenotype of pediatric BP (Parry and Richards 2014; Stringaris and Youngstrom 2014). Further studies revealed that episodic and chronic irritability in youth had distinct consequences and etiologies (Stringaris et al. 2009; Deveney et al. 2013). Accordingly, it was posited that severe, episodic irritability in childhood correlated with BP in adulthood (Brotman et al. 2007; Copeland et al. 2014), whereas severe, chronic irritability in childhood correlated with unipolar depression and anxiety disorders (Stringaris et al. 2009). "
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    ABSTRACT: Objective: Disruptive mood dysregulation disorder (DMDD) is a novel diagnosis listed in Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) to encompass chronic and impairing irritability in youth, and to help its differentiation from bipolar disorders. Because it is a new entity, treatment guidelines, as well as its sociodemographic and clinical features among diverse populations, are still not elucidated. Here, DMDD cases from three centers in Turkey are reported and the implications are discussed. Methods: The study was conducted at the Abant Izzet Baysal University Medical Faculty Department of Child and Adolescent Psychiatry (Bolu), and American Hospital and Bengi Semerci Institute (Istanbul) between August 2014 and October 2014. Records of patients were reviewed and features of patients who fulfilled criteria for DMDD were recorded. Data were analyzed with SPS Version 17.0 for Windows. Descriptive analyses, χ(2) test, and Mann-Whitney U test were used for analyses. Diagnostic consensus was determined via Cohen's κ constants. p was set at 0.01. Results: Thirty-six patients (77.8 % male) fulfilled criteria for DMDD. κ value for consensus between clinicians was 0.68 (p = 0.00). Mean age of patients was 9.0 years (S.D. = 2.5) whereas the mean age of onset for DMDD symptoms was 4.9 years (S.D. = 2.2). Irritability, temper tantrums, verbal rages, and physical aggression toward family members were the most common presenting complaints. Conclusions: Diagnostic consensus could not be reached for almost one fourth of cases. Most common reasons for lack of consensus were problems in clarification of moods of patients in between episodes, problems in differentiation of normality and pathology (i.e., symptoms mainly reported in one setting vs. pervasiveness), and inability to fulfill frequency criterion for tantrums.
    Journal of child and adolescent psychopharmacology 10/2015; DOI:10.1089/cap.2015.0004 · 2.93 Impact Factor
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    • "Here, we extend those findings by demonstrating that such between-group differences in neural activity are present even when the faces are processed outside awareness. Data in the current experiment are consistent with previous neuroimaging and clinical studies, which conclude that severe, nonepisodic irritability does not appear to be a developmental presentation of BD (Brotman et al., 2006, 2010; Rich et al., 2007; Adleman et al., 2011; Deveney et al., 2012; Thomas et al., 2012, 2013). Further, our data indicate that patients and healthy subjects may differ in their neural responses to emotional stimuli, even when they are not aware of those stimuli. "

    53rd Annual Meeting of the American-College-of-Neuropsychopharmacology; 12/2014
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    • "RSC may additionally be more ecologically valid, allowing observation of mind wandering, a commonly occurring activity in the daily lives of youth. In addition, by focusing on neural regions shown to be important in fMRI task-related analyses [such as the amygdala (Altshuler et al., 2005; Foland et al., 2008), striatum (Deveney et al., 2013), prefrontal cortical (Pavuluri et al., 2008; Kalmar et al., 2009; Passarotti et al., 2010; Ladouceur et al., 2011) and anterior cingulate cortical (Gogtay et al., 2007; Kalmar et al., 2009) regions, and an insula-centered neural network supporting salience, interoception, and emotion perception (Rubia et al., 2009; Taylor et al., 2009; Kurth et al., 2010; Cauda et al., 2012; Cloutman et al., 2012)], RSC studies may increase our understanding of pathophysiologic processes in behaviorally and emotionally dysregulated youth. "
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    ABSTRACT: The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 11/2014; 231(1). DOI:10.1016/j.pscychresns.2014.10.015 · 2.42 Impact Factor
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