Neural Responses to Intranasal Oxytocin in Youths With Severe Irritability.

OBJECTIVE: The authors investigated the neural impact of intranasal oxytocin on emotion processing areas in youths with severe irritability in the context of disruptive mood and behavior disorders. METHODS: Fifty-two participants with severe irritability, as measured by a score ≥4 on the Affective Reactivity Index (ARI), with diagnoses of disruptive behavior disorders (DBDs) and/or disruptive mood dysregulation disorder (DMDD) were randomly assigned to treatment with intranasal oxytocin or placebo daily for 3 weeks. Assessments were conducted at baseline and at the end of the trial; the primary outcomes were measures of irritability on the ARI and ratings on the Clinical Global Impressions severity scale (CGI-S) focusing on DBD and DMDD symptoms, and secondary outcomes included the CGI improvement scale (CGI-I) and ratings of proactive and reactive aggressive behavior on the Reactive-Proactive Aggression Questionnaire. Forty-three participants (22 in the oxytocin group and 21 in the placebo group) completed pre- and posttreatment functional MRI (fMRI) scans with the affective Stroop task. RESULTS: Youths who received oxytocin showed significant improvement in CGI-S and CGI-I ratings compared with those who received placebo. In the fMRI data, blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex were significantly reduced after oxytocin compared with placebo. These BOLD response changes were correlated with improvement in clinical severity. CONCLUSIONS: This study provides initial and preliminary evidence that intranasal oxytocin may induce neural-level changes in emotion processing in youths with irritability in the context of DBDs and DMDD. This may lead to symptom and severity changes in irritability.

Mediating effect of amygdala activity on response to fear vs. happiness in youth with significant levels of irritability and disruptive mood and behavior disorders.

Introduction: Irritability, characterized by a tendency to exhibit increased anger, is a common clinical problem in youth. Irritability is a significant clinical issue in youth with various psychiatric diagnoses, especially disruptive behavior, and mood disorders (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, and Disruptive Mood Dysregulation Disorder). Although there have been previous studies focusing on functional alteration in the amygdala related to irritability, there is no comprehensive model between emotional, neuronal, and behavioral characteristics. Methods: Using an functional magnetic resonance imaging (fMRI) procedure, we investigated the relationships between behavioral irritability, selective impairments in processing facial emotions and the amygdala neural response in youth with increased irritability. Fifty-nine youth with disruptive mood and behavior disorder completed a facial expression processing task with an event-related fMRI paradigm. The severity of irritability was evaluated using the Affective Reactivity Index. Results: In the result of behavioral data, irritability, and reaction time (RT) differences between interpreting negative (fear) and positive (happiness) facial expressions were positively correlated. In the fMRI result, youth showed higher activation in the right cingulate gyrus, bilateral cerebellum, right amygdala, right precuneus, right superior frontal gyrus, right middle occipital gyrus, and middle temporal gyrus, during the happiness condition vs. fear condition. No brain region exhibited greater activation in the fear than in the happiness conditions. In the result of the mediator analysis, increased irritability was associated with a longer RT toward positive vs. negative facial expressions. Irritability was also positively associated with the difference in amygdala blood oxygen level-dependent responses between the two emotional conditions (happiness > fear). This difference in amygdala activity mediated the interaction between irritability and the RT difference between negative and positive facial expressions. Discussion: We suggest that impairment in the implicit processing of facial emotional expressions with different valences causes distinct patterns of amygdala response, which correlate with the level of irritability. These results broaden our understanding of the biological mechanism of irritability at the neural level and provide information for the future direction of the study.

Research Audit on Clinical Utility of Dimensional Disruptive Mood and Behavior Psychopathologies in Child and Adolescent Psychiatry Practice.

To investigate the utility of dimensional psychopathologies of disruptive mood and behavior disorders (DBDs) by applying latent profile analysis (LPA) for characterization of youth referred to the tertiary outpatient clinic of child and adolescent psychiatry clinic and pharmacological treatment choices. One hundred fifty-eight children and adolescents with significant DBDs symptoms participated. Core dimensional psychopathologies of DBDs (irritability, callous-unemotional trait, and reactive-proactive aggressive behavior), DSM diagnoses, prescribed medications, and behavioral and emotional problems (Child Behavior Checklist, CBCL) were measured at baseline (clinic intake) and at 3-month follow-up. Latent Profile Analysis (LPA) was applied to characterize the study population based on the levels and interrelations among the core dimensional DBDs psychopathologies. Following LPA, the differences in clinical and treatment features between the latent classes were analyzed. LPA revealed two latent classes based on severity of DBDs symptoms. Class 1 (the moderate group) was characterized by relatively low scores on all trans-diagnostic indicators, whereas class 2 (the severe/critical group) showed higher levels of the dimensional psychopathologies and the majority of CBCL subscales. In addition, the severe/critical group was more often prescribed antipsychotic medications, and also experienced more frequent medication changes (addition, increasing the dose, and trial of different medications). Our findings suggested that application of LPA to a cluster of dimensional DBDs psychopathologies may provide valuable characterization of the youths referred to a tertiary outpatient child and adolescent psychiatric clinic, and offer insight into the providers' decision making on psychotropic medications, by overall severity of these psychopathologies rather than by single categorical diagnosis or single externalizing psychopathology.

Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability.

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Effectiveness of Stimulant Medications on Disruptive Behavior and Mood Problems in Young Children.

OBJECTIVE: There are very few studies on the effectiveness of stimulant medications for the treatment of disruptive mood and behavior problems in young children (less than 7 years) with Disruptive Behavior Disorders (DBD). The current study aims to determine whether young children (ages 4-7) in a long-term, intensive outpatient behavioral treatment program who are receiving stimulant medications show greater improvement in mood and behavior problems compared to peers who did not. METHODS: A retrospective chart review was conducted for 97 participants diagnosed with DBD, aged 4-7 years old who were enrolled in an intensive outpatient behavioral intervention program. Pre- and post-intervention Child Behavior Checklist (CBCL) scores for disruptive behavior and mood problems were compared between the children who received stimulant medications and those who did not. RESULTS: Paired t tests showed a statistically significant improvement in CBCL outcomes between pre- and post-intervention scores of disruptive behavior and mood problems. ANCOVA analysis, however, showed no clear further improvement in those same CBCL scores in the participants who received stimulant medications compared to the participants who did not. CBCL scores for Conduct Disorder were marginally significant for less improvement for the participants who received stimulant medications. CONCLUSION: This retrospective review suggests a possibility that stimulant medications may not provide additional benefit for the long-term treatment of disruptive behavior and mood problems in young children under age 7. Future study is warranted to evaluate the efficacy/effectiveness of stimulant medications in the treatment of disruptive behavior and mood problems in this population.