Brendan A. Rich

Amygdala Activation During Emotion Processing of Neutral Faces in Children With Severe Mood Dysregulation Versus ADHD or Bipolar Disorder

OBJECTIVE To understand disorder-unique and common pathophysiology, studies in multiple patient groups with overlapping symptoms are needed. Deficits in emotion processing and hyperarousal symptoms are prominent features of bipolar disorder, attention deficit hyperactivity disorder (ADHD), and severe mood dysregulation. The authors compared amygdala response during emotional and nonemotional ratings of neutral faces in youths with these disorders as well as a group of healthy comparison youths. METHOD Blood-oxygen-level-dependent (BOLD) signal in the amygdala was examined in children with bipolar disorder (N=43), ADHD (N=18), and severe mood dysregulation (N=29) and healthy comparison subjects (N=37). During functional magnetic resonance imaging (fMRI), participants attended to emotional and nonemotional aspects of neutral faces. RESULTS While rating subjective fear of neutral faces, youths with ADHD demonstrated left amygdala hyperactivity relative to the other three groups, whereas youths with severe mood dysregulation demonstrated hypoactivity. CONCLUSIONS These findings support the role of unique neural correlates in face-emotion processing among youths with bipolar disorder, ADHD, and severe mood dysregulation.

Facial Emotion Labeling Deficits in Children and Adolescents at Risk for Bipolar Disorder

OBJECTIVE Research has revealed facial emotion labeling deficits in children and adolescents with bipolar disorder. To assess whether such impairments may be an endophenotype for bipolar disorder, the authors examined facial emotion identification proficiency in children who were at risk for bipolar disorder because they had a first-degree relative with the illness. METHOD The facial expressions subtests of the Diagnostic Analysis of Nonverbal Accuracy scale were administered to 52 patients with bipolar disorder, 24 at-risk youths, and 78 control subjects, all 4-18 years of age. RESULTS Compared with the control group, both the bipolar and at-risk groups made more errors identifying facial emotions. The number of errors did not differ significantly between the bipolar and at-risk groups. CONCLUSIONS Deficits in facial emotion labeling may be a risk marker for bipolar disorder. Further study is needed to determine the neural mechanisms involved, as well as to explore other emotional processing impairments in youths at risk for bipolar disorder and to identify genetic associations.

Neural connectivity in children with bipolar disorder: impairment in the face emotion processing circuit.

BACKGROUND Pediatric bipolar disorder (BD), a highly debilitating illness, is characterized by amygdala abnormalities, i.e., volume reduction and hyperactivation during face processing. Evidence of perturbed amygdala functional connectivity with other brain regions would implicate a distributed neural circuit in the pathophysiology of BD, and would further elucidate the neural mechanisms associated with BD face emotion misinterpretation. METHODS Thirty-three BD and 24 healthy age, gender, and IQ-matched subjects completed a functional magnetic resonance imaging (fMRI) task of face emotion identification in which attention was directed to emotional (hostility, fearfulness) and nonemotional (nose width) aspects of faces. Voxel-wise analyses examined whole brain functional connectivity with the left amygdala. RESULTS Compared to healthy subjects, BD subjects had significantly reduced connectivity between the left amygdala and two regions: right posterior cingulate/precuneus and right fusiform gyrus/parahippocampal gyrus. Deficits were evident regardless of mood state and comorbid diagnoses. CONCLUSIONS BD youth exhibit deficient connectivity between the amygdala and temporal association cortical regions previously implicated in processing facial expressions and social stimuli. In conjunction with previously documented volumetric and functional perturbations in these brain regions, dysfunction in this distributed neural circuit may begin to clarify the pathophysiology of the face emotion misperceptions and social deficits seen in BD youth.

Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation

Children with narrow phenotype bipolar disorder (NP-BD; i.e., history of at least one hypomanic or manic episode with euphoric mood) are deficient when labeling face emotions. It is unknown if this deficit is specific to particular emotions, or if it extends to children with severe mood dysregulation (SMD; i.e., chronic irritability and hyperarousal without episodes of mania). Thirty-nine NP-BD, 31 SMD, and 36 control subjects completed the emotional expression multimorph task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust). Groups were compared in terms of intensity of emotion required before identification occurred and accuracy. Both NP-BD and SMD youth required significantly more morphs than controls to label correctly disgusted, surprised, fearful, and happy faces. Impaired face labeling correlated with deficient social reciprocity skills in NP-BD youth and dysfunctional family relationships in SMD youth. Compared to controls, patients with NP-BD or SMD require significantly more intense facial emotion before they are able to label the emotion correctly. These deficits are associated with psychosocial impairments. Understanding the neural circuitry associated with face-labeling deficits has the potential to clarify the pathophysiology of these disorders.

Further Psychometric Evaluation of the Eyberg and Behar Rating Scales for Parents and Teachers of Preschoolers.

The psychometric properties of two parent behavior rating scales, the Eyberg Child Behavior Inventory (ECBI) and the Preschool Behavior Questionnaire – Parent-Completed (PBQ-P), and two teacher rating scales, the Sutter-Eyberg Student Behavior Inventory (SESBI) and the Preschool Behavior QuestionnaireTeacher-Completed (PBQ-T) were examined in a homogeneous community sample of 88 preschool children between 2 and 6 years of age.

Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation.

OBJECTIVE The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal, a syndrome defined as severe mood dysregulation (SMD) by Leibenluft, has been the focus of increasing concern. We conducted the first randomized double-blind, placebo-controlled trial in SMD youth, choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects. METHODS SMD youths 7-17 years were tapered off their medications. Those who continued to meet SMD criteria after a 2-week, single-blind, placebo run-in were randomized to a 6-week double-blind trial of either lithium (n = 14) or placebo (n = 11). Clinical outcome measures were: (1) Clinical Global Impressions-Improvement (CGI-I) score less than 4 at trials end and (2) the Positive and Negative Syndrome Scale (PANSS) factor 4 score. Magnetic resonance spectroscopy (MRS) outcome measures were myoinositol (mI), N-acetyl-aspartate (NAA), and combined glutamate/glutamine (GLX), all referenced to creatine (Cr). RESULTS In all, 45% (n = 20/45) of SMD youths were not randomized due to significant clinical improvement during the placebo run-in. Among randomized patients, there were no significant between-group differences in either clinical or MRS outcome measures. CONCLUSION Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths, further SMD treatment trials are warranted given its prevalence.

Risk for Bipolar Disorder is Associated with Face-Processing Deficits across Emotions.

OBJECTIVE Youths with euthymic bipolar disorder (BD) have a deficit in face-emotion labeling that is present across multiple emotions. Recent research indicates that youths at familial risk for BD, but without a history of mood disorder, also have a deficit in face-emotion labeling, suggesting that such impairments may be an endophenotype for BD. It is unclear whether this deficit in at-risk youths is present across all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BD become manifest. METHOD Thirty-seven patients with pediatric BD, 25 unaffected children with a first-degree relative with BD, and 36 typically developing youths were administered the Emotional Expression Multimorph Task, a computerized behavioral task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust). RESULTS Repeated-measures analysis of covariance revealed that, compared with the control youths, the patients and the at-risk youths required significantly more intense emotional information to identify and correctly label face emotions. The patients with BD and the at-risk youths did not differ from each other. Group-by-emotion interactions were not significant, indicating that the group effects did not differ based on the facial emotion. CONCLUSIONS The youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness. Further research is needed to determine whether such deficits meet all the criteria for an endophenotype.

The Impact of Reward, Punishment, and Frustration on Attention in Pediatric Bipolar Disorder

BACKGROUND Theories in affective neuroscience suggest that mood disorders involve perturbations in attention-emotion interactions. We tested the hypothesis that frustration adversely impacts attention and behavior in children with bipolar disorder (BPD). METHODS Thirty-five children with BPD and 26 normal control subjects completed: 1) a Posner attention task with feedback but no contingencies; 2) an affective Posner with contingencies; and 3) an affective Posner that used rigged feedback to induce frustration. Reaction time (RT) and event-related potential (ERP) data were collected. RESULTS At baseline (task 1), there were no between-group differences in behavior or ERPs. Children with BPD exhibited reduced parietal P3 amplitude on task 3 only. On trials occurring after negative feedback, control subjects showed decreased RT when contingencies were introduced (task 2), whereas BPD subjects did not. CONCLUSIONS The introduction of contingencies was associated with impaired performance of children with BPD, suggesting deficits in their ability to adapt to changing contingencies. In addition, frustration was associated with disrupted attention allocation in children with BPD. We hypothesize that children with BPD inappropriately deployed attention to their internal frustration rather than to the task, causing impaired performance.

Impaired probabilistic reversal learning in youths with mood and anxiety disorders

BACKGROUND From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. We sought to determine the specificity of previously demonstrated reversal learning impairments in youths with bipolar disorder (BD) by now comparing BD youths to those with severe mood dysregulation (SMD), major depressive disorder (MDD), anxiety (ANX), and healthy controls. METHOD We administered the probabilistic response reversal (PRR) task to 165 pediatric participants aged 7-17 years with BD (n=35), SMD (n=35), ANX (n=42), MDD (n=18) and normal controls (NC; n=35). Our primary analysis compared PRR performance across all five groups matched for age, sex and IQ. RESULTS Compared to typically developing controls, probabilistic reversal learning was impaired in BD youths, with a trend in those with MDD (p=0.07). CONCLUSIONS Our results suggest that reversal learning deficits are present in youths with BD and possibly those with MDD. Further work is necessary to elucidate the specificity of neural mechanisms underlying such behavioral deficits.

Perception of Facial Emotion in Adults with Bipolar or Unipolar Depression and Controls

Previous research indicates that patients with depression display deficits in their ability to perceive emotions. However, few studies have used animated facial stimuli or explored sensitivity to facial expressions in depressed individuals. Moreover, limited research is available on facial processing in unipolar versus bipolar depression. In this study, 34 patients with DSM-IV major depressive disorder (MDD), 21 patients with DSM-IV bipolar disorder (BPD) in the depressed phase, and 24 never-depressed controls completed the Emotional Expression Multimorph Task, which presents facial emotions in gradations from neutral to 100% emotional expression (happy, sad, surprised, fearful, angry, and disgusted). Groups were compared in terms of sensitivity and accuracy in identifying emotions. Our preliminary findings suggest that subjects with bipolar depression may have emotional processing abnormalities relative to controls.