BackgroundIrritable mood has recently become a matter of intense scientific interest. Here, we present data from two samples, one from the United States and the other from the United Kingdom, demonstrating the clinical and research utility of the parent- and self-report forms of the Affective Reactivity Index (ARI), a concise dimensional measure of irritability.MethodsThe US sample (n = 218) consisted of children and adolescents recruited at the National Institute of Mental Health meeting criteria for bipolar disorder (BD, n = 39), severe mood dysregulation (SMD, n = 67), children at family risk for BD (n = 35), or were healthy volunteers (n = 77). The UK sample (n = 88) was comprised of children from a generic mental health setting and healthy volunteers from primary and secondary schools.ResultsParent- and self-report scales of the ARI showed excellent internal consistencies and formed a single factor in the two samples. In the US sample, the ARI showed a gradation with irritability significantly increasing from healthy volunteers through to SMD. Irritability was significantly higher in SMD than in BD by parent-report, but this did not reach significance by self-report. In the UK sample, parent-rated irritability was differentially related to emotional problems.ConclusionsIrritability can be measured using a concise instrument both in a highly specialized US, as well as a general UK child mental health setting.

Context Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show amygdala dysfunction during face emotion processing. However, studies have not compared such patients to each other and to comparison subjects in neural responsiveness to subtle changes in face emotion; the ability to process such changes is important for social cognition. We employed a novel parametrically designed faces paradigm. Objective Using a parametrically morphed emotional faces task, we compared activation in the amygdala and across the brain in BD, SMD, and healthy volunteers (HV). Design Case-control study. Setting Government research institute. Participants 57 youths (19 BD, 15 SMD, 23 HV). Main Outcome Measure Blood oxygenated level dependent (BOLD) data. Neutral faces were morphed with angry and happy faces in 25% intervals; static face stimuli appeared for 3000ms. Subjects performed hostility or non-emotional facial feature (i.e., nose width) ratings. Slope of BOLD activity was calculated across neutral-to-angry (N→A) and neutral-to-happy (N→H) face stimuli. Results In HV, but not BD or SMD, there was a positive association between left amygdala activity and anger on the face. In the N→H whole brain analysis, BD and SMD modulated parietal, temporal, and medial-frontal areas differently from each other and from HV; with increasing facial-happiness, SMD increased, while BD decreased, activity in parietal, temporal, and frontal regions. Conclusions Youth with BD or SMD differ from HV in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, BD and SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of face emotion processing in BD and SMD, suggesting these distinct clinical presentations may reflect differing pathologies along a mood disorders spectrum.

Objective Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparisons (HC), both BD subjects and youth at-risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder. Methods Amygdala activity was examined in 101 unrelated participants, 8-18 years old. Age, gender, and IQ-matched groups included BD (N=32), unaffected at-risk (N=13), and HC (N=56). During fMRI scanning, participants attended to emotional and non-emotional aspects of fearful and happy faces. Results While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity vs. HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring vs. sibling), presence of Axis I diagnosis (N=1 ADHD, 1 social phobia), and history of medication exposure (N=1) did not influence imaging findings. Conclusions We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth.

Background Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. Method During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. Results Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. Conclusions Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.