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.

Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N=20), SMD (N=18), and HV (N=22) during “Aware” and ”Non-aware” priming of shapes by emotional faces. Subjects rated how much they liked the shape. In Aware, a face (angry, fearful, happy, neutral, blank oval) appeared (187ms) before the shape. In Non-Aware, a face appeared (17ms), followed by a mask (170ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders.

Objective Bipolar disorder (BD) is highly debilitating in both children and adults. Child and adult BD patients show both behavioral deficits in face emotion processing and abnormal amygdala activation. However, amygdala function in pediatric vs. adult BD patients has never been compared directly. Method This study compared amygdala responses to emotional facial expressions in 74 subjects [pediatric (N=18) and adult (N=17) patients with BD, healthy volunteer (HV) children (N=15) and adults (N=22)]. Subjects performed a gender identification task while viewing fearful, angry, and neutral faces. Results In response to fearful faces, patients with BD across age-groups showed right amygdala hyperactivity relative to healthy volunteers. However, when responses to all facial expressions were combined, pediatric patients exhibited greater right amygdala activation than either adults with BD or HV children. Conclusions Amygdala hyperactivity in response to fearful faces is present in both youths and adults with BD. However, compared to adults with BD or healthy youths, youths with BD show amygdala hyperactivity in response to a broad array of emotional faces. Thus, abnormal amygdala activation during face processing appears to be more pervasive in children than adults with BD.

IntroductionSevere mood disorders in children, specifically bipolar disorder (BD) and severe mood dysregulation (SMD), have recently received increased attention, as researchers and clin icians acknowledge the substantial impairment and treatment needs of these populations. The BD and SMD phenotypes differ in that BD is characterized by distinct episodes of mania (and, frequently, depression), whereas SMD is characterized by severe, chronic, impairing irritability.1 Importantly, however, the 2 phenotypes are similar in that both are severe pediatric mood disorders that share Background: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces. Methods: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions. Results: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls. Limitations: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns. Conclusion: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study.