Parametric Modulation of Neural Activity by Emotion in Youth With Bipolar Disorder, Youth With Severe Mood Dysregulation, and Healthy Volunteers

Abstract

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.

Impaired fixation to eyes during facial emotion labelling in children with bipolar disorder or severe mood dysregulation

“…18 Another study demonstrated that, while participants with BD and SMD exhibited similar deficits in amyg dala modulation in response to facial expressions of increasing anger intensity, the 2 patient groups exhibited different patterns of abnormalities in ventral visual pathway and frontoparietal activity. 17 Future work combining functional magnetic resonance imaging and eye tracking is needed to elucidate associations among neural dysfunction, impaired eye gaze and facial emotion labelling deficits in children with BD and SMD.…”

“…With regard to SMD, the neural dysfunction data are considerably more limited, although data do suggest both amygdala and parietal dysfunction. 17,18 The examination of visual scan patterns of emotional faces has been important to elucidate precise pathophysiological mechanisms of the aberrant face labelling behaviours across psychiatric disorders. In people with autism, [19][20][21][22] psychopathy 23 and schizophrenia, [24][25][26][27] each in comparison with healthy controls only, eye tracking studies have revealed associations between emotion labelling deficits and decreased attention to eyes.…”

Irritability in children and adolescents: past concepts, current debates, and future opportunities

“…The research on SMD focused on the differentiation from BD, and neuropsychological and imaging data comparing the two entities clarified its boundaries. 26,27 Furthermore, research on SMD stressed the importance of chronic irritability for developmental psychiatry and suggested its adoption by the DSM-5. In an epidemiological sample, lifetime prevalence for SMD was 3.3%.…”

Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

“…Actual literature suggests that changes in parietal activity in networks involving the amygdala might underlie dysfunctional affective processing [76].…”