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.
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