title: A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states.
abstract: OBJECTIVE
  Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally.
  
  
  METHODS
  fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole-brain functional connectivity analysis was performed using the left and right amygdala as seed regions.
  
  
  RESULTS
  Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group.
  
  
  CONCLUSIONS
  In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical-amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.
authors.affiliation: Division of Bipolar Disorders Research, Department of Psychiatry Center for Imaging Research, University of Cincinnati College of Medicine, Cincinnati, OH 45219-0516, USA. michael.cerullo@uc.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cerullo
authors.forename: David E
authors.initials: DE
authors.lastname: Fleck
authors.forename: James C
authors.initials: JC
authors.lastname: Eliassen
authors.forename: Matt S
authors.initials: MS
authors.lastname: Smith
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Adler
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strakowski
mesh_terms: D000679:Amygdala / Q000098:blood supply*; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000473:pathology*; D001931:Brain Mapping; D016000:Cluster Analysis; D003866:Depressive Disorder / Q000473:pathology*; D004644:Emotions / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D013223:Statistics as Topic
chemical_list: D010100:Oxygen