title: Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with psychosis history.
abstract: BACKGROUND
  Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This might occur due to both disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested whether regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Furthermore, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who might exhibit a more severe clinical course.
  
  
  METHODS
  We collected resting-state functional magnetic resonance imaging at 3T in 68 remitted bipolar I patients (34 with psychosis history) and 51 demographically matched healthy participants. We employed a recently developed global brain connectivity method, restricted to PFC (rGBC). We also independently tested connectivity between anatomically defined amygdala and PFC.
  
  
  RESULTS
  Bipolar patients exhibited reduced medial prefrontal cortex (mPFC) rGBC, increased amygdala-mPFC connectivity, and reduced connectivity between amygdala and dorsolateral PFC. All effects were driven by psychosis history. Moreover, the magnitude of observed effects was significantly associated with lifetime psychotic symptom severity.
  
  
  CONCLUSIONS
  This convergence between rGBC, seed-based amygdala findings, and symptom severity analyses highlights that mPFC, a core emotion regulation region, exhibits both within-PFC dysconnectivity and connectivity abnormalities with limbic structures in bipolar illness. Furthermore, lateral PFC dysconnectivity in patients with psychosis history converges with published work in schizophrenia, indicating possible shared risk factors. Observed dysconnectivity in remitted patients suggests a bipolar trait characteristic and might constitute a risk factor for phasic features of the disorder.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, Yale University, New Haven, CT 06519, USA. alan.anticevic@yale.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Anticevic
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Brumbaugh
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Winkler
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Lombardo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barrett
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Corlett
authors.forename: Hedy
authors.initials: H
authors.lastname: Kober
authors.forename: June
authors.initials: J
authors.lastname: Gruber
authors.forename: Grega
authors.initials: G
authors.lastname: Repovs
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cole
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000150:complications / Q000503:physiopathology; D012720:Severity of Illness Index