title: Time course of recovery showing initial prefrontal cortex changes at 16 weeks, extending to subcortical changes by 3 years in pediatric bipolar disorder.
abstract: OBJECTIVE
  Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD).
  
  
  METHODS
  Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge.
  
  
  RESULTS
  At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum.
  
  
  CONCLUSIONS
  Small sample size renders the present findings preliminary.
  
  
  CONCLUSIONS
  Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.
authors.affiliation: Pediatric Brain Research and Intervention Center, Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60608, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yang
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Lu
authors.forename: Minjie
authors.initials: M
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Stevens
authors.forename: Ezra
authors.initials: E
authors.lastname: Wegbreit
authors.forename: Jacklynn
authors.initials: J
authors.lastname: Fitzgerald
authors.forename: Bryn
authors.initials: B
authors.lastname: Levitan
authors.forename: Stewart
authors.initials: S
authors.lastname: Shankman
authors.forename: Mani N
authors.initials: MN
authors.lastname: Pavuluri
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D002648:Child; D003072:Cognition Disorders / Q000523:psychology; D004644:Emotions / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis
keywords: Emotion; Functional magnetic resonance imaging (fMRI); Pediatric bipolar disorder; Treatment effects