title: Neurofunctional effects of quetiapine in patients with bipolar mania.
abstract: OBJECTIVE
  Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood.
  
  
  METHODS
  Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans.
  
  
  RESULTS
  At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003).
  
  
  CONCLUSIONS
  These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Davis
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|Center for Imaging Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: Eliassen
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Welge
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Blom
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|Center for Imaging Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Fleck
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Wade A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Jarvis
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Rummelhoff
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|Center for Imaging Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strakowski
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|Center for Imaging Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Adler
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate
keywords: bipolar disorder; fMRI; functional magnetic resonance imaging; mania; prefrontal cortex; quetiapine