title: Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.
abstract: OBJECTIVE
  Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time.
  
  
  METHODS
  A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3-34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects.
  
  
  RESULTS
  We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures.
  
  
  CONCLUSIONS
  Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age.
authors.affiliation: Division of Bipolar Disorder Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219-0516, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lisy
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Jarvis
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
authors.forename: Neil P
authors.initials: NP
authors.lastname: Mills
authors.forename: Wade A
authors.initials: WA
authors.lastname: Weber
authors.forename: David
authors.initials: D
authors.lastname: Fleck
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strakowski
authors.forename: Caleb M
authors.initials: CM
authors.lastname: Adler
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D055815:Young Adult