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Progressive neurostructural changes in adolescent and adult patients with bipolar disorder

Authors


  • MPD reports research support from AstraZeneca, Eli Lilly & Co., Johnson & Johnson, Shire, Janssen, Pfizer, Bristol-Myers Squibb, Repligen, Martek, Somerset, GlaxoSmithKline, and Sumitomo; has participated in lecture bureaus for Bristol-Myers Squibb and Merck; and has consulted for GlaxoSmithKline, Eli Lilly & Co., Merck, and Bristol-Myers Squibb. SMS reports research support from Eli Lilly & Co., Janssen, AstraZeneca, Martek Biosciences, Nutrition 21, and Repligen; and has consulted for CME Outfitters, Adamed, Consensus Medical Communications (CME through the University of Minnesota; unrestricted grant from Ortho McNeil/Janssen), and Web MD. CMA reports research support from AstraZeneca, Eli Lilly & Co., Johnson & Johnson, Shire, Janssen, Pfizer, Bristol-Myers Squibb, Repligen, Martek, Somerset, GlaxoSmithKline, and Sumitomo; and participation in a lecture bureau and consultation for Merck. MEL, KBJ, NPM, WAW, and DF do not have any conflicts of interest to disclose.

Corresponding author:
Caleb M. Adler, M.D.
Department of Psychiatry and Behavioral Neuroscience
University of Cincinnati
260 Stetson Street, Suite 3200
Cincinnati, OH 45219-0516, USA
Fax: 513-558-3399
E-mail: adlercb@ucmail.uc.edu

Abstract

Lisy ME, Jarvis KB, DelBello MP, Mills NP, Weber WA, Fleck D, Strakowski SM, Adler CM. Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.
Bipolar Disord 2011: 13: 396–405. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  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.

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