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Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder

Authors


  • JZK has financial interests/arrangements or affiliations with one or more organizations that could be perceived as a real or apparent conflict of interest. JZK has received grant/research support from Eli Lilly & Co.; has served as a consultant to AstraZeneca, Janssen-Ortho Inc., Wyeth Pharmaceuticals; and has received travel honoraria from Janssen-Ortho Inc., GlaxoSmithKline, Wyeth Pharmaceuticals. RSMcI has received research funding from Wyeth, GlaxoSmithKline, Merck, Servier, AstraZeneca; and has been a consultant and speaker for AstraZeneca, Eli Lilly & Co., Janssen-Ortho, Organon, Wyeth, Lundbeck, GlaxoSmithKline, Oryx, Biovail, Pfizer, Prestwick. SHK has received grant funding from AstraZeneca, Eli Lilly & Co., GlaxoSmithKline, Janssen-Ortho, Lundbeck and Merck Frosst; consultant fees from Advanced Neuromodulation Systems Inc., Biovail, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Janssen-Ortho, Lundbeck, Organon, Pfizer, Servier and Wyeth; and has received honoraria from Biovail, Eli Lilly & Co., GlaxoSmithKline, Janssen-Ortho, Lundbeck, Organon, Servier and Wyeth. JKS has received travel funds from Organon, Janssen and Wyeth. TAK has financial interests/arrangements or affiliations with one or more organizations that could be perceived as a real or apparent conflict of interest. TAK has received grant/research support from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eisai Inc., Elan Pharmaceuticals, Inc., Eli Lilly & Co., GlaxoSmithKline, Janssen Pharmaceutica Products LP, Novartis, Repligen Corp., Shire Pharmaceuticals Group plc., Solvay, Wyeth Pharmaceuticals; has served as a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Corcept Therapeutics, Elan Pharmaceuticals, Inc., Eli Lilly & Co., Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica Products LP, Jazz Pharmaceuticals, Merck & Co., Inc., Novartis, Pfizer, Repligen Corp., Shire Pharmaceuticals Group plc., Solvay, UCB Pharmaceuticals, Wyeth Pharmaceuticals; and has received lecture honoraria from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, Janssen Pharmaceutica Products LP, Novartis, Pfizer, Shire Pharmaceuticals Group plc. SR-T has no reported conflict of interest.

  • Disclosure information for all authors is listed before the references.

Corresponding author: Sidney H Kennedy, MD, FRCPC, University Health Network, 200 Elizabeth Street, Eaton North, 8th floor, Room 222, Toronto, ON, M5G 2C4 Canada. Fax: +1 416 340 4198; e-mail: sidney.kennedy@uhn.on.ca

Abstract

Background:  As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema.

Objective:  We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD).

Methods:  A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided.

Results:  While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD.

Conclusions:  Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.

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