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Cortical and subcortical white matter abnormalities in adults with remitted first-episode mania revealed by Tract-Based Spatial Statistics


  • RK has received compensation from AstraZeneca, Cyberonics, Gabriel Pharmaceuticals, Organon Pharmaceuticals, Otsuka, Pfizer, Saegis, Abbott, Acadia, BiolineRx, Bristol-Myers Squibb, Cephalon, Cortex, Dainippon Sumitomo Pharmaceutical, Eli Lilly & Co., Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Merck, Orexigen, Sanofi-aventis, Schering-Plough, Wyeth, and Xenoport. W-YC, G-LY, M-YC, P-SW, JL, Y-YS, WLN, and KS report no biomedical financial interests or potential conflicts of interest.

Corresponding author:
Dr. Kang Sim
Department of General Psychiatry
Woodbridge Hospital/Institute of Mental Health, Singapore
10, Buangkok View
Singapore 539747
Fax: (65) 63855900


Chan W-Y, Yang G-L, Chia M-Y, Woon P-S, Lee J, Keefe R, Sitoh Y-Y, Nowinski WL, Sim K. Cortical and subcortical white matter abnormalities in adults with remitted first-episode mania revealed by Tract-Based Spatial Statistics.
Bipolar Disord 2010: 12: 383–389. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first-episode mania and hypothesized that first-episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum).

Methods:  Diffusion tensor images were acquired from 16 patients with remitted first-episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract-Based Spatial Statistics.

Results:  Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum.

Conclusion:  Our findings highlighted that white matter abnormalities were present by the time of remission of first-episode mania. The widespread occurrence of these white matter abnormalities both in first-episode mania and chronic bipolar disorder suggested that disruption of white matter cortical-subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.