Loss of white matter integrity in major depressive disorder: Evidence using tract-based spatial statistical analysis of diffusion tensor imaging

Authors

  • Mayuresh S. Korgaonkar,

    1. The Brain Dynamics Centre, University of Sydney Medical School and Westmead Millennium Institute, Westmead, New South Wales, Australia
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    • M.S.K. and S.M.G. contributed equally to this work.

  • Stuart M. Grieve,

    Corresponding author
    1. The Brain Dynamics Centre, University of Sydney Medical School and Westmead Millennium Institute, Westmead, New South Wales, Australia
    2. Brain Resource International Database, Brain Resource Ltd., Ultimo, Sydney, New South Wales, Australia, and Suite 200, 1000 Sansome Street, San Francisco, California
    • The Brain Dynamics Centre, Acacia House, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia
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    • M.S.K. and S.M.G. contributed equally to this work.

  • Stephen H. Koslow,

    1. Brain Resource International Database, Brain Resource Ltd., Ultimo, Sydney, New South Wales, Australia, and Suite 200, 1000 Sansome Street, San Francisco, California
    2. American Foundation for Suicide Prevention, 120 Wall Street, 22nd Floor, New York City, New York
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  • John D.E. Gabrieli,

    1. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts
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  • Evian Gordon,

    1. Brain Resource International Database, Brain Resource Ltd., Ultimo, Sydney, New South Wales, Australia, and Suite 200, 1000 Sansome Street, San Francisco, California
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  • Leanne M. Williams

    1. The Brain Dynamics Centre, University of Sydney Medical School and Westmead Millennium Institute, Westmead, New South Wales, Australia
    2. Brain Resource International Database, Brain Resource Ltd., Ultimo, Sydney, New South Wales, Australia, and Suite 200, 1000 Sansome Street, San Francisco, California
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  • Conflicts of interest: S.H.K. and L.M.W. are small equity holders in Brain Resource Ltd. and have received consultancy fees for work unrelated to this study. E.G. is the CEO of Brain Resource Ltd. and has significant equity and stock options in the company.

  • The clinical trials registration identifier is NCT00693849.

Abstract

White matter (WM) has been shown to be affected in elderly patients with major depressive disorders (MDD). There is only limited evidence of WM structural abnormalities in nongeriatric MDD patients. This study investigates WM microstructural integrity in nongeriatric MDD patients recruited as part of the International Study to Predict Optimized Treatment in Depression clinical trial and establishes the validity of diffusion tensor imaging measures for the investigation of depression. Baseline diffusion tensor imaging data from 29 nongeriatric MDD participants (11 with melancholia) and 39 healthy control participants were used in this analysis. We performed tract-based spatial statistics analyses to evaluate WM microstructural integrity (1) between all healthy controls and all MDD participants, (2) between melancholic and nonmelancholic MDD participants, and (3) between each subgroup (melancholic and nonmelancholic) and controls. Significant WM integrity deficits were seen only for the melancholic MDD participants compared with controls. Compared with controls, melancholic participants showed an average reduction of 7.8% in fractional anisotropy over WM regions associated with the limbic system, dorsolateral prefrontal cortex, thalamic projection fibers, corpus callosum, and other association fibers. These fractional anisotropy deficits were also associated with decreased axial and increased radial diffusivity in these WM regions, suggesting a pattern of decreased myelination or other degeneration change. Our findings of WM structural abnormalities associated with the limbic system, the frontal cortex, and the thalamus support the prevailing theory of limbic-dorsolateral prefrontal cortex-thalamic dysfunction in depression. Our results also suggest that these deficits are most prominent in the melancholic subtype of MDD. Hum Brain Mapp, 2011. © 2010 Wiley Periodicals, Inc.

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