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White matter microstructural properties in bipolar disorder and its relationship to the spatial distribution of lithium in the brain

Joe Necus, Nishant Sinha, Fiona Elizabeth Smith, Peter Edward Thelwall, Carly Jay Flowers, Peter Neal Taylor, Andrew Matthew Blamire, David Andrew Cousins, Yujiang Wang
doi: https://doi.org/10.1101/346528
Joe Necus
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
2Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne, NE1 5TG, United Kingdom
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Nishant Sinha
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
2Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne, NE1 5TG, United Kingdom
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Fiona Elizabeth Smith
3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
4Newcastle Magnetic Resonance Centre, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom
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Peter Edward Thelwall
3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
4Newcastle Magnetic Resonance Centre, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom
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Carly Jay Flowers
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
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Peter Neal Taylor
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
2Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne, NE1 5TG, United Kingdom
5Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
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Andrew Matthew Blamire
3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
4Newcastle Magnetic Resonance Centre, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, United Kingdom
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David Andrew Cousins
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
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Yujiang Wang
1Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
2Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne, NE1 5TG, United Kingdom
5Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
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ABSTRACT

Background Lithium treatment is associated with an increase in magnetic resonance imaging derived measures of white matter integrity, but the relationship between the spatial distribution of brain lithium and white matter integrity is unknown.

Methods Euthymic patients with bipolar disorder receiving lithium treatment (n=12) and those on other medications but naïve to lithium (n=17) underwent diffusion imaging alongside matched healthy controls (n=16). Generalised fractional anisotropy (gFA) within white matter was compared between groups using a standard space white matter atlas. Lithium-treated patients also underwent novel multinuclear 3D lithium magnetic resonance imaging (7Li-MRI) to determine relative lithium concentration across the brain. The relationship between 7Li-MRI signal intensity and gFA was investigated at the resolution of the 7Li-MRI sequence in native space.

Results The lithium-treated bipolar disorder and healthy control groups had higher mean gFA in white matter than the bipolar disorder group treated with other medications but naïve to lithium (t = 2.5, p < 0.05; t = 2.7, p < 0.03, respectively). No differences in gFA were found between patients taking lithium and healthy controls (t = 0.02, p = 1). These effects were seen consistently across most regions in the white matter atlas. In the lithium-treated group, a significant effect of the 7Li-MRI signal in predicting the gFA (p < 0.01) was identified in voxels containing over 50% white matter.

Conclusions Lithium treatment of bipolar disorder is associated with higher gFA throughout brain white matter, and the spatial distribution of lithium is also positively associated with white matter gFA.

Footnotes

  • ↵† Co-senior authors

Copyright 
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Posted June 13, 2018.
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White matter microstructural properties in bipolar disorder and its relationship to the spatial distribution of lithium in the brain
Joe Necus, Nishant Sinha, Fiona Elizabeth Smith, Peter Edward Thelwall, Carly Jay Flowers, Peter Neal Taylor, Andrew Matthew Blamire, David Andrew Cousins, Yujiang Wang
bioRxiv 346528; doi: https://doi.org/10.1101/346528
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White matter microstructural properties in bipolar disorder and its relationship to the spatial distribution of lithium in the brain
Joe Necus, Nishant Sinha, Fiona Elizabeth Smith, Peter Edward Thelwall, Carly Jay Flowers, Peter Neal Taylor, Andrew Matthew Blamire, David Andrew Cousins, Yujiang Wang
bioRxiv 346528; doi: https://doi.org/10.1101/346528

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