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

Lookup NU author(s): Joe NecusORCiD, Nishant Sinha, Dr Fiona Smith, Professor Peter Thelwall, Carly Flowers, Dr Peter TaylorORCiD, Professor Andrew BlamireORCiD, Dr David Cousins, Dr Yujiang WangORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 (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 underwent novel multinuclear lithium magnetic resonance imaging (7Li-MRI) to determine the 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: Lithium-treated bipolar disorder and healthy controlgroups had higher mean white matter gFA than the bipolar disorder group treated with other medications (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. Limitations:Cross-sectional evaluation of a relatively small cohort. Conclusions: The higher gFA values observed in the lithium-treated bipolar disorder group suggests that long-term lithium is associated with greater white matter integrity. Our novel analysis supports this further, showing a positive association between white matter gFA and the spatial distribution of lithium.

Publication metadata

Author(s): Necus J, Sinha N, Smith FE, Thelwall PE, Flowers CJ, Taylor PN, Blamire AM, Cousins DA, Wang Y

Publication type: Article

Publication status: Published

Journal: Journal of Affective Disorders

Year: 2019

Volume: 253

Pages: 224-231

Print publication date: 15/06/2019

Online publication date: 18/04/2019

Acceptance date: 17/04/2019

Date deposited: 29/04/2019

ISSN (print): 0165-0327

ISSN (electronic): 1573-2517

Publisher: Elsevier


DOI: 10.1016/j.jad.2019.04.075


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Funder referenceFunder name
208940/Z/17/ZWellcome Trust
210109/Z/18/ZWellcome Trust
Reece Foundation Laboratories for Translational Systems Neuroscience