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 naive 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 naive 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.
