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

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 ( 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 underwent novel multinuclear lithium magnetic resonance imaging ( 7 Li-MRI) to determine the relative lithium concentration across the brain. The relationship between 7 Li-MRI signal intensity and gFA was investigated at the resolution of the 7 Li-MRI sequence in native space. Results Lithium-treated bipolar disorder and healthy control groups had higher mean white matter gFA than the bipolar disorder group treated with other medications ( t  = 2.5, p t  = 2.7, p 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 7 Li-MRI signal in predicting the gFA ( p 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.