Abstract
BackgroundLithium 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. MethodsEuthymic 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. ResultsLithium-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 < 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. LimitationsCross-sectional evaluation of a relatively small cohort. ConclusionsThe 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.
Highlights
Bipolar disorder is a major mental illness affecting 1% of the world's population
One BDL subject was excluded from the 7LiMRI analysis because their lithium imaging data was acquired during the 7Li-magnetic resonance imaging (MRI) sequence development phase and the acquisition protocol was inconsistent with the other subjects in the study
Post-hoc testing revealed that the HC group remained in education for longer than the BDL group (t = 2.59; p = 0.03) and the BDC group (t = 2.95; p = 0.01), but the bipolar disorder groups did not differ in years of education (t = 0.12; p = 0.9)
Summary
Bipolar disorder is a major mental illness affecting 1% of the world's population. numerous treatments are available, lithium retains a key position in major treatment guidelines, notably for the prevention of manic episodes (Severus et al, 2014). Cross-sectional structural magnetic resonance imaging (MRI) studies have revealed that treatment with lithium is associated with increased grey matter volume and cortical thickness (Hafeman et al, 2012; Hibar et al, 2018), and longitudinal studies have reported progressive increases in measures of grey matter volume following lithium initiation (Lyoo et al, 2010). These studies have generally shown that the effects of lithium on MRI estimates of grey matter volume are not uniform across the brain, and may localise to candidate regions such as the hippocampus, amygdala, anterior cingulate and prefrontal cortex (Zung et al, 2016; Hibar et al, 2018; Hibar et al, 2016; Monkul et al, 2007). Our novel analysis supports this further, showing a positive association between white matter gFA and the spatial distribution of lithium
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