White matter microstructural abnormalities in bipolar disorder: A whole brain diffusion tensor imaging study

Abstract

Background: Bipolar disorder (BD) is a chronic mental illness characterized by severe disruptions in mood and cognition. Diffusion tensor imaging (DTI) studies suggest that white matter (WM) tract abnormalities may contribute to the clinical hallmarks of the disorder. Using DTI and whole brain voxel-based analysis, we mapped the profile of WM anomalies in BD. All patients in our sample were euthymic and lithium free when scanned.

Methods: Diffusion-weighted and T1-weighted structural brain images were acquired from 23 lithium-free euthymic subjects with bipolar I disorder and 19 age- and sex-matched healthy control subjects on a 1.5 T MRI scanner. Scans were processed to provide measures of fractional anisotropy (FA) and mean and radial diffusivity (MD and RD) at each WM voxel, and processed scans were nonlinearly aligned to a customized brain imaging template for statistical group comparisons.

Results: Relative to controls, the bipolar group showed widespread regions of lower FA, including the corpus callosum, cortical and thalamic association fibers. MD and RD were abnormally elevated in patients in many of these same regions.

Conclusions: Our findings agree with prior reports of WM abnormalities in the corpus callosum and further link a bipolar diagnosis with structural abnormalities of the tapetum, fornix and stria terminalis. Future studies assessing the diagnostic specificity and prognostic implications of these abnormalities would be of interest.

Keywords: Bipolar disorder; Brain mapping; DTI; Fractional anisotropy; Neuroimaging; White matter.

Fig. 1

Fractional anisotropy differences in bipolar patients vs. controls. a. White matter regions where fractional anisotropy (FA) was significantly lower in bipolar patients compared to healthy controls. p-values have been corrected with searchlight FDR. b. Regression coefficients in white matter regions where voxels differed significantly between groups. Units are in FA unit difference between groups. PTR—posterior thalamic radiation; PCR—posterior corona radiata, SCR—superior corona radiata; SLF—superior longitudinal fasciculus; ILF—inferior longitudinal fasciculus; IFOF—inferior fronto-occipital fasciculus; CC—corpus callosum; L—left; R—right.

Fig. 2

Mean diffusivity differences in bipolar patients vs. controls. a. White matter regions where mean diffusivity (MD) was significantly higher in bipolar patients compared to healthy controls. p-values have been corrected with searchlight FDR. b. Regression coefficients in white matter regions where voxels differed significantly between groups. Units are in MD unit difference between groups. ALIC—anterior limb of internal capsule; PLIC—posterior limb of internal capsule; RLIC—retrolenticular limb of internal capsule; PTR—posterior thalamic radiation; SLF—superior longitudinal fasciculus; ILF—inferior longitudinal fasciculus; IFOF—inferior fronto-occipital fasciculus; CC—corpus callosum; ST—stria terminalis; L—left; R—right; *—DTI resolution precludes resolving with anatomical certainty.

Fig. 3

Radial diffusivity differences in bipolar patients vs. controls. a. White matter regions where radial diffusivity (RD) was significantly higher in bipolar patients compared to healthy controls. p-values have been corrected with searchlight FDR. b. Regression coefficients in white matter regions where voxels differed significantly between groups. Units are in RD unit difference between groups. ALIC—anterior limb of internal capsule; PLIC—posterior limb of internal capsule; RLIC—retrolenticular limb of internal capsule; PTR—posterior thalamic radiation; PCR—posterior corona radiata, SCR—superior corona radiata; SLF—superior longitudinal fasciculus; ILF—inferior longitudinal fasciculus; IFOF—inferior fronto-occipital fasciculus; SFOF—superior fronto-occipital fasciculus; CC—corpus callosum; ST—stria terminalis; L—left; R—right; *—DTI resolution precludes resolving with anatomical certainty.

Fig. 4

Mean FA values in the corpus callosum, for each subject, are plotted by diagnostic group. Control FA values are shown in blue and bipolar FA values are shown in red. Values for subjects who had a history of drug abuse or dependence are outlined in purple.