Disruption of white matter integrity in bipolar depression as a possible structural marker of illness

Background: Diffusion tensor imaging allows the study of integrity of white matter (WM) tracts. Literature suggests that WM integrity could be altered in bipolar disorder. Heterogeneity of brain imaging methods, the studied samples, and drug treatments make localization, nature, and severity of the WM abnormalities unclear. Methods: We applied tract-based spatial statistics of diffusion tensor imaging measures to compare fractional anisotropy (FA), mean, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by a major depressive episode without psychotic features with a diagnosis of bipolar disorder type I and 21 unrelated healthy volunteers from the general population. Results: Compared with control subjects, patients showed lower FA in the genu of the corpus callosum and in anterior and right superior-posterior corona radiata and higher values of radial diffusivity in WM tracts of splenium, genu and body of corpus callosum, right mid-dorsal part of the cingulum bundle, left anterior and bilateral superior and posterior corona radiata, bilateral superior longitudinal fasciculus, and right posterior thalamic radiation. Patients had no brain areas with higher FA or lower diffusivity values than control subjects. Conclusions: Reduced FA with increased mean and radial diffusivity suggests significant demyelination and/or dysmyelination without axonal loss. Comparing our findings with other observations in homogeneous samples of euthymic and manic patients, it can be hypothesized that changes in measures of WM integrity might parallel illness phases of bipolar illness.