Recent findings on the role of white matter pathology in bipolar disorder

Patients with bipolar disorder (BD) experience difficulties in information processing and in the cognitive control of emotions. Mood-congruent biases, which parallel illness episodes, find a neural correlate in abnormal reactivity to stimuli in specific brain regions, and in disrupted functional connectivity among brain areas pertaining to corticolimbic circuitries. It is suggested that a reduced integrity of white matter tracts could underpin dysfunctions in networks implicated in the generation and control of affect. Recent studies using diffusion tensor imaging techniques found that (1) independent of drug treatment, patients with BD show widespread signs of disrupted white matter microstructure, suggesting significant demyelination/dysmyelination without axonal loss, and (2) effective long-term treatment with lithium is associated with increased axial connectivity, proportional to the duration of treatment. These findings suggest that changes of white matter microstructure in specific brain networks could parallel disrupted neural connectivity during illness episodes in BD and that these changes might play a major role in the mechanistic explanation of the biological underpinnings of BD psychopathology.