White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study

Objectives: In bipolar disorder (BD), dysregulation of mood may result from white matter abnormalities that disrupt fronto-subcortical circuits. In this study, we explore such abnormalities using diffusion tensor imaging (DTI), an imaging technique capable of detecting subtle changes not visible with conventional magnetic resonance imaging (MRI), and voxel-based analysis. Methods: Thirty-six patients with BD, all but two receiving antidepressants or mood stabilizers, and 28 healthy controls matched for age and gender were studied. Diffusion-weighted echoplanar images (DW-EPI) were obtained using a 1.5T scanner. Voxel-based analysis was performed using SPM 2. Differences between the groups in mean diffusivity and fractional anisotropy (FA) were explored. Results: In the patient group, mean diffusivity was increased in the right posterior frontal and bilateral prefrontal white matter, while FA was increased in the inferior, middle temporal and middle occipital regions. The areas of increased mean diffusivity overlapped with those previously found to be abnormal using volumetric MRI and magnetization transfer imaging (MTI) in the same group of patients. Conclusions: White matter abnormalities, predominantly in the fronto-temporal regions, can be detected in patients with BD using DTI. The neuropathology of these abnormalities is uncertain, but neuronal and axonal loss, myelin abnormalities and alterations in axonal packing density are likely to be relevant. The neuroprotective effects of some antidepressants and mood stabilizers make it unlikely that medication effects could explain the abnormalities described here, although minor effects cannot be excluded.