Bipolar disorder (BD) is strongly associated with white matter abnormalities. Postmortem studies have revealed a reduction in glial cells in the subgenual prefrontal cortex (1) and there is evidence from T2-weighted magnetic resonance imaging (MRI) that patients with BD have an increase in white matter hyperintensities compared to healthy controls (2, 3). T1-weighted MRI has also revealed white matter reductions using both region of interest (ROI) (4, 5) and voxel-based morphometry (VBM) approaches (6).
Conventional T1-weighted MRI is, however, limited in its ability to identify abnormalities of white matter, since the signal is largely dependent upon water content and is potentially confounded by non-neuronal tissue components. Diffusion tensor imaging (DTI) is a more recent technique that measures the diffusivity of water molecules within tissues in vivo. Yet there have been few DTI studies in BD and all of these have had relatively small sample sizes. Their findings have included reduced prefrontal (4, 5, 7) and posterior internal capsule (7) white matter integrity, and altered integrity in orbital frontal white matter (8). Despite this paucity of BD-related research, the available evidence suggests altered prefrontal-subcortical connectivity, in line with a growing body of functional imaging literature implicating dysfunction in the frontostriatal and frontothalamic circuits in the development of BD. These findings are supported by an expanding body of work including abnormalities of myelin-associated gene expression (9) and studies using conventional T1-weighted MRI (10, 11).
Schizophrenia and BD show some overlap in relation to shared genetic aetiology (12), clinical symptoms, pharmacological interventions, and course (13). The most common positive DTI findings in schizophrenia have included decreased fractional anisotropy (FA) in temporal and prefrontal regions (14–16) and their connections: the uncinate fasciculus (17, 18), internal capsule (19), and genu of the corpus callosum (20). Indirect comparison of the literature in these disorders using T1-weighted MRI and DTI therefore suggests that deficits in the internal capsule may be common to both disorders, whereas uncinate deficits have been found only in schizophrenia. However, conclusions about whether or not these represent common or unique white matter abnormalities are hampered by the lack of any direct DTI comparison, where both disorders have been examined in the same study. Our study sought to address this issue.
Despite its increasing use in clinical populations, there remains a general lack of agreement about how DTI data are best analysed. We and others have previously used an adaptation of VBM techniques to compare FA at specific points on prespecified tracts in schizophrenia (18). We therefore wished to apply the same methodology in this study to provide a direct comparison with our previous findings. The VBM approach is, however, potentially biased by registration differences between groups. We therefore conducted a complimentary automated ROI study of FA between the three groups in which the specific ROIs were hand traced, both to provide an additional test of internal replication and to deal with the potential issue of misregistration.