A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry

Bipolar disorder (BP) traditionally has been considered as a recurrent illness with full recovery between episodes, and the absence of neuropathological abnormalities has usually been taken for granted. In recent times, the realization that, for many BP carries a poor prognosis, that cognitive deficits are often persistent and that structural brain abnormalities are detectable with modern imaging techniques has spurred the search for its neuropathological substrate. The shortcomings of post-mortem studies make the use of imaging techniques sensitive to neuropathological changes compelling. We report here the first study of BP patients using two such techniques in conjunction: magnetization transfer imaging (MTI) and voxel-based morphometry (VBM). Thirty-nine patients with BP (13 males and 26 females; 28 with BPI and 11 with BPII) and 35 healthy controls were investigated. Both high-resolution volumetric T1-weighted images and MT images were acquired from all subjects. Images were processed using a voxel-by-voxel analysis in statistical parametric mapping 2 (SPM2). The magnetization transfer ratio MTR, an index indicative of loss of macromolecular density, was reduced in the right subgenual anterior cingulate and adjacent white matter in bipolar patients compared with controls. VBM did not reveal significant volumetric differences between BP patients and controls in grey and white matter, but white matter density was significantly reduced bilaterally in prefrontal areas encompassing fronto-striatal connections. Our findings suggest that subtle abnormalities are present in the anterior cingulate and subgyral white matter in patients with BP in the absence of significant volumetric changes. These findings are in keeping with those of previously reported neuropathological studies and illustrate important similarities (involvement of the anterior cingulate) and differences (lack of widespread cortical abnormalities in BP) with our previous studies in schizophrenic patients using the same methodology.