White matter differences in euthymic bipolar I disorder: A combined magnetic resonance imaging and diffusion tensor imaging voxel-based study

Objectives: A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients. Methods: Structural magnetic resonance imaging (sMRI) was obtained for 60 patients with prospectively confirmed euthymic bipolar I disorder and 60 individually age- and gender-matched healthy volunteers. High angular resolution diffusion tensor imaging (DTI) scans were obtained for a subset of this sample comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed. Results: Bipolar disorder patients displayed global reductions in white matter volume and fractional anisotropy reductions in the corpus callosum, posterior cingulum, and prefrontal white matter compared with controls. There were corresponding increases in radial diffusivity in the callosal splenium in patients compared with controls. No significant group differences were detected in grey matter. In patients, lithium was associated with a bilateral increase in grey matter volume in the temporal lobes, but not with any DTI parameter. Conclusions: Euthymic bipolar I disorder is characterized by both diffuse global white matter deficits and potential regional disorganization in interhemispheric and longitudinal tracts, while grey matter appears to be preserved.