Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background: Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method: Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results: Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations: Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions: There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.