Fibre tract analysis using diffusion tensor imaging reveals aberrant connectivity in a rat model of depression

Objectives: Abnormal brain connectivity has been described in depressive disorder. However, these studies are correlational or cross-sectional and their design does not examine causal relationships. We aimed to investigate structural connectivity in a genetic rat model of depression. Methods: Using diffusion tensor imaging (DTI), we reconstructed white matter tracts and analysed fractional anisotropy (FA) and diffusivity indices (mean, axial and radial) to investigate structural connectivity in fibre tracts implicated in major depression: the corpus callosum, fornix, cingulum and anterior commissures. Results: Tractography-based analysis revealed that, compared to Wistar control rats, the Wistar–Kyoto strain (WKY) rat model of depression exhibited decreased connectivity, manifested by decreased FA in the corpus callosum, right and left anterior commissures. A statistical trend of decreased FA was observed in both the right and left cingulum. Increased diffusivity (mean diffusion) was detected in both the corpus callosum and the fornix of WKY rats compared to controls. Voxel-based analysis confirmed differences between WKY and controls in the regions investigated. Conclusions: Decreased connectivity in a genetic rat model of depression corroborates the findings in patients suffering from major depression suggesting that the vulnerability for developing depression is mainly polygenic and less likely to be due to childhood adversity per se.