White matter integrity in bipolar disorder investigated with diffusion tensor magnetic resonance imaging and fractal geometry

Background: Growing evidence suggests the presence of white matter (WM) alterations in bipolar disorder (BD). In this study we aimed to investigate the state of WM structures, in terms of tissue integrity and morphological complexity, in BD patients compared to healthy controls (HC), in an attempt to better elucidate the microstructural changes associated with BD.Methods: We collected a dataset of 399 Diffusion Tensor Magnetic Resonance Imaging (167 BD and 232 healthy controls) images, acquired at five different sites, which was processed with Tract-Based Spatial Statistics (TBSS) and fractal analysis.Results: The TBSS analysis demonstrated significantly lower FA values in the BD group. Diffusion abnormalities were primarily located in the temporo-parietal network. The Fractal Dimension (FD) analysis did not reveal consistent significant differences in the morphological complexity of WM structures between the groups. When the FD values of patients were considered individually, it is possible to notice some localized significant deviations from the healthy population. Limitations: DTI sequences have not been harmonized before acquisition, samples' sizes are heterogeneous. Conclusions: This study, by applying both TBSS and FD analyses, allows to evaluate diffusion and structural alterations of WM at the same time. The evaluation of WM integrity from these two different perspectives could be useful to better understand the pathophysiological and morphological changes underpinning bipolar disorder.