Introduction: Disruptions in white matter (WM) in schizophrenia have been reported in several diffusion tensor imaging (DTI) studies, such as altered fractional anisotropy (FA) in the corpus callosum or the anterior limb of internal capsule. These results suggested the brain dysconnectivity of patients with schizophrenia. However, previous studies provide heterogenous results due to relatively small and varying sample size between studies, imaging analysis protocols, scanner differences and the large variability in data acquisition.
Objective: To investigate the WM disruptions and their correlation with the symptom severity in schizophrenia patients using generalized TBSS analysis.
Methods: Diffusion MRI (dMRI) data of 190 patients with schizophrenia and 212 healthy controls from 4 different study sites were obtained. Harmonization of dMRI data was applied to adjust the possible inter-site differences. Generalized TBSS analysis, involving advanced normalization tools at a registration step, as well as original TBSS analysis were carried out. The voxel-wise and a region of interest (ROI)-based differences in WM parameters between patients and healthy controls were investigated. Correlation analysis was performed to examine the association between PANSS scores and WM parameters. Age and gender were included into all the analyses as covariates.
Results: Aberrant registration results of DTI images of several subjects were found in original TBSS. In Generalized TBSS analysis, the patients with schizophrenia showed widespread decreases in FA and axial diffusivity (AD) and increases in radial diffusivity (RD) in both voxel-wise and ROI-based analyses. Correlation between white matter parameters and the symptom severity in numerous white matter regions was also observed in this study. There were trending positive correlation between FA and PANSS scores, and trending negative correlation between PANSS scores and MD, AD, and RD respectively.
Conclusions: We could conclude that WM disruptions are diffusely distributed in the disease and both positive and negative symptoms of schizophrenia correlated with the brain dysconnectivity.