Background: Previous work has identified subtle differences in white matter structure between individuals with first-episode psychosis and chronic schizophrenia, and controls. One way of analysing white matter integrity is through the use of diffusion tensor imaging (DTI), which is able to characterise microstructural features of individual white matter structures, through the use of measures such as fractional anisotropy (FA).
Subjects: We compared the FA maps of 14 first-episode medication-free psychosis patients with 13 healthy matched controls. Subjects underwent scanning on a 3.0T GE system using sequences optimised for diffusion-weighted images in 28 diffusion directions with 5 b0 images. A subset of subjects had follow-up scans after three months’ treatment with aripiprazole and other antipsychotic medications.
Methods: All FA maps were registered to an FA template supplied by the FSL Software Package (FMRIB Analysis Group, Oxford, UK), to minimize distortions caused by registration. The FA template was registered to MNI 152, and then all individual FA maps were registered to MNI152 using the combination of the two registration transforms. The registration was using the IRTK method as part of the TBSS package which combines affine and non-linear registration, which has been demonstrated to maintain individual anatomical differences whilst maximising registration of common areas of white matter. A white matter mask of FA >0.2 was then applied to all images, and we then compared groups in a permutation-based nonparametric inference voxel- and cluster-wise analysis using a standard general linear model design with 5000 permutations, as used in the FSL package.
Results: Regions of difference were identified in the bifrontal white matter (orbitofrontal and medial frontal), left and right temporal regions, left and right parietal regions, and the right cerebellum. In all of these areas, patients showed a lower FA than controls. In no areas did controls show a lower FA than patients. Data will also be presented showing FA changes after three months’ continuous antipsychotic treatment.
Discussion: The white matter in a range of cortical regions show reductions in FA, suggesting widespread but subtle changes to the organization and/or integrity of white matter tracts in these regions in first-episode psychosis.
Acknowledgements: This study was supported by grants from Bristol Myers Squibb Australia, the Stanley Foundation.
