Microstructural Alterations of the Corpus Callosum in Patients with First-Episode Schizophrenia Revealed by NODDI: Dissociation Between Neurite Density and Orientation Dispersion in the Splenium.

backgroundMicrostructural abnormalities of the corpus callosum (CC) are a consistent finding in schizophrenia, yet conventional diffusion tensor imaging (DTI) metrics provide limited biological specificity. Neurite orientation dispersion and density imaging (NODDI) can disentangle the neurite density index (NDI) and the orientation dispersion index (ODI), providing indirect, model-based markers of white matter microstructure in vivo.

methodsWe applied NODDI to diffusion-weighted MRI data in patients with first-episode schizophrenia (FES) and matched healthy controls (HCs). The CC was used as a mask and subdivided into the genu (GCC), body (BCC), and splenium (SCC). Group differences in z-scores of the NDI and ODI were assessed using voxel-wise statistics within the CC and region of interest (ROI) analyses in the GCC, BCC, and SCC, controlling for age and sex. Associations between NODDI metrics and clinical symptoms were examined using the Positive and Negative Syndrome Scale (PANSS).

resultsFES patients showed a significantly increased ODI in portions of the GCC, BCC, and SCC, as well as region-specific NDI alterations, with decreased NDI in parts of the SCC and increased NDI in sub-regions of the GCC/BCC (voxel-wise

conclusionsOur findings suggest that, in the SCC, negative symptoms in schizophrenia are linked to altered neurite orientation dispersion under conditions of reduced neurite density. The dissociation between group-level NDI and ODI effects and their distinct relationship with psychopathology highlights the value of composite microstructural indices (e.g., residual