Along-tract white matter abnormalities and their clinical associations in recent-onset and chronic schizophrenia

Structural impairments in white matter tracts are well-documented in schizophrenia, though their clinical implications remain limited. Most previous studies using diffusion-weighted magnetic resonance imaging (dMRI) and tractography relied on averaged diffusion indices, potentially obscuring localized changes in white matter tracts. Tractometry enables the investigation of localized changes at specific points along white matter tracts. We used dMRI and centerline tractometry to examine along-tract white matter abnormalities in 55 patients with recent-onset schizophrenia, 69 with chronic schizophrenia, and 77 healthy controls. Fractional anisotropy (FA) and peak length were measured at individual points along tract trajectories. Group differences in diffusion indices and their associations with clinical variables, including the Positive and Negative Syndrome Scale (PANSS), were analyzed using linear mixed models and Spearman's rho. In recent-onset schizophrenia, reduced FA was observed in the genu and splenium of the corpus callosum, along with deviations in peak length across multiple white matter tracts. The peak length of association tracts showed a negative correlation with antipsychotic dose. In chronic schizophrenia, widespread reductions in FA and deviations in peak length were identified across various white matter tracts. Decreased FA in commissural tracts was negatively associated with the PANSS negative score, antipsychotic dose, and illness duration. This study identified along-tract white matter abnormalities in recent-onset and chronic schizophrenia and revealed their associations with clinical symptoms. Localized measurements along tract trajectories enhance the detection of clinically relevant abnormalities compared to traditional methods relying on averaged diffusion indices.