S139. PROGRESSIVE DETERIORATION OF WHITE MATTER TRACTS IN SCHIZOPHRENIA: A DIFFUSION MRI STUDY ON A LARGE SINGLE COHORT USING NORMATIVE MODELS

Abstract Background Current diffusion MRI studies of schizophrenia are limited by methodology and sample size. With normative models and the largest single-site cohort, we aimed to delineate a comprehensive profile of tract alteration in unaffected siblings, first-episode schizophrenia (FES), and chronic schizophrenia. Methods A total of 277 patients with schizophrenia, 81 unaffected siblings, and 1023 healthy people underwent diffusion-weighted imaging on the same 3T scanner. Generalized fractional anisotropy (GFA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were sampled along 45 major neural tracts. A normative model was built from the images of 1023 healthy people; Z scores represented the normalized deviation of the index value from that of the age- and sex-matched healthy population. Results Widespread involvement of neural tracts was found in patients with FES, and the tracts connecting the prefrontal lobe were the most severely affected. In patients with chronic schizophrenia, virtually all neural tracts were altered, with the tracts connecting the sensorimotor cortex the least affected. A significant negative correlation was observed between GFA alterations and the duration of illness. In unaffected siblings, scattered tracts were involved in GFA, but not in MD or RD. Discussion The study revealed widespread white matter involvement in the early stages of schizophrenia. The alteration continues to progress from the neural tracts connecting the prefrontal lobe to the entire brain. Compared to a large sample of normal controls, the attenuated peak and rapid decline of white matter GFA across the lifespan suggest that schizophrenia is associated with neurodevelopmental and neurodegenerative abnormalities of white matter.