Parsing heterogeneity in global and local white matter integrity at different stages across the psychosis continuum

Abstract Psychosis progresses along a continuum. While clinical heterogeneity is evident across the continuum, it remains unknown whether this is also reflected in white matter (WM) heterogeneity and whether parsing WM heterogeneity may reveal subgroups with more pronounced clinical features. This analysis included 212 participants consisting of healthy controls (HC, n=59), individuals with high schizotypy (SPT, n=27), at-risk mental state (ARMS, n=35), and patients with first episode psychosis (FEP, n=50) and schizophrenia (SZ, n=41). Fractional anisotropy (FA), mean diffusivity (MD) and fiber density (FD) were derived from diffusion tensor imaging (DTI) and the Person-Based-Similarity Index (PBSI) and Coefficient of Variation Ratio (CVR) were computed to assess global and local heterogeneity. ANCOVAs were performed to determine whether people with deviating PBSIs exhibit more pronounced clinical features. Global heterogeneity for all DTI parameters significantly differed across groups, with greatest heterogeneity in SZ and SPT. Results further indicate that FA deviators exhibit lower global functioning and higher negative symptoms. Local FA heterogeneity was greater in FEP relative to ARMS and HC in almost all WM tracts, while SZ patients specifically showed greater heterogeneity in the right thalamic radiation and the left uncinate compared to HCs. Group differences in WM heterogeneity might be indicative of symptom specificity and duration. Future large-scale studies are warranted to test the robustness of DTI subtypes and their clinical relevance.