White Matter Microstructure Alterations in Early Psychosis and Schizophrenia

Abstract

Background and Hypothesis: Studies on schizophrenia feature diffusion magnetic resonance imaging (dMRI) to investigate white matter (WM) anomalies. The heterogeneity in the possible interpretations of these metrics highlights the importance of increasing their specificity. Here, we characterize WM pathology in early psychosis (EP) and schizophrenia (SZ) with increased specificity using advanced dMRI metrics: Diffusion Kurtosis Imaging and White Matter Track Integrity - Watson (WMTI-W) biophysical model. This enables us to better characterize WM abnormalities and relate them to symptomatology. Study Design: dMRI-derived microstructure features were extracted from all of WM and from individual tracts in 275 individuals. 93 patients with EP and 47 with SZ were compared respectively to 135 age-range matched healthy controls (HC). The relationships between the dMRI metrics in WM and various clinical scales were investigated in each patient group. Study Results: WM diffusivities were higher, while kurtosis was lower in EP and SZ vs HC. Differences were more pronounced in EP than SZ. WMTI-W model parameters suggest alterations to the extra-axonal compartment in EP and SZ, consistent with abnormal myelin integrity and WM deterioration. Patient groups showed clustered but non-significant correlations between dMRI metrics and psychotic symptoms. Depressive dimensions were significantly associated with decreased diffusivities in WM, while manic scales correlated with increased diffusivities and reduced kurtosis. Conclusions: dMRI patterns in EP and SZ highly suggest WM deterioration in comparison to HC. DMRI changes better align with affective dimensions, while the relationship with psychotic symptoms may be confounded by competing pathological effects on the microstructure and disease heterogeneity.