White matter microstructure alterations in early psychosis and schizophrenia

Studies on schizophrenia feature diffusion magnetic resonance imaging (dMRI) to investigate white matter (WM) anomalies. The heterogeneity in the possible interpretations of typical Diffusion Tensor Imaging (DTI) 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: Diffusion Kurtosis Imaging and the biophysical model White Matter Tract Integrity - Watson (WMTI-W). This enables us to better characterize WM abnormalities, while preserving good sensitivity to group differences, and relate them to the current literature (ENIGMA-schizophrenia), patient's clinical characteristics and symptomatology. dMRI-derived microstructure features were extracted from all of WM and from individual regions of interest in 275 individuals. 93 subjects diagnosed with EP and 47 with SZ were compared respectively to 135 age-range matched healthy controls (HC). WM DTI diffusivities were higher, while kurtosis was lower in EP vs HC and in SZ vs HC. Differences were more widespread in EP than SZ. The regional alterations found in our cohort matched the DTI patterns found in ENIGMA-schizophrenia. WMTI-W model parameters indicate that the WM alterations in patients come primarily from the extra-axonal compartment, consistent with abnormal myelin integrity in the disease pathology. The direct link between WM alterations and symptomatology is, however, limited.