Myo-Inositol Concentration in the Medial Prefrontal Cortex is Associated with Changes in Brain White Matter Microstructure in Early Psychosis

Recent research highlights the critical role of white matter (WM) alterations in psychosis and schizophrenia (SZ), reporting volumetric and structural brain changes in affected individuals. In this study, we explored the role of astroglia in SZ, which is believed to play a role in white matter integrity. We investigated for the first time the associations between advanced diffusion Magnetic Resonance Imaging (dMRI) measures of WM microstructure and Magnetic Resonance Spectroscopy (MRS)-derived glial markers in 30 subjects with early psychosis (EP, mean age 24 ± 6) versus 49 healthy controls (HC, mean age 25 ± 6). We focused on two metabolites involved in glia: myo-Inositol (myo-Ins) and total Choline (tCho), measured in the medial prefrontal cortex (mPFC), relating them to quantitative dMRI metrics derived from Diffusion Kurtosis Imaging (DKI) and WM Tract Integrity-Watson (WMTI-W) biophysical model, including mean diffusivity and kurtosis, axonal water fraction and extra-axonal diffusivities in the whole white matter. Our findings reveal a difference between EP and HC in WM diffusivities, specifically in the extra-axonal parallel direction, but not in MRS metabolites. However, we found that the mPFC myo-Ins concentrations in EP are exclusively and strongly associated with proximal WM microstructure features, in the form of a positive correlation with axonal water fraction, a proxy for axonal density, and a negative correlation with extra-axonal parallel diffusivity, suggesting the white matter alterations could be linked to astrocytic changes in early psychosis.