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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\u2009\u00b1\u20096) versus 49 healthy controls (HC, mean age 25\u2009\u00b1\u20096). 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.<\/jats:p>","DOI":"10.1038\/s41398-026-04072-9","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:59:01Z","timestamp":1780408741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myo-inositol concentration in the medial prefrontal cortex is associated with changes in brain white matter microstructure in early psychosis"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-6882","authenticated-orcid":false,"given":"Tommaso","family":"Pavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0234-6864","authenticated-orcid":false,"given":"Qiaochu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Alem\u00e1n-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-5381","authenticated-orcid":false,"given":"Raoul","family":"Jenni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Cleusix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8621-2885","authenticated-orcid":false,"given":"Luis","family":"Alameda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1968-1646","authenticated-orcid":false,"given":"Kim","family":"Q. 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