Disentangling white matter correlates of symptom severity and general impairment in early psychosis

N Penzel; KIK Cho; J Seitz-Holland; A Ruef; G Cabras; PC Klein; LA Antonucci; D Dwyer; LT Betz; S Cetin Karayumak; S Haas; F Zhang; MF Urquijo Castro; GR Jacobs; U Ettinger; P Falkai; G Pergola; R Upthegrove; S Borgwardt; P Brambilla; R Lencer; E Meisenzahl; F Schultze-Lutter; M Rosen; T Lichtenstein; L Kambeitz-Ilankovic; S Ruhrmann; RRK Salokangas; SJ Wood; C Pantelis; A Bertolino; ME Shenton; N Koutsouleris; O Pasternak; J Kambeitz

Journal article

Disentangling white matter correlates of symptom severity and general impairment in early psychosis

N Penzel, KIK Cho, J Seitz-Holland, A Ruef, G Cabras, PC Klein, LA Antonucci, D Dwyer, LT Betz, S Cetin Karayumak, S Haas, F Zhang, MF Urquijo Castro, GR Jacobs, U Ettinger, P Falkai, G Pergola, R Upthegrove, S Borgwardt, P Brambilla Show all

Molecular Psychiatry | Published : 2026

DOI: 10.1038/s41380-026-03832-9

Open access

Abstract

White matter (WM) alterations are well documented in individuals at clinical high-risk for psychosis (CHR-P) and with recent-onset psychosis (ROP), yet it remains unclear whether they reflect vulnerability, psychosis-related symptom severity, or general impairments shared with other disorders such as depression. To disentangle these correlates, we analyzed diffusion MRI data from 882 individuals (457 females) of the multisite Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, including 183 CHR-P, 206 ROP, 298 healthy controls, and 195 individuals with depression who were assessed as a clinical comparison group of observed associations. Fractional anisotropy (FA) was..

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