Longitudinal White Matter Microstructure and Transition to Psychosis in Individuals at Clinical High Risk
- 1University of Oxford
Abstract
Altered white matter microstructure, commonly indexed by fractional anisotropy (FA), has been reported in individuals at clinical high-risk of psychosis (CHR-P) across multiple white matter tracts. However, the relationship between these alterations and later transition to psychosis remains unclear. To address this gap, we investigated whether baseline and longitudinally updated FA measurements were associated with risk of transition to psychosis in a large cohort of individuals at CHR-P. We analysed diffusion tensor imaging data from N = 205 participants at CHR-P, 23 of whom developed psychosis within 3 years of follow-up. Data were collected at baseline, 6 months, and 12 months. Associations between global and tract-specific FA and transition risk were examined using Cox proportional hazards models of baseline data and longitudinally updated data. Point estimates were directionally consistent, with hazard ratios <1 for FA across all white matter tracts in both baseline and longitudinal models. Associations reached nominal significance in the hippocampal cingulum, anterior thalamic radiation, and forceps minor, but none of these remained significant after correcting for multiple comparisons (pcorr > .05). The directionally consistent estimates are compatible with small, distributed effects across multiple white matter pathways being associated with transition to psychosis, although this requires replication. Longitudinally updated FA measurements did not yield stronger associations than were available from baseline imaging data alone. Studies at an even larger scale are needed to establish whether these associations are robust and clinically meaningful.
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BibTeX
@misc{bolte2026longitudinal,
title = {{Longitudinal White Matter Microstructure and Transition to Psychosis in Individuals at Clinical High Risk}},
author = {L. Bolte and G. Gifford and M. Serpa and M. Cottaar and P. Dazzan and P. Fusar-Poli and S. Tognin and A. Cullen and M. Kempton and M. Slot and H. van Hell and A. Maat and L. de Haan and B. Crespo Facorro and B. Glenthoj and S. Lawrie and T. Amelsvoort and C. Arango and I. Falkenberg and B. Nelson and S. Galderisi and R. Bressan and J. S. Kwon and K. I. K. Cho and M. Weiser and R. Mizrahi and G. Sachs and M. Kirschner and M. Taquet and PSYSCAN Consortium and R. Kahn and D. Oliver and P. McGuire},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754817},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754817v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Longitudinal White Matter Microstructure and Transition to Psychosis in Individuals at Clinical High Risk
AU - L. Bolte
AU - G. Gifford
AU - M. Serpa
AU - M. Cottaar
AU - P. Dazzan
AU - P. Fusar-Poli
AU - S. Tognin
AU - A. Cullen
AU - M. Kempton
AU - M. Slot
AU - H. van Hell
AU - A. Maat
AU - L. de Haan
AU - B. Crespo Facorro
AU - B. Glenthoj
AU - S. Lawrie
AU - T. Amelsvoort
AU - C. Arango
AU - I. Falkenberg
AU - B. Nelson
AU - S. Galderisi
AU - R. Bressan
AU - J. S. Kwon
AU - K. I. K. Cho
AU - M. Weiser
AU - R. Mizrahi
AU - G. Sachs
AU - M. Kirschner
AU - M. Taquet
AU - PSYSCAN Consortium
AU - R. Kahn
AU - D. Oliver
AU - P. McGuire
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754817
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754817v1
AB - Altered white matter microstructure, commonly indexed by fractional anisotropy (FA), has been reported in individuals at clinical high-risk of psychosis (CHR-P) across multiple white matter tracts. However, the relationship between these alterations and later transition to psychosis remains unclear. To address this gap, we investigated whether baseline and longitudinally updated FA measurements were associated with risk of transition to psychosis in a large cohort of individuals at CHR-P. We analysed diffusion tensor imaging data from N = 205 participants at CHR-P, 23 of whom developed psychosis within 3 years of follow-up. Data were collected at baseline, 6 months, and 12 months. Associations between global and tract-specific FA and transition risk were examined using Cox proportional hazards models of baseline data and longitudinally updated data. Point estimates were directionally consistent, with hazard ratios <1 for FA across all white matter tracts in both baseline and longitudinal models. Associations reached nominal significance in the hippocampal cingulum, anterior thalamic radiation, and forceps minor, but none of these remained significant after correcting for multiple comparisons (pcorr > .05). The directionally consistent estimates are compatible with small, distributed effects across multiple white matter pathways being associated with transition to psychosis, although this requires replication. Longitudinally updated FA measurements did not yield stronger associations than were available from baseline imaging data alone. Studies at an even larger scale are needed to establish whether these associations are robust and clinically meaningful.
ER -