Cellular and extracellular white matter alterations indicate conversion to psychosis among individuals at clinical high-risk for psychosis

TY - JOUR

T1 - Cellular and extracellular white matter alterations indicate conversion to psychosis among individuals at clinical high-risk for psychosis

AU - Nägele, Felix L

AU - Pasternak, Ofer

AU - Bitzan, Lisa V

AU - Mußmann, Marius

AU - Rauh, Jonas

AU - Kubicki, Marek

AU - Leicht, Gregor

AU - Shenton, Martha E

AU - Lyall, Amanda E

AU - Mulert, Christoph

PY - 2021/3

Y1 - 2021/3

N2 - OBJECTIVES: It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP).METHODS: Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed.RESULTS: There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP.CONCLUSIONS: Our study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.

AB - OBJECTIVES: It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP).METHODS: Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed.RESULTS: There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP.CONCLUSIONS: Our study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.

U2 - 10.1080/15622975.2020.1775890

DO - 10.1080/15622975.2020.1775890

M3 - SCORING: Journal article

C2 - 32643526

VL - 22

SP - 214

EP - 227

JO - WORLD J BIOL PSYCHIA

JF - WORLD J BIOL PSYCHIA

SN - 1562-2975

IS - 3

ER -