Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra-high risk for psychosis

TY - JOUR

T1 - Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra-high risk for psychosis

AU - Kristensen, Tina D.

AU - Mandl, René C W

AU - Raghava, Jayachandra M

AU - Jessen, Kasper

AU - Jepsen, Jens Richardt M.

AU - Fagerlund, Birgitte

AU - Glenthøj, Louise B

AU - Wenneberg, Christina

AU - Krakauer, Kristine

AU - Pantelis, Christos

AU - Nordentoft, Merete

AU - Glenthøj, Birte Y.

AU - Ebdrup, Bjørn H.

N1 - Funding information: Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Grant/Award Numbers: R13‐A1349, R25‐A2701, R155‐2013‐16337; Mental Health Services of the Capital Region of Denmark; Research Fund of the Capital Region Denmark; the Lundbeck Foundation; TrygFonden, Grant/Award Number: 108119

PY - 2019/12/15

Y1 - 2019/12/15

N2 - In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra-high risk for psychosis. One hundred and sixteen individuals at ultra-high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion-weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract-based spatial statistics. Group differences in cognitive functions, voxel-wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra-high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra-high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra-high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction-effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.

AB - In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra-high risk for psychosis. One hundred and sixteen individuals at ultra-high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion-weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract-based spatial statistics. Group differences in cognitive functions, voxel-wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra-high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra-high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra-high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction-effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.

U2 - 10.1002/hbm.24765

DO - 10.1002/hbm.24765

M3 - Journal article

C2 - 31430023

SN - 1065-9471

VL - 40

SP - 5185

EP - 5201

JO - Human Brain Mapping

JF - Human Brain Mapping

IS - 18

ER -