Patterns of white matter microstructure in individuals at ultra-high-risk for psychosis: associations to level of functioning and clinical symptoms

TY - JOUR

T1 - Patterns of white matter microstructure in individuals at ultra-high-risk for psychosis

T2 - associations to level of functioning and clinical symptoms

AU - Krakauer, K

AU - Ebdrup, B H

AU - Glenthøj, B Y

AU - Raghava, J M

AU - Nordholm, D

AU - Randers, L

AU - Rostrup, E

AU - Nordentoft, M

PY - 2017/11/1

Y1 - 2017/11/1

N2 - BACKGROUND: Individuals at ultra-high-risk (UHR) for psychosis present with emerging symptoms and decline in functioning. Previous univariate analyses have indicated widespread white matter (WM) aberrations in multiple brain regions in UHR individuals and patients with schizophrenia. Using multivariate statistics, we investigated whole brain WM microstructure and associations between WM, clinical symptoms, and level of functioning in UHR individuals.METHODS: Forty-five UHR individuals and 45 matched healthy controls (HCs) underwent magnetic resonance diffusion tensor imaging (DTI) at 3 Tesla. UHR individuals were assessed with the Comprehensive Assessment of At-Risk Mental States, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Partial least-squares correlation analysis (PLSC) was used as statistical method.RESULTS: PLSC group comparisons revealed one significant latent variable (LV) accounting for 52% of the cross-block covariance. This LV indicated a pattern of lower fractional anisotropy (FA), axial diffusivity (AD), and mode of anisotropy (MO) concomitant with higher radial diffusivity (RD) in widespread brain regions in UHR individuals compared with HCs. Within UHR individuals, PLSC revealed five significant LVs associated with symptoms and level of functioning. The first LV accounted for 31% of the cross-block covariance and indicated a pattern where higher symptom score and lower level of functioning correlated to lower FA, AD, MO, and higher RD.CONCLUSIONS: UHR individuals demonstrate complex brain patterns of WM abnormalities. Despite the subtle psychopathology of UHR individuals, aberrations in WM appear associated with positive and negative symptoms as well as level of functioning.

AB - BACKGROUND: Individuals at ultra-high-risk (UHR) for psychosis present with emerging symptoms and decline in functioning. Previous univariate analyses have indicated widespread white matter (WM) aberrations in multiple brain regions in UHR individuals and patients with schizophrenia. Using multivariate statistics, we investigated whole brain WM microstructure and associations between WM, clinical symptoms, and level of functioning in UHR individuals.METHODS: Forty-five UHR individuals and 45 matched healthy controls (HCs) underwent magnetic resonance diffusion tensor imaging (DTI) at 3 Tesla. UHR individuals were assessed with the Comprehensive Assessment of At-Risk Mental States, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Partial least-squares correlation analysis (PLSC) was used as statistical method.RESULTS: PLSC group comparisons revealed one significant latent variable (LV) accounting for 52% of the cross-block covariance. This LV indicated a pattern of lower fractional anisotropy (FA), axial diffusivity (AD), and mode of anisotropy (MO) concomitant with higher radial diffusivity (RD) in widespread brain regions in UHR individuals compared with HCs. Within UHR individuals, PLSC revealed five significant LVs associated with symptoms and level of functioning. The first LV accounted for 31% of the cross-block covariance and indicated a pattern where higher symptom score and lower level of functioning correlated to lower FA, AD, MO, and higher RD.CONCLUSIONS: UHR individuals demonstrate complex brain patterns of WM abnormalities. Despite the subtle psychopathology of UHR individuals, aberrations in WM appear associated with positive and negative symptoms as well as level of functioning.

KW - Journal Article

U2 - 10.1017/S0033291717001210

DO - 10.1017/S0033291717001210

M3 - Journal article

C2 - 28464976

SN - 0033-2917

VL - 47

SP - 2689

EP - 2707

JO - Psychological Medicine

JF - Psychological Medicine

IS - 15

ER -