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

Published online by Cambridge University Press:  03 May 2017

K. Krakauer ,
B. H. Ebdrup ,
B. Y. Glenthøj ,
J. M. Raghava ,
D. Nordholm ,
L. Randers ,
E. Rostrup  and
M. Nordentoft
K. Krakauer*
Affiliation:
Mental Health Centre Copenhagen, Copenhagen University Hospital, DK-2900 Hellerup, Denmark Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark Functional Imaging Unit, Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, DK-2600 Glostrup, Denmark
B. H. Ebdrup
Affiliation:
Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Denmark
B. Y. Glenthøj
Affiliation:
Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Denmark
J. M. Raghava
Affiliation:
Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark Functional Imaging Unit, Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, DK-2600 Glostrup, Denmark Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Denmark
D. Nordholm
Affiliation:
Mental Health Centre Copenhagen, Copenhagen University Hospital, DK-2900 Hellerup, Denmark Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark
L. Randers
Affiliation:
Mental Health Centre Copenhagen, Copenhagen University Hospital, DK-2900 Hellerup, Denmark Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark
E. Rostrup
Affiliation:
Functional Imaging Unit, Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, DK-2600 Glostrup, Denmark
M. Nordentoft
Affiliation:
Mental Health Centre Copenhagen, Copenhagen University Hospital, DK-2900 Hellerup, Denmark Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, Denmark
*
*Address for correspondence: K. Krakauer, M.D., Research Unit, Mental Health Centre Copenhagen, Gentofte Hospital, Kildegårdsvej 28, Opgang 15, 4. sal, 2900 Hellerup, Denmark. (Email: kristine.krakauer@regionh.dk)
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Abstract

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.

Keywords

Diffusion tensor imaginglevel of functioningPartial Least Squares correlation analysispsychopathologyultra high-risk for psychosis
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 15 , November 2017 , pp. 2689 - 2707
Copyright
Copyright © Cambridge University Press 2017 

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