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White matter connectivity disruptions in early and chronic schizophrenia

Published online by Cambridge University Press:  22 May 2017

M. A. Di Biase*
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
V. L. Cropley
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
B. T. Baune
Affiliation:
Discipline of Psychiatry, The University of Adelaide, SA, Australia
J. Olver
Affiliation:
Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Discipline of Psychiatry, The University of Adelaide, SA, Australia Centre for PET, Austin Hospital, Heidelberg, VIC, Australia
G. P. Amminger
Affiliation:
Orygen, The National Centre of Excellence in Youth Mental Health, VIC, Australia Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia
C. Phassouliotis
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Cooperative Research Centre for Mental Health, Carlton, VIC, Australia
C. Bousman
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Cooperative Research Centre for Mental Health, Carlton, VIC, Australia Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia
P. D. McGorry
Affiliation:
Orygen, The National Centre of Excellence in Youth Mental Health, VIC, Australia Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia North Western Mental Health, Melbourne Health, Parkville, VIC, Australia
I. Everall
Affiliation:
Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Cooperative Research Centre for Mental Health, Carlton, VIC, Australia Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia North Western Mental Health, Melbourne Health, Parkville, VIC, Australia Department of Electrical and Electronic Engineering, Centre for Neural Engineering, University of Melbourne, Carlton South, VIC, Australia
C. Pantelis
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Discipline of Psychiatry, The University of Adelaide, SA, Australia Cooperative Research Centre for Mental Health, Carlton, VIC, Australia Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia North Western Mental Health, Melbourne Health, Parkville, VIC, Australia Department of Electrical and Electronic Engineering, Centre for Neural Engineering, University of Melbourne, Carlton South, VIC, Australia
A. Zalesky
Affiliation:
Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia Melbourne School of Engineering, The University of Melbourne, Parkville, VIC, Australia
*
*Address for correspondence: M. A. Di Biase, Melbourne Neuropsychiatry Centre, The University of Melbourne, Level 3, Alan Gilbert Building, Carlton South, VIC 3053, Australia. (Email: [email protected])

Abstract

Background

White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.

Methods

Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).

Results

Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).

Conclusions

Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

These authors are joint seniors.

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