Evidence for Network-Based Cortical Thickness Reductions in Schizophrenia.

Cassandra M J Wannan Vanessa L Cropley M Mallar Chakravarty Chad Bousman Eleni P Ganella Jason M Bruggemann Thomas W Weickert Cynthia Shannon Weickert Ian Everall Patrick McGorry Dennis Velakoulis Stephen J Wood Cali F Bartholomeusz Christos Pantelis Andrew Zalesky

Am J Psychiatry

The Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia (Wannan, Cropley, Bousman, Ganella, T.W. Weickert, C.S. Weickert, McGorry, Velakoulis, Bartholomeusz, Pantelis, Zalesky); Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia (Wannan, Ganella, McGorry, Wood, Bartholomeusz); the Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia (Wannan, Ganella, McGorry, Wood, Bartholomeusz); the Cooperative Research Centre for Mental Health, Victoria, Australia (Wannan, Bousman, Ganella, Everall, Pantelis); North Western Mental Health, Melbourne Health, Parkville, Victoria, Australia (Wannan, Ganella, Everall, Pantelis); Faculty of Health, Arts, and Design, the Brain and Psychological Sciences Research Centre, Swinburne University, Victoria, Australia (Cropley); the Florey Institute for Neurosciences and Mental Health, Parkville, Victoria, Australia (Bousman, Everall, Pantelis); the Department of Electrical and Electronic Engineering, Centre for Neural Engineering, University of Melbourne, Carlton South, Victoria, Australia (Everall, Pantelis); the Melbourne School of Engineering, University of Melbourne, Parkville, Victoria, Australia (Everall, Pantelis, Zalesky); Alberta Children's Hospital Research Institute, University of Calgary, Alberta (Bousman); Hotchkiss Brain Institute, University of Calgary, Alberta (Bousman); the Departments of Medical Genetics, Psychiatry, and Physiology and Pharmacology, University of Calgary, Alberta (Bousman); the Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal (Chakravarty); the Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal (Chakravarty); the School of Psychiatry, University of New South Wales, Sydney, Australia (Bruggemann, T.W. Weickert, C.S. Weickert); Neuroscience Research Australia, Sydney, Australia (Bruggemann, T.W. Weickert, C.S. Weickert); the Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, New South Wales, Australia (T.W. Weickert, C.S. Weickert); the School of Psychology, University of Birmingham, Edgbaston, U.K. (Wood); the Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, N.Y. (T.W. Weickert, C.S. Weickert); and the Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Everall).

Published: July 2019

- The study aimed to explore the relationship between cortical thickness reductions and cortical connectivity networks in schizophrenia, hypothesizing that areas with reduced thickness are well interconnected, forming a network.
- Researchers analyzed structural brain images from three groups: patients with first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia, comparing their cortical thickness to healthy controls across 148 regions of the cortex.
- Findings revealed significant reductions in cortical thickness, especially in the chronic and treatment-resistant groups, with notable decreases in frontal, temporal, cingulate, and insular regions, and highlighted stronger structural connectivity among the affected areas compared to randomly selected ones.

Objective: Cortical thickness reductions in schizophrenia are irregularly distributed across multiple loci. The authors hypothesized that cortical connectivity networks would explain the distribution of cortical thickness reductions across the cortex, and, specifically, that cortico-cortical connectivity between loci with these reductions would be exceptionally strong and form an interconnected network. This hypothesis was tested in three cross-sectional schizophrenia cohorts: first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia.

Methods: Structural brain images were acquired for 70 patients with first-episode psychosis, 153 patients with chronic schizophrenia, and 47 patients with treatment-resistant schizophrenia and in matching healthy control groups (N=57, N=168, and N=54, respectively). Cortical thickness was compared between the patient and respective control groups at 148 regions spanning the cortex. Structural connectivity strength between pairs of cortical regions was quantified with structural covariance analysis. Connectivity strength between regions with cortical thickness reductions was compared with connectivity strength between 5,000 sets of randomly chosen regions to establish whether regions with reductions were interconnected more strongly than would be expected by chance.

Results: Significant (false discovery rate corrected) and widespread cortical thickness reductions were found in the chronic schizophrenia (79 regions) and treatment-resistant schizophrenia (106 regions) groups, with more circumscribed reductions in the first-episode psychosis group (34 regions). Cortical thickness reductions with the largest effect sizes were found in frontal, temporal, cingulate, and insular regions. In all cohorts, both the patient and healthy control groups showed significantly increased structural covariance between regions with cortical thickness reductions compared with randomly selected regions.

Conclusions: Brain network architecture can explain the irregular topographic distribution of cortical thickness reductions in schizophrenia. This finding, replicated in three distinct schizophrenia cohorts, suggests that the effect is robust and independent of illness stage.

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http://dx.doi.org/10.1176/appi.ajp.2019.18040380	DOI Listing

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