Open Access Highly Accessed Research article

Distribution of tract deficits in schizophrenia

Ian Ellison-Wright12*, Pradeep J Nathan1114, Edward T Bullmore13, Rashid Zaman56, Robert B Dudas57, Mark Agius56, Emilio Fernandez-Egea578, Ulrich Müller17, Chris M Dodds3, Natalie J Forde9, Cathy Scanlon9, Alexander Leemans10, Colm McDonald9 and Dara M Cannon9

Author Affiliations

1 Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Herchel Smith Building for Brain and Mind Sciences, Robinson Way, Cambridge CB2 0SZ, UK

2 Avon and Wiltshire Mental Health Partnership NHS Trust, Heathwood, Fountain Way, Salisbury SP2 7FD, UK

3 GlaxoSmithKline, Clinical Unit Cambridge (CUC), Addenbrooke’s Centre for Clinical Investigation (ACCI), Addenbrooke’s Hospital, Hills Road, PO Box 128, Cambridge CB2 0GG, UK

4 School of Psychology and Psychiatry, Monash University, Building 17, Clayton Campus, Wellington Road, Clayton, VIC 3800, Australia

5 Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Box 189, Cambridge CB2 2QQ, UK

6 South Essex Partnership University NHS Foundation Trust (SEPT), The Lodge, The Chase, Wickford, Essex SS11 7XX, United Kingdom

7 Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge CB21 5EF, UK

8 Behavioural Clinical Neuroscience Institute (BCNI), University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Box 189, Cambridge CB2 2QQ, UK

9 Clinical Neuroimaging Laboratory, Departments of Anatomy & Psychiatry, College of Medicine, Nursing and Health Sciences, 202 Comerford Suite, Clinical Sciences Institute, National University of Ireland, Galway, Republic of Ireland

10 Image Sciences Institute, University Medical Center Utrecht, Q.S.459, P.O. Box 85500, 3508 GA Utrecht, The Netherlands

11 New Medicines, UCB Pharma, Chemin du Foriest B-1420, Braine-l'Alleud, Belgium

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BMC Psychiatry 2014, 14:99  doi:10.1186/1471-244X-14-99

Published: 2 April 2014



Gray and white matter brain changes have been found in schizophrenia but the anatomical organizing process underlying these changes remains unknown. We aimed to identify gray and white matter volumetric changes in a group of patients with schizophrenia and to quantify the distribution of white matter tract changes using a novel approach which applied three complementary analyses to diffusion imaging data.


21 patients with schizophrenia and 21 matched control subjects underwent brain magnetic resonance imaging. Gray and white matter volume differences were investigated using Voxel-based Morphometry (VBM). White matter diffusion changes were located using Tract Based Spatial Statistics (TBSS) and quantified within a standard atlas. Tracts where significant regional differences were located were examined using fiber tractography.


No significant differences in gray or white matter volumetry were found between the two groups. Using TBSS the schizophrenia group showed significantly lower fractional anisotropy (FA) compared to the controls in regions (false discovery rate <0.05) including the genu, body and splenium of the corpus callosum and the left anterior limb of the internal capsule (ALIC). Using fiber tractography, FA was significantly lower in schizophrenia in the corpus callosum genu (p = 0.003).


In schizophrenia, white matter diffusion deficits are prominent in medial frontal regions. These changes are consistent with the results of previous studies which have detected white matter changes in these areas. The pathology of schizophrenia may preferentially affect the prefrontal-thalamic white matter circuits traversing these regions.

Schizophrenia; Diffusion tensor imaging; Tract based spatial statistics; Voxel based morphometry; Gray matter; White matter