White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies
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Updated: Feb 21, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Enrico Vitolo1, Mona Karina Tatu1, Claudia Pignolo1
1Department of Psychology, University of Turin, Via Po 14, 10123 Turin, TO, Italy.
Abstract:
Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions.
Insights
Schizophrenia involves widespread white matter (WM) disruption, particularly affecting long projection fibers and fronto-temporal-limbic pathways. This meta-analysis clarifies the role of WM alterations in schizophrenia using voxel-based morphometry and diffusion tensor imaging.
Area of Science:
- Neuroimaging
- Psychiatry
- Neuroscience
Background:
- White matter (WM) alterations are implicated in mental disorders, but their specific role in schizophrenia remains unclear.
- Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are key neuroimaging techniques for assessing gray and white matter changes.
Purpose of the Study:
- To clarify the role of white matter disruption in schizophrenia.
- To identify the most frequently affected brain networks in schizophrenia using meta-analysis.
Main Methods:
- Systematic literature search for VBM and DTI studies comparing schizophrenia patients and controls.
- Anatomical Likelihood Estimation (ALE) meta-analysis of studies reporting WM reductions.
- Labeling of WM bundles using an anatomical atlas and comparison of VBM and DTI ALE scores.
Main Results:
- A total of 59 studies were included in the meta-analysis.
- WM alterations were identified in 31 foci using VBM and 34 foci using DTI.
- The most frequently affected WM bundles included long projection fibers, callosal/commissural fibers, motor pathways, and fronto-temporal-limbic pathways.
Conclusions:
- Schizophrenia is characterized by widespread white matter disruption, not confined to specific regions.
- The findings highlight the involvement of specific cerebral circuits, particularly long projection and fronto-temporal-limbic pathways, in schizophrenia pathophysiology.
