Mapping grey matter reductions in schizophrenia: An anatomical likelihood estimation analysis of voxel-based morphometry studies

doi:10.1016/j.schres.2008.12.011

Schizophrenia Research

Volume 108, Issues 1–3, March 2009, Pages 104-113

https://doi.org/10.1016/j.schres.2008.12.011 Get rights and content

Abstract

Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.

Section snippets

Study selection

Studies were identified through PubMed and PsycINFO using either schizo⁎ or psychosis or psychotic and one of the following terms as keywords; MRI, brain, VBM, voxel, volume. Their reference lists were crosschecked to identify further relevant papers. Studies were included if they met the following criteria: (1) they were published, in English, prior to August 2008; (2) they reported results for at least one cross-sectional VBM comparison between schizophrenia patients and healthy controls

Pooled analysis

ALE analysis of all foci identified fifteen significant clusters encompassing frontal, temporal, limbic, and subcortical regions (Table 2; Fig. 1). The largest clusters were in the anterior cingulate/medial prefrontal cortex and insula/operculum bilaterally. Bilateral reductions were also observed in the thalamus, posterior cingulate, medial temporal lobes and the subgenual cingulate cortex extending into the right caudate. Left-lateralized reductions were identified in the posterior and

Discussion

This study extends recent meta-analyses of the VBM literature (Ellison-Wright et al., 2008, Glahn et al., 2008, Honea et al., 2005) in schizophrenia by conducting an ALE analysis in an expanded sample of 37 studies, incorporating data from an additional 451 patients and 428 controls. Our findings are consistent with these previous analyses, and implicate a network of frontal, temporal, limbic, thalamic and striatal regions as those most frequently showing grey matter reductions in patients with

Role of funding source

This research was supported by the Melbourne Neuropsychiatry Centre (Sunshine Hospital), Department of Psychiatry, the University of Melbourne, Melbourne Health, the National Health and Medical Research Council (ID 236175; 350241), and the Ian Potter Foundation. AF was supported by a JN Peters Fellowship and NHMRC CJ Martin Fellowship (ID: 454797). MY was supported by NHMRC Program Grant (ID: 350241) and NHMRC Clinical Career Development Award (ID: 509345). SJW was supported by a NHMRC Clinical

Contributors

AF designed the study and wrote the first draft of the manuscript. JP assisted with data collection and writing the paper. MY, SJW and CP assisted with the study design, analysis and manuscript writing. All authors contributed to and have approved the final draft of the manuscript.

Conflict of interest

None.

Acknowledgement

The authors would like to thank Ms. Bridget Soulsby, who facilitated all analyses.

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Mapping grey matter reductions in schizophrenia: An anatomical likelihood estimation analysis of voxel-based morphometry studies

Abstract

Section snippets

Study selection

Pooled analysis

Discussion

Role of funding source

Contributors

Conflict of interest

Acknowledgement

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