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The effects of gender on grey matter abnormalities in major psychoses: a comparative voxelwise meta-analysis of schizophrenia and bipolar disorder

Published online by Cambridge University Press:  11 August 2011

E. Bora*
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, VIC, Australia
A. Fornito
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, VIC, Australia
M. Yücel
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, VIC, Australia Orygen Research Centre, Melbourne, VIC, Australia
C. Pantelis
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, VIC, Australia
*Address for correspondence: Dr E. Bora, Alan Gilbert Building NNF level 3, Carlton 3053, Australia. (Email:



Recent evidence from genetic and familial studies revitalized the debate concerning the validity of the distinction between schizophrenia and bipolar disorder. Comparing brain imaging findings is an important avenue to examine similarities and differences and, therefore, the validity of the distinction between these conditions. However, in contrast to bipolar disorder, most patient samples in studies of schizophrenia are predominantly male. This a limiting factor for comparing schizophrenia and bipolar disorder since male gender is associated with more severe neurodevelopmental abnormalities, negative symptoms and cognitive deficits in schizophrenia.


We used a coordinate-based meta-analysis technique to compare grey matter (GM) abnormalities in male-dominated schizophrenia, gender-balanced schizophrenia and bipolar disorder samples based on published voxel-based morphometry (VBM) studies. In total, 72 English-language, peer reviewed articles published prior to January 2011 were included. All reports used VBM for comparing schizophrenia or bipolar disorder with controls and reported whole-brain analyses in standard stereotactic space.


GM reductions were more extensive in male-dominated schizophrenia compared to gender-balanced bipolar disorder and schizophrenia. In gender-balanced samples, GM reductions were less severe. Compared to controls, GM reductions were restricted to dorsal anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex in schizophrenia and ACC and bilateral fronto-insular cortex in bipolar disorder.


When gender is controlled, GM abnormalities in bipolar disorder and schizophrenia are mostly restricted to regions that have a role in emotional and cognitive aspects of salience respectively. Dorsomedial and dorsolateral prefrontal cortex were the only regions that showed greater GM reductions in schizophrenia compared to bipolar disorder.

Original Articles
Copyright © Cambridge University Press 2011

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Supplementary Fig. 1. Flow diagram for meta-analysis of voxelwise gray matter studies in schizophrenia and bipolar disorder

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