Grey matter differences in bipolar disorder: A meta-analysis of voxel-based morphometry studies

Sudhakar Selvaraj, Danilo Arnone, Dominic Job, Andrew Stanfield, Tom F.D. Farrow, Allison C. Nugent, Harald Scherk, Oliver Gruber, Xiaohua Chen, Perminder S. Sachdev, Daniel P. Dickstein, Gin S. Malhi, Tae H. Ha, Kyooseob Ha, Mary L. Phillips, Andrew M. McIntosh

Research output: Contribution to journalReview articlepeer-review

214 Citations (Scopus)


Objective: Several neuroimaging studies have reported structural brain differences in bipolar disorder using automated methods. While these studies have several advantages over those using region of interest techniques, no study has yet estimated a summary effect size or tested for between-study heterogeneity. We sought to address this issue using meta-analytic techniques applied for the first time in bipolar disorder at the level of the individual voxel. Methods: A systematic review identified 16 voxel-based morphometry (VBM) studies comparing individuals with bipolar disorder with unaffected controls, of which eight were included in the meta-analysis. In order to take account of heterogeneity, summary effect sizes were computed using a random-effects model with appropriate correction for multiple testing. Results: Compared with controls, subjects with bipolar disorder had reduced grey matter in a single cluster encompassing the right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study heterogeneity was widespread throughout the brain; though the significant cluster of grey matter reduction remained once these extraneous voxels had been removed. We found no evidence of publication bias (Eggers p = 0.63). Conclusions: Bipolar disorder is consistently associated with reductions in right prefrontal and temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and methodological heterogeneity.

Original languageEnglish
Pages (from-to)135-145
Number of pages11
JournalBipolar Disorders
Issue number2
Publication statusPublished - Mar 2012
Externally publishedYes


  • Bipolar disorder
  • Grey matter
  • Magnetic resonance imaging
  • Meta-analysis
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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