The magnitude and variability of brain structural alterations in bipolar disorder: A double meta-analysis of 5534 patients and 6651 healthy controls

Ilinca Angelescu*, Stefan P. Brugger, Faith Borgan, Stephen J. Kaar, Oliver D. Howes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)

Abstract

Background: Bipolar disorder is thought to be associated with structural brain alterations, but findings have been inconsistent. Our double meta-analysis investigated the variability and magnitude of differences in regional brain volumes in patients with bipolar disorder relative to healthy volunteers. Methods: Databases were systematically searched for MRI studies reporting regional brain volumetric measures in patients with bipolar disorder and controls. The primary outcome measures were variability ratio (VR), coefficient of variability ratio (CVR) and Hedge's g. Results: 118 studies comprising 5534 patients and 6651 controls were included. The variability meta-analysis showed higher variability in amygdala (VR, 1.14; P =.02; CVR, 1.25; P =.005) and hippocampal (VR, 1.16; P =.001; CVR, 1.22; P = <.001) volumes in patients relative to controls. The meta-analysis of volume differences showed higher lateral (g, -0.43; P = <.0001) and third ventricle (g, -0.22; P =.01) volumes in patients; and lower hippocampus (g, 0.41; P =.001), grey matter (g, 0.25; P =.001), white matter (g, 0.23; P =.0002) and total brain volumes (g, 0.20; P =.003) in patients relative to controls. A higher proportion of male subjects was associated with decreased mean volumes of the amygdala, hippocampus and thalamus and increased lateral ventricle volumes. Limitations: There was significant publication bias and between-study inconsistency for several brain regions. Conclusions: Bipolar disorder is associated with generalised alterations in white and grey matter brain volumes, particularly marked in the hippocampus volumes, which were smaller but showed greater variability in volumes relative to controls. This suggests that heterogeneity in neurobiological processes involving the hippocampus contribute to clinical heterogeneity in the disorder, and this may be more marked in males than females.

Original languageEnglish
Pages (from-to)171-176
Number of pages6
JournalJournal of Affective Disorders
Volume291
DOIs
Publication statusPublished - 1 Aug 2021

Keywords

  • Bipolar disorder
  • Heterogeneity
  • Meta-analysis
  • Subcortical
  • Variability
  • Volume

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