Systematic Meta-Analysis of Insula Volume in Schizophrenia
Abstract
Background Volume reduction in insular cortex may constitute an important neuropathology in schizophrenia. We provide the first meta-analysis of studies that conducted region-of-interest analyses of the magnitude of effect and pattern of insula volume reduction in schizophrenia compared with healthy control subjects. Methods Included studies examined insula volume in schizophrenia relative to healthy control subjects. Studies were located via electronic database searches and hand searching. Study selection, data extraction, and quality assessment were completed by two independent reviewers. Hedge's g effect sizes were calculated using Comprehensive Meta-Analysis (v.2) to quantify volumetric differences between people with and without schizophrenia, accounting for moderating influences of age, sex, illness duration, medication, whole brain volume, and potential differences in hemispheric and anatomical subregions. Results Random-effects analysis showed reductions of bilateral insula (n = 945, g = -.446, 95% confidence interval -.639 to -.252, p = .00001), with moderate heterogeneity apparent (I² = 76%). This effect was consistent across left and right insula and not influenced by illness stage or sex. Additional analyses revealed larger reductions of anterior (n = 605, g = -.643, p < 0.001; I² = 52%) than of posterior insula (n = 453, g = -.321, p = .028; I² = 55%). Meta-regression analyses did not identify any significant predictors of reduced insula volume. Conclusions This meta-analysis indicates medium-sized reduction of insula volume in schizophrenia, of greatest magnitude in the anterior subregion. Cellular distinctions across anterior and posterior insula may contribute to understanding the neuropathology and functional significance of the observed volumetric differences.
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All included studies were evaluated with a 12-point Imaging Methodology Quality Assessment Checklist.
“We evaluated all included studies with a 12-point Imaging Methodology Quality Assessment Checklist for their quality and limitations to infer the importance of those findings (Shepherd, Matheson, Laurens, Carr, & Green, 2012)”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Shepherd, Matheson, Laurens, Carr, & Green, 2012
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“We evaluated all included studies with a 12-point Imaging Methodology Quality Assessment Checklist for their quality and limitations to infer the importance of those findings (Shepherd, Matheson, Laurens, Carr, & Green, 2012) (for details, see Online Supplementary Appendix 3).”
- Authors
- Shepherd, A. M., Matheson, S. L., Laurens, K. R., Carr, V. J., & Green, M. J.
- Affiliations
- UNSW Sydney (AU)
- King's College London (GB)
- Corresponding author
- Shepherd, Alana M.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 72
- Issue
- 9
- Pages
- 775-784
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2008427705
- Cited by
- 207
- References
- 9
- Citations by year
- 2026: 25 · 2025: 16 · 2024: 20 · 2023: 15 · 2022: 23 · 2021: 17 · 2020: 14 · 2019: 15 · 2018: 8 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 11 · 2013: 6 · 2012: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- schizophrenia, insula, brain volumetry, anterior insula, posterior insula, regional brain atrophy, effect size heterogeneity
- MeSH terms
- Atrophy, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Schizophrenia, Case-Control Studies, Cerebrum, Neuroimaging
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