Systematic Meta-Analysis of Insula Volume in Schizophrenia

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 (I-2 = 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; I-2 = 52%) than of posterior insula (n = 453, g = -.321, p = .028; I-2 = 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.