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Updated: Jun 17, 2026

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Published on: September 8, 2021
Anatomy of bipolar disorder and schizophrenia: a meta-analysis
Ian Ellison-Wright1, Ed Bullmore
1Brain Mapping Unit, University of Cambridge, Cambridge, UK. ian.ellison-wright@awp.nhs.uk
Background:
Recent genetic results have indicated that the two major, classically distinct forms of psychosis - schizophrenia and bipolar disorder - may share causative factors in common. However it is not clear to what extent they may also have similar profiles of brain abnormality. We used meta-analytic techniques to generate and compare maps of brain structural abnormality in the large samples of patients with both disorders that have been studied using magnetic resonance imaging.
Method:
A systematic search was conducted for voxel-based morphometry studies examining gray matter in patients with schizophrenia or bipolar disorder. The anatomical distribution of the co-ordinates of gray matter differences was meta-analysed using Anatomical Likelihood Estimation.
Results:
Forty-two schizophrenia studies including 2058 patients with schizophrenia and 2131 comparison subjects were compared with fourteen bipolar studies including 366 patients with bipolar disorder and 497 comparison subjects. In schizophrenia, there were extensive gray matter deficits in frontal, temporal, cingulate and insular cortex and thalamus, and increased gray matter in the basal ganglia. In bipolar disorder, gray matter reductions were present in the anterior cingulate and bilateral insula. These substantially overlapped with areas of gray matter reduction in schizophrenia, except for a region of anterior cingulate where gray matter reduction was specific to bipolar disorder.
Implications:
In bipolar disorder studies there were consistent regional gray matter reductions in paralimbic regions (anterior cingulate and insula) implicated in emotional processing. Gray matter reductions in schizophrenia studies were more extensive and involved limbic and neocortical structures as well as the paralimbic regions affected in bipolar disorder.
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