Shared Social Brain Gray Matter Reductions in Depression, Schizophrenia, and Alcohol Use Disorder: A Meta-Analysis
- 1The University of Hong Kong
Abstract
ImportanceAnhedonia, social withdrawal and executive deficits represent transdiagnostic symptoms in depression, schizophrenia and addition, yet transdiagnostic brain volumetric alterations and their contribution to these symptom domains have not been systematically characterized.
ObjectiveTo determine common and disorder-specific gray matter deficits in patients with schizophrenia (SZ), major depression disorder (MDD) and alcohol use disorder (AUD) compared to heathy controls.
Data SourcesA comprehensive literature search using three databases including PubMed, Web of Science and PsycInfo (between January 2000 to March 2024) as well as searches on review articles.
Study SelectionStudies had to be published in English, reporting whole-brain results, comparing patients and healthy controls.
Data Extraction and SynthesisThis meta-analysis adhered to the PRISMA guidelines and was pre-registered (https://osf.io/s57uq) prior to data analysis. Data was independently extracted and verified by 3 contributors, and statistical brain maps were generated using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) random-effects model. 147 VBM studies encompassing 90 Schizophrenia, 44 MDD and 13 AUD studies were finally included.
Main Outcomes and MeasuresStatistical maps of common and disorder-specific gray matter deficits in patients versus healthy controls are presented. Statistical inference utilized permutation tests, with threshold at p < .0025 and cluster extent of 10 voxels. Heterogeneity was evaluated using the I2 statistic and publication bias using Eggers regression test.
ResultsCapitalizing on a coordinate-based meta-analysis involving n=13,041 participants, we found shared GMV alterations in the ventromedial prefrontal cortex, ventral anterior cingulate cortex, insula, superior temporal gyrus. On the network level, we found robust functional interactions of the identified shared regions with the cortical midline structures as well as social and theory of mind-related behavioral functions. Subsequent characterization analyses highlighted the involvement of dopaminergic and serotonergic neurotransmitters as well as associated genetic annotations.
Conclusions and RelevanceOverall, the present meta-analysis found common as well as separate GMV abnormalities in schizophrenia, major depressive disorder and alcohol use disorder suggesting a common neurostructural substrate and treatment target for social withdrawal and anhedonia across these disorders.
Key pointsO_ST_ABSQuestionC_ST_ABSCan transdiagnostic meta-analytic mapping identify common gray matter alterations associated with shared reward-related, social, and executive symptoms across major depressive disorder, schizophrenia, and alcohol use disorder?
FindingsThe meta-analysis determined transdiagnostic gray matter volume reductions in the ventromedial prefrontal cortex, ventral anterior cingulate cortex, insula, superior temporal gyrus. We found robust functional interactions of these regions with cortical midline structures including social and theory of mind related functions, while transcriptomic characterization highlighted the involvement of neurotransmitter systems and shared genetic markers.
MeaningThe study demonstrates regional-specific transdiagnostic brain structural alterations that may mediate social dysfunction and anhedonia across disorders.
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BibTeX
@misc{bore2026shared,
title = {{Shared Social Brain Gray Matter Reductions in Depression, Schizophrenia, and Alcohol Use Disorder: A Meta-Analysis}},
author = {M. C. Bore and J. He and M. Han and A. T. Hagan and X. Liu and J. Zhang and K. Kendrick and X. Huang and J. Yang and B. Klugah-Brown and B. Becker},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.26365862},
url = {https://www.medrxiv.org/content/10.64898/2026.10.18.26365862v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Shared Social Brain Gray Matter Reductions in Depression, Schizophrenia, and Alcohol Use Disorder: A Meta-Analysis
AU - M. C. Bore
AU - J. He
AU - M. Han
AU - A. T. Hagan
AU - X. Liu
AU - J. Zhang
AU - K. Kendrick
AU - X. Huang
AU - J. Yang
AU - B. Klugah-Brown
AU - B. Becker
PY - 2026
DA - 2026/10/18
PB - medRxiv
DO - 10.64898/2026.10.18.26365862
UR - https://www.medrxiv.org/content/10.64898/2026.10.18.26365862v1
AB - ImportanceAnhedonia, social withdrawal and executive deficits represent transdiagnostic symptoms in depression, schizophrenia and addition, yet transdiagnostic brain volumetric alterations and their contribution to these symptom domains have not been systematically characterized. ObjectiveTo determine common and disorder-specific gray matter deficits in patients with schizophrenia (SZ), major depression disorder (MDD) and alcohol use disorder (AUD) compared to heathy controls. Data SourcesA comprehensive literature search using three databases including PubMed, Web of Science and PsycInfo (between January 2000 to March 2024) as well as searches on review articles. Study SelectionStudies had to be published in English, reporting whole-brain results, comparing patients and healthy controls. Data Extraction and SynthesisThis meta-analysis adhered to the PRISMA guidelines and was pre-registered (https://osf.io/s57uq) prior to data analysis. Data was independently extracted and verified by 3 contributors, and statistical brain maps were generated using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) random-effects model. 147 VBM studies encompassing 90 Schizophrenia, 44 MDD and 13 AUD studies were finally included. Main Outcomes and MeasuresStatistical maps of common and disorder-specific gray matter deficits in patients versus healthy controls are presented. Statistical inference utilized permutation tests, with threshold at p < .0025 and cluster extent of 10 voxels. Heterogeneity was evaluated using the I2 statistic and publication bias using Eggers regression test. ResultsCapitalizing on a coordinate-based meta-analysis involving n=13,041 participants, we found shared GMV alterations in the ventromedial prefrontal cortex, ventral anterior cingulate cortex, insula, superior temporal gyrus. On the network level, we found robust functional interactions of the identified shared regions with the cortical midline structures as well as social and theory of mind-related behavioral functions. Subsequent characterization analyses highlighted the involvement of dopaminergic and serotonergic neurotransmitters as well as associated genetic annotations. Conclusions and RelevanceOverall, the present meta-analysis found common as well as separate GMV abnormalities in schizophrenia, major depressive disorder and alcohol use disorder suggesting a common neurostructural substrate and treatment target for social withdrawal and anhedonia across these disorders. Key pointsO_ST_ABSQuestionC_ST_ABSCan transdiagnostic meta-analytic mapping identify common gray matter alterations associated with shared reward-related, social, and executive symptoms across major depressive disorder, schizophrenia, and alcohol use disorder? FindingsThe meta-analysis determined transdiagnostic gray matter volume reductions in the ventromedial prefrontal cortex, ventral anterior cingulate cortex, insula, superior temporal gyrus. We found robust functional interactions of these regions with cortical midline structures including social and theory of mind related functions, while transcriptomic characterization highlighted the involvement of neurotransmitter systems and shared genetic markers. MeaningThe study demonstrates regional-specific transdiagnostic brain structural alterations that may mediate social dysfunction and anhedonia across disorders.
ER -