Journal article
Structural brain abnormalities and aggression in schizophrenia: mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium
Molecular psychiatry, Vol.31(5), pp.2273-2282
05/2026
DOI: 10.1038/s41380-025-03365-7
PMID: 41339704
Abstract
It is hypothesised that structural brain abnormalities in individuals with schizophrenia are associated with aggressive behaviour, but this has not been tested directly. We pooled magnetic resonance imaging and clinical data from 2095 patients and 2861 healthy control subjects across 20 sites of the ENIGMA-Schizophrenia Working Group. Using normative modelling, we quantified individual-level deviations from controls (z-scores) for global and regional grey matter volume and white matter microstructural integrity. Ordinal regression models were used to estimate the associations between these deviations and concurrent aggression (odds ratios [ORs] with 99% confidence intervals [CIs]). In mediation analyses, we examined the roles of positive symptoms – delusions, hallucinations and disorganised thinking – impulsivity and illness insight. Aggression was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = 0.003), global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10−5), dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p = 0.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10−7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10−4). These associations were robust to adjustment for relevant covariates and partly mediated by positive symptoms and impulsivity. Our findings suggest that the co-occurrence of positive symptoms, impulsivity and aggression in schizophrenia has a neurobiological basis, providing potential targets for therapeutic interventions.
Details
- Title: Subtitle
- Structural brain abnormalities and aggression in schizophrenia: mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium
- Creators
- Jelle Lamsma - University Medical Center UtrechtAdrian Raine - University of PennsylvaniaSeyed M Kia - Radboud University NijmegenWiepke Cahn - University Medical Center UtrechtDominic Arold - Technische Universität DresdenNerisa Banaj - Fondazione Santa LuciaAnnarita Barone - University of Naples Federico IIKatharina Brosch - Feinstein Institute for Medical ResearchRachel Brouwer - Vrije Universiteit AmsterdamArturo Brunetti - University of Naples Federico IIVince D Calhoun - Georgia State UniversityQian H Chew - Institute of Mental HealthSunah Choi - Seoul National UniversityYoung-Chul Chung - Jeonbuk National University HospitalMariateresa Ciccarelli - University of Naples Federico IIDerin Cobia - Brigham Young UniversitySirio Cocozza - University of Naples Federico IIUdo Dannlowski - University of MünsterPaola Dazzan - King's College LondonAndrea de Bartolomeis - University of Naples Federico IIMarta Di Forti - King's College LondonAlexandre Dumais - Institut national de psychiatrie légale Philippe-PinelJesse T Edmond - Georgia State UniversityStefan Ehrlich - Technische Universität DresdenUlrika Evermann - Philipps University of MarburgKira Flinkenflügel - University of MünsterFoivos Georgiadis - University of ZurichDavid C Glahn - Harvard Medical SchoolJanik Goltermann - University of MünsterMelissa J Green - UNSW SydneyDominik Grotegerd - University of MünsterAmalia Guerrero-Pedraza - Hospital Benito Menni CASM, Barcelona, SpainMinji Ha - Seoul National UniversityElliot L Hong - The University of Texas Health Science Center at HoustonHilleke Hulshoff Pol - Utrecht UniversityFelice Iasevoli - University of Naples Federico IIStefan Kaiser - University Hospital of GenevaVasily Kaleda - Mental Health Research Center of Russian Academy of Medical SciencesAndriana Karuk - Fidmag Sisters HospitallersMinah Kim - Seoul National UniversityTilo Kircher - Philipps University of MarburgMatthias Kirschner - McGill UniversityPeter Kochunov - The University of Texas Health Science Center at HoustonJun Soo Kwon - Seoul National UniversityIrina Lebedeva - Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, RussiaRebekka Lencer - University of LübeckTiago R Marques - Imperial College LondonSusanne Meinert - University of MünsterRobin Murray - King's College LondonIgor Nenadić - Philipps University of MarburgDana Nguyen - University of California, IrvineGodfrey Pearlson - Franklin W. Olin College of EngineeringFabrizio Piras - Fondazione Santa LuciaEdith Pomarol-Clotet - Centro de Investigación Biomédica en Red de Salud MentalGiuseppe Pontillo - University of Naples Federico IIStéphane Potvin - Institut universitaire en santé mentale de MontréalAdrian Preda - University of California, IrvineYann Quidé - UNSW SydneyAmanda Rodrigue - Harvard Medical SchoolKelly Rootes-Murdy - Georgia State UniversityRaymond Salvador - Centro de Investigación Biomédica en Red de Salud MentalKang Sim - Institute of Mental HealthAntonin Skoch - National Institute of Mental HealthGianfranco Spalletta - Fondazione Santa LuciaFilip Spaniel - National Institute of Mental HealthFrederike Stein - Philipps University of MarburgFlorian Thomas-Odenthal - Philipps University of MarburgAndràs Tikàsz - Institut universitaire en santé mentale de MontréalDavid Tomecek - Czech Technical University in PragueAlexander Tomyshev - Mental Health Research Center of Russian Academy of Medical SciencesMario Tranfa - University of Naples Federico IIUyanga Tsogt - Jeonbuk National UniversityJessica A Turner - The Ohio State University Wexner Medical CenterTheo G M van Erp - University of California, IrvineNeeltje E M van Haren - Erasmus MCJim van Os - Maastricht UniversityDaniela Vecchio - Fondazione Santa LuciaLei Wang - Northwestern UniversityAdrian Wroblewski - Philipps University of MarburgThomas Nickl-Jockschat - Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.31(5), pp.2273-2282
- DOI
- 10.1038/s41380-025-03365-7
- PMID
- 41339704
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Publisher
- Springer Nature
- Grant note
- Richard Perry University ProfessorshipAndrew H. Woods Professorship
The ENIGMA project is supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH) under grant number U54EB020403. Funding information for the participating sites can be found in the supplement. AR is supported by the Richard Perry University Professorship and TN-J by the Andrew H. Woods Professorship. The funders had no role in study design, data collection or analysis, decision to publish or the preparation of the manuscript.
- Language
- English
- Electronic publication date
- 12/03/2025
- Date published
- 05/2026
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9985090728902771
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