Structural brain abnormalities and aggression in schizophrenia: mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium

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Contributors

  • ENIGMA Schizophrenia Consortium - (Author)
  • Division of Psychological and Social Medicine and Developmental Neurosciences
  • Department of Child and Adolescent Psychiatry and Psychotherapy
  • Vrije Universiteit Amsterdam (VU)
  • Utrecht University
  • University of Pennsylvania
  • University of Pennsylvania Perelman School of Medicine
  • Tilburg University
  • Radboud University Nijmegen
  • IRCCS Fondazione Santa Lucia - Roma
  • Universita' di Napoli Federico II
  • University of Marburg
  • Feinstein Institutes for Medical Research
  • Georgia State University
  • Singapore Institute of Mental Health
  • Seoul National University
  • Jeonbuk National University
  • Brigham Young University
  • University of Münster
  • King's College London (KCL)
  • University of Montreal
  • University of Zurich
  • Harvard University
  • Institute of Living
  • Neuroscience Research Australia
  • University of New South Wales
  • Hospital Benito Menni
  • University of Texas Health Science Center at Houston
  • Geneva University Hospitals
  • Russian Academy of Medical Sciences
  • Sisters Hospitallers Research Foundation
  • McGill University Health Centre
  • University of Lübeck
  • Imperial College London

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

Original languageEnglish
Pages (from-to)2273-2282
Number of pages10
JournalMolecular psychiatry
Volume31
Issue number4
Publication statusPublished - Apr 2026
Peer-reviewedYes

External IDs

PubMed 41339704
ORCID /0000-0003-2132-4445/work/222089361
ORCID /0000-0001-8029-8270/work/222089417