{ "abstract": "BackgroundAlthough most individuals with schizophrenia do not show aggressive behavior, rates are higher than in the general population. Identifying the neurobiological correlates of aggression may inform prevention.\n\nMethodsWe included 2260 individuals with schizophrenia spectrum disorders and 3058 healthy controls (HC) from 26 sites in the ENIGMA-Schizophrenia Working Group. The former were classified as showing at least moderate aggression (SZ+A; N = 231) or not (SZ-A; N = 2029) based on symptom rating scales. Structural covariance networks were constructed from cortical and subcortical volumes. We examined global and nodal network topology, as well as density within six large-scale brain networks and between each network and the rest of the brain. Metrics were summarized as the area under the curve (AUC) across a prespecified range of densities (K = 0.10-0.25, {Delta}K = 0.01). Group differences were assessed using pairwise permutation tests with Benjamini-Hochberg correction for multiple comparisons.\n\nResultsGlobal and nodal network topology did not differ significantly between SZ+A and HC. Network-rest density of the salience network (SN) was higher in SZ+A than in HC, although this difference did not survive multiple-comparison correction ({Delta}AUC = 0.018, pBH = .083). In exploratory subgroup analyses, higher SN network-rest density was observed only in SZ+A with high delusion severity ({Delta}AUC = 0.021, p = .007). By contrast, SZ-A demonstrated extensive alterations in global network topology compared with SZ+A and HC, alongside selective alterations in nodal topology and large-scale network density compared with HC. Results were broadly consistent across sensitivity analyses using alternative definitions of aggression and adjusting for current antipsychotic dose.\n\nConclusionsSZ+A was characterized by fewer--not more--abnormalities in structural covariance network organization than SZ-A, which may reflect etiological heterogeneity. In SZ+A with high delusion severity, higher network-rest density of the SN may point to aberrant salience processing in aggressive behavior.", "abstract_shown": true, "affiliations": [], "article_type": "PUBLISHAHEADOFPRINT", "arxiv": null, "author_total": 99, "authors": [ { "name": "Jelle Lamsma", "orcid": "0000-0003-3730-6153" }, { "name": "Paolo Fusar-Poli", "orcid": "0000-0003-3582-6788" }, { "name": "Martijn van den Heuvel", "orcid": "0000-0003-1570-1195" }, { "name": "Derin Cobia", "orcid": "0000-0003-2339-958X" }, { "name": "Adrian Raine", "orcid": "0000-0002-3756-4307" }, { "name": "Bin Wan", "orcid": "0000-0001-9077-3354" }, { "name": "Matthias Kirschner", "orcid": "0000-0002-9486-1439" }, { "name": "Wiepke Cahn", "orcid": "0000-0002-0482-8759" }, { "name": "Dominic Arold", "orcid": "0000-0001-8029-8270" }, { "name": "Mihai Avram", "orcid": "0000-0003-2171-8313" }, { "name": "Nerisa Banaj", "orcid": "0000-0002-6317-8549" }, { "name": "Annarita Barone", "orcid": "0000-0002-2751-5683" }, { "name": "Stefan Borgwardt", "orcid": "0000-0002-5792-3987" }, { "name": "Katharina Brosch", "orcid": "0000-0002-0526-8095" }, { "name": "Rachel M. Brouwer", "orcid": "0000-0002-7466-1544" }, { "name": "Arturo Brunetti", "orcid": "0000-0001-7057-3494" }, { "name": "Vince D. Calhoun", "orcid": "0000-0001-9058-0747" }, { "name": "Sean Carruthers", "orcid": "0000-0001-9140-3494" }, { "name": "Giacomo Cecere", "orcid": "0009-0003-1344-8787" }, { "name": "Simon Cervenka", "orcid": "0000-0001-8103-6977" }, { "name": "Qian H. Chew" }, { "name": "Sunah Choi", "orcid": "0000-0001-5666-3485" }, { "name": "Young-Chul Chung", "orcid": "0000-0001-9491-1822" }, { "name": "Mariateresa Ciccarelli", "orcid": "0000-0001-8944-414X" }, { "name": "Sirio Cocozza", "orcid": "0000-0002-0300-5160" }, { "name": "Benedicto Crespo-Facorro", "orcid": "0000-0003-0033-7132" }, { "name": "Udo Dannlowski", "orcid": "0000-0002-0623-3759" }, { "name": "Paola Dazzan", "orcid": "0000-0002-8427-3617" }, { "name": "Andrea de Bartolomeis", "orcid": "0000-0002-3188-5652" }, { "name": "Marta Di Forti", "orcid": "0000-0002-3218-6925" }, { "name": "Stefan Ehrlich", "orcid": "0000-0003-2132-4445" }, { "name": "Simone Elia" }, { "name": "Asia Ferrari", "orcid": "0009-0001-3227-9443" }, { "name": "Marc Fischer" }, { "name": "Kira Flinkenflügel", "orcid": "0000-0001-7738-5429" }, { "name": "David C. Glahn", "orcid": "0000-0002-4749-6977" }, { "name": "Janik Goltermann", "orcid": "0000-0003-3087-1002" }, { "name": "Melissa J. Green", "orcid": "0000-0002-9361-4874" }, { "name": "Dominik Grotegerd", "orcid": "0000-0001-8718-0128" }, { "name": "Oliver Gruber", "orcid": "0000-0003-1841-7413" }, { "name": "Amalia Guerrero-Pedraza" }, { "name": "Minji Ha", "orcid": "0000-0002-9840-6695" }, { "name": "Philipp Homan", "orcid": "0000-0001-9034-148X" }, { "name": "L. Elliot Hong", "orcid": "0009-0007-7576-969X" }, { "name": "Matthew Hughes", "orcid": "0000-0001-5057-5556" }, { "name": "Felice Iasevoli", "orcid": "0000-0002-7051-5013" }, { "name": "Stefan Kaiser" }, { "name": "Vasily Kaleda" }, { "name": "Andriana Karuk", "orcid": "0000-0002-2876-7268" }, { "name": "Minah Kim", "orcid": "0000-0001-8668-0817" }, { "name": "Tilo Kircher", "orcid": "0000-0002-2514-2625" }, { "name": "Peter Kochunov", "orcid": "0000-0003-3656-4281" }, { "name": "Bernd Krämer", "orcid": "0000-0002-1145-9103" }, { "name": "Jun Soo Kwon", "orcid": "0000-0002-1060-1462" }, { "name": "Irina Lebedeva" }, { "name": "Maria Lee", "orcid": "0000-0003-4080-4030" }, { "name": "Rebekka Lencer" }, { "name": "Tiago R. Marques", "orcid": "0000-0003-0602-7661" }, { "name": "Susanne Meinert", "orcid": "0000-0003-2177-7161" }, { "name": "Robin Murray", "orcid": "0000-0003-0829-0519" } ], "bibtex": "https://research.draconitic.com/paper/1gsfha8yccy5j.bib", "cited_by": 0, "doi": "10.64898/2026.10.22.26363656", "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1.full", "id": "1gsfha8yccy5j", "issns": [], "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Article" ], [ "medrxiv", "psychiatry and clinical psychology" ], [ "openalex", "2738|Schizophrenia research and treatment" ] ], "openalex": "W7223664264", "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1.full.pdf", "pmcid": "PMC13734055", "pmid": "42990528", "published": "2026-10-22", "publisher": "Cold Spring Harbor Laboratory Preprints", "ris": "https://research.draconitic.com/paper/1gsfha8yccy5j.ris", "sources": [ { "first_seen": "2026-10-30T12:21:50Z", "native_id": "10.64898/2026.10.22.26363656", "source": "medrxiv", "url": "https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1" }, { "first_seen": "2026-11-08T12:23:42Z", "native_id": "PMC13734055", "source": "pmc", "url": "https://doi.org/10.64898/2026.10.22.26363656" } ], "subjects": [ { "field": "medicine", "origin": "medrxiv:psychiatry and clinical psychology", "subfield": "psychiatry" } ], "title": "Structural brain network organization and aggressive behavior in schizophrenia: a mega-analysis of 2260 patients and 3058 healthy controls from the ENIGMA-Schizophrenia Working Group", "title_text": "Structural brain network organization and aggressive behavior in schizophrenia: a mega-analysis of 2260 patients and 3058 healthy controls from the ENIGMA-Schizophrenia Working Group", "type": "preprint", "updated_at": "2026-11-08T12:23:42Z", "url": "https://research.draconitic.com/paper/1gsfha8yccy5j", "venue": "medRxiv", "versions": [] }