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
Year: 2026
Type: preprint
Abstract: Background Although 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. Methods We 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, Δ K = 0.01). Group differences were assessed using pairwise permutation tests with Benjamini–Hochberg correction for multiple comparisons. Results Global 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 (ΔAUC = 0.018, p BH = .083). In exploratory subgroup analyses, higher SN network–rest density was observed only in SZ+A with high delusion severity (ΔAUC = 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. Conclusions SZ+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.
Source: medRxiv
Authors: Jelle Lamsma, Paolo Fusar-Poli, Martijn van den Heuvel, Derin Cobia, Adrian Raine, Bin Wan, Matthias Kirschner, Wiepke Cahn, Dominic Arold, Mihai Avram, Nerisa Banaj, Annarita Barone, Stefan Borgwardt, Katharina Brosch, Rachel M. Brouwer, Arturo Brunetti, Vince D. Calhoun, Sean Carruthers, Giacomo Cecere, Simon Cervenka, Qian H. Chew, Sunah Choi, Young-Chul Chung, Mariateresa Ciccarelli, Sirio Cocozza, Benedicto Crespo-Facorro, Udo Dannlowski, Paola Dazzan, Andrea de Bartolomeis, Marta Di Forti, Stefan Ehrlich, Simone Elia, Asia Ferrari, Marc Fischer, Kira Flinkenflügel, David C. Glahn, Janik Goltermann, Melissa J. Green, Dominik Grotegerd, Oliver Gruber, Amalia Guerrero-Pedraza, Minji Ha, Philipp Homan, L. Elliot Hong, Matthew Hughes, Felice Iasevoli, Stefan Kaiser, Vasily Kaleda, Andriana Karuk, Minah Kim, Tilo Kircher, Peter Kochunov, Bernd Krämer, Jun Soo Kwon, Irina Lebedeva, Maria Lee, Rebekka Lencer, Tiago R. Marques, Susanne Meinert, Robin Murray, Igor Nenadić, Dana Nguyen, Soyolsaikhan Odkhuu, Wolfgang Omlor, Godfrey Pearlson, Rosanne Picotin, Fabrizio Piras, Edith Pomarol-Clotet, Giuseppe Pontillo, Adrian Preda, Rafael Romero-Garcia, Yann Quidé, Elysha Ringin, Amanda Rodrigue, Kelly Rootes-Murdy, Susan L. Rossell, Raymond Salvador, Freda Scheffler, Patricia Segura, Carl M. Sellgren, Kang Sim, Antonin Skoch, Filip Spaniel, Frederike Stein, Philip J. Sumner, Henk Temmingh, Florian Thomas-Odenthal, David Tomecek, Alexander Tomyshev, Mario Tranfa, Jessica A. Turner, Theo G. M. van Erp, Neeltje van Haren, Tamsyn E. Van Rheenen, Jim van Os, Daniela Vecchio, Lei Wang, Will Woods, Thomas Nickl-Jockschat
Institutions: King's College London, University Medical Center Utrecht, Vrije Universiteit Amsterdam, Brigham Young University, University of Pennsylvania, University of Geneva, Forschungszentrum Jülich, University Hospital of Geneva, Max Planck Institute for Human Cognitive and Brain Sciences, University of Zurich, Technische Universität Dresden, University of Lübeck, Fondazione Santa Lucia, Istituti di Ricovero e Cura a Carattere Scientifico, University of Naples Federico II, Northwell Health, Feinstein Institute for Medical Research, Philipps University of Marburg, Georgia Institute of Technology, Emory University, Georgia State University, Center for Translational Research in Neuroimaging and Data Science, Swinburne University of Technology, Psychiatrische Universitätsklinik Zürich, Uppsala University, Region Stockholm, Karolinska Institutet, Stockholm Health Care Services, Institute of Mental Health, Seoul National University, Jeonbuk National University Hospital, Jeonbuk National University, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Bielefeld University, University of Münster, Deutsches Zentrum für Psychische Gesundheit, Heidelberg University, Boston Children's Hospital, Harvard University, UNSW Sydney, ETH Zurich, The University of Texas Health Science Center at Houston, Mental Health Research Center of Russian Academy of Medical Sciences, Fidmag Sisters Hospitallers, Seoul National University Hospital, MRC London Institute of Medical Sciences, Imperial College London, University of California, Irvine, Neuroscience Research Australia, The University of Melbourne, Atlanta VA Medical Center, University of Cape Town, National Institute of Mental Health, Czech Academy of Sciences, Czech Academy of Sciences, Institute of Computer Science, Czech Technical University in Prague, The Ohio State University Wexner Medical Center, The Ohio State University, Erasmus MC, Erasmus MC - Sophia Children’s Hospital, Maastricht University Medical Centre, Maastricht University, Northwestern University, University of Iowa, Otto-von-Guericke-Universität Magdeburg
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223664264