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

@misc{lamsma2026structural,
  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}},
  author = {Jelle Lamsma and Paolo Fusar-Poli and Martijn van den Heuvel and Derin Cobia and Adrian Raine and Bin Wan and Matthias Kirschner and Wiepke Cahn and Dominic Arold and Mihai Avram and Nerisa Banaj and Annarita Barone and Stefan Borgwardt and Katharina Brosch and Rachel M. Brouwer and Arturo Brunetti and Vince D. Calhoun and Sean Carruthers and Giacomo Cecere and Simon Cervenka and Qian H. Chew and Sunah Choi and Young-Chul Chung and Mariateresa Ciccarelli and Sirio Cocozza and Benedicto Crespo-Facorro and Udo Dannlowski and Paola Dazzan and Andrea de Bartolomeis and Marta Di Forti and Stefan Ehrlich and Simone Elia and Asia Ferrari and Marc Fischer and Kira Flinkenflügel and David C. Glahn and Janik Goltermann and Melissa J. Green and Dominik Grotegerd and Oliver Gruber and Amalia Guerrero-Pedraza and Minji Ha and Philipp Homan and L. Elliot Hong and Matthew Hughes and Felice Iasevoli and Stefan Kaiser and Vasily Kaleda and Andriana Karuk and Minah Kim and Tilo Kircher and Peter Kochunov and Bernd Krämer and Jun Soo Kwon and Irina Lebedeva and Maria Lee and Rebekka Lencer and Tiago R. Marques and Susanne Meinert and Robin Murray},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.22.26363656},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1},
  note = {CC BY},
}

TY  - UNPB
TI  - 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
AU  - Jelle Lamsma
AU  - Paolo Fusar-Poli
AU  - Martijn van den Heuvel
AU  - Derin Cobia
AU  - Adrian Raine
AU  - Bin Wan
AU  - Matthias Kirschner
AU  - Wiepke Cahn
AU  - Dominic Arold
AU  - Mihai Avram
AU  - Nerisa Banaj
AU  - Annarita Barone
AU  - Stefan Borgwardt
AU  - Katharina Brosch
AU  - Rachel M. Brouwer
AU  - Arturo Brunetti
AU  - Vince D. Calhoun
AU  - Sean Carruthers
AU  - Giacomo Cecere
AU  - Simon Cervenka
AU  - Qian H. Chew
AU  - Sunah Choi
AU  - Young-Chul Chung
AU  - Mariateresa Ciccarelli
AU  - Sirio Cocozza
AU  - Benedicto Crespo-Facorro
AU  - Udo Dannlowski
AU  - Paola Dazzan
AU  - Andrea de Bartolomeis
AU  - Marta Di Forti
AU  - Stefan Ehrlich
AU  - Simone Elia
AU  - Asia Ferrari
AU  - Marc Fischer
AU  - Kira Flinkenflügel
AU  - David C. Glahn
AU  - Janik Goltermann
AU  - Melissa J. Green
AU  - Dominik Grotegerd
AU  - Oliver Gruber
AU  - Amalia Guerrero-Pedraza
AU  - Minji Ha
AU  - Philipp Homan
AU  - L. Elliot Hong
AU  - Matthew Hughes
AU  - Felice Iasevoli
AU  - Stefan Kaiser
AU  - Vasily Kaleda
AU  - Andriana Karuk
AU  - Minah Kim
AU  - Tilo Kircher
AU  - Peter Kochunov
AU  - Bernd Krämer
AU  - Jun Soo Kwon
AU  - Irina Lebedeva
AU  - Maria Lee
AU  - Rebekka Lencer
AU  - Tiago R. Marques
AU  - Susanne Meinert
AU  - Robin Murray
PY  - 2026
DA  - 2026/10/22
PB  - medRxiv
DO  - 10.64898/2026.10.22.26363656
UR  - https://www.medrxiv.org/content/10.64898/2026.10.22.26363656v1
AB  - 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.  MethodsWe 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.  ResultsGlobal 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.  ConclusionsSZ+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.
ER  -