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

Title: Structural brain abnormalities and aggression in schizophrenia:mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium
Authors: Lamsma, Jelle; Raine,Adrian; Kia, Seyed M; Cahn, Wiepke; Arold,Dominic; Banaj,Nerisa; Barone,Annarita; Brosch,Katharina; Brouwer, Rachel; Brunetti,Arturo; Calhoun,Vince D; Chew,Qian H; Choi,Sunah; Chung,Young-Chul; Ciccarelli,Mariateresa; Cobia,Derin; Cocozza,Sirio; Dannlowski,Udo; Dazzan,Paola; de Bartolomeis,Andrea; Di Forti,Marta; Dumais,Alexandre; Edmond,Jesse T; Ehrlich,Stefan; Evermann,Ulrika; Flinkenflügel,Kira; Georgiadis,Foivos; Glahn,David C; Goltermann,Janik; Green,Melissa J; Grotegerd,Dominik; Guerrero-Pedraza,Amalia; Ha,Minji; Hong,Elliot L; Hulshoff Pol, Hilleke; Iasevoli,Felice; Kaiser,Stefan; Kaleda,Vasily; Karuk,Andriana; Kim,Minah; Kircher,Tilo; Kirschner,Matthias; Kochunov,Peter; Kwon,Jun Soo; Lebedeva,Irina; Lencer,Rebekka; Marques,Tiago R; Meinert,Susanne; Murray,Robin; Nenadić,Igor; Nguyen,Dana; Pearlson,Godfrey; Piras,Fabrizio; Pomarol-Clotet,Edith; Pontillo,Giuseppe; Potvin,Stéphane; Preda,Adrian; Quidé,Yann; Rodrigue,Amanda; Rootes-Murdy,Kelly; Salvador,Raymond; Sim,Kang; Skoch,Antonin; Spalletta,Gianfranco; Spaniel,Filip; Stein,Frederike; Thomas-Odenthal,Florian; Tikàsz,Andràs; Tomecek,David; Tomyshev,Alexander; Tranfa,Mario; Tsogt,Uyanga; Turner,Jessica A; van Erp,Theo G M; van Haren, Neeltje E M; van Os, Jim; Vecchio,Daniela; Wang,Lei; Wroblewski,Adrian; Nickl-Jockschat,Thomas; Affectieve & Psychotische Med.; Onderzoeksgroep 1; Onderzoek; Brain; Hersenen-Medisch 1
Publication Year: 2026
Subject Terms: Taverne; Journal Article
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 1359-4184
Relation: https://dspace.library.uu.nl/handle/1874/483593
Availability: https://dspace.library.uu.nl/handle/1874/483593
Rights: info:eu-repo/semantics/EmbargoedAccess
Accession Number: edsbas.558CA055
Database: BASE