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

Jelle Lamsma, Adrian Raine, Seyed M Kia, Wiepke Cahn, Dominic Arold, Nerisa Banaj, Annarita Barone, Katharina Brosch, Rachel Brouwer, Arturo Brunetti, Vince D Calhoun, Qian H Chew, Sunah Choi, Young-Chul Chung, Mariateresa Ciccarelli, Derin Cobia, Sirio Cocozza, Udo Dannlowski, Paola Dazzan, Andrea de BartolomeisMarta Di Forti, Alexandre Dumais, Jesse T Edmond, Stefan Ehrlich, Ulrika Evermann, Kira Flinkenflügel, Foivos Georgiadis, David C Glahn, Janik Goltermann, Melissa J Green, Dominik Grotegerd, Amalia Guerrero-Pedraza, Minji Ha, Elliot L Hong, Hilleke Hulshoff Pol, Felice Iasevoli, Stefan Kaiser, Vasily Kaleda, Andriana Karuk, Minah Kim, Tilo Kircher, Matthias Kirschner, Peter Kochunov, Jun Soo Kwon, Irina Lebedeva, Rebekka Lencer, Tiago R Marques, Susanne Meinert, Robin Murray, Igor Nenadić, Dana Nguyen, Godfrey Pearlson, Fabrizio Piras, Edith Pomarol-Clotet, Giuseppe Pontillo, Stéphane Potvin, Adrian Preda, Yann Quidé, Amanda Rodrigue, Kelly Rootes-Murdy, Raymond Salvador, Antonin Skoch, Kang Sim, Gianfranco Spalletta, Filip Spaniel, Frederike Stein, Florian Thomas-Odenthal, Andràs Tikàsz, David Tomecek, Alexander Tomyshev, Mario Tranfa, Uyanga Tsogt, Jessica A Turner, Theo G M van Erp, Neeltje E M van Haren, Jim van Os, Daniela Vecchio, Lei Wang, Adrian Wroblewski, Thomas Nickl-Jockschat

Research output: Contribution to journalArticleScientific

Abstract

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome.

METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z -scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale.

RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10 -5 ) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.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 ). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control.

CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Original languageEnglish
JournalMedRxiv
DOIs
Publication statusUnpublished - 5 Feb 2024

Fingerprint

Dive into the research topics of 'Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium'. Together they form a unique fingerprint.

Cite this