Structural brain abnormalities and aggression in schizophrenia: mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium.
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.
Authors
Lamsma Lamsma, Raine Raine, Kia Kia, Cahn Cahn, Arold Arold, Banaj Banaj, Barone Barone, Brosch Brosch, Brouwer Brouwer, Brunetti Brunetti, Calhoun Calhoun, Chew Chew, Choi Choi, Chung Chung, Ciccarelli Ciccarelli, Cobia Cobia, Cocozza Cocozza, Dannlowski Dannlowski, Dazzan Dazzan, de Bartolomeis de Bartolomeis, Di Forti Di Forti, Dumais Dumais, Edmond Edmond, Ehrlich Ehrlich, Evermann Evermann, Flinkenflügel Flinkenflügel, Georgiadis Georgiadis, Glahn Glahn, Goltermann Goltermann, Green Green, Grotegerd Grotegerd, Guerrero-Pedraza Guerrero-Pedraza, Ha Ha, Hong Hong, Hulshoff Pol Hulshoff Pol, Iasevoli Iasevoli, Kaiser Kaiser, Kaleda Kaleda, Karuk Karuk, Kim Kim, Kircher Kircher, Kirschner Kirschner, Kochunov Kochunov, Kwon Kwon, Lebedeva Lebedeva, Lencer Lencer, Marques Marques, Meinert Meinert, Murray Murray, Nenadić Nenadić, Nguyen Nguyen, Pearlson Pearlson, Piras Piras, Pomarol-Clotet Pomarol-Clotet, Pontillo Pontillo, Potvin Potvin, Preda Preda, Quidé Quidé, Rodrigue Rodrigue, Rootes-Murdy Rootes-Murdy, Salvador Salvador, Sim Sim, Skoch Skoch, Spalletta Spalletta, Spaniel Spaniel, Stein Stein, Thomas-Odenthal Thomas-Odenthal, Tikàsz Tikàsz, Tomecek Tomecek, Tomyshev Tomyshev, Tranfa Tranfa, Tsogt Tsogt, Turner Turner, van Erp van Erp, van Haren van Haren, van Os van Os, Vecchio Vecchio, Wang Wang, Wroblewski Wroblewski, Nickl-Jockschat Nickl-Jockschat
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