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An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium

Published online by Cambridge University Press:  16 October 2019

Ting Yat Wong*
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen, RWTH Aachen University, Aachen, Germany Department of Psychiatry, Brain and Behavioral Laboratory, University of Pennsylvania, Philadelphia, PA, USA
Ruben C. Gur
Department of Psychiatry, Brain and Behavioral Laboratory, University of Pennsylvania, Philadelphia, PA, USA
Thomas Nickl-Jockschat
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen, RWTH Aachen University, Aachen, Germany Department of Psychiatry, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Author for correspondence: Ting Yat Wong, E-mail:,



Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.


To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.


The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.


These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

Original Articles
Copyright © Cambridge University Press 2019

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See the Appendix for additional affiliations of authors, grouped by each research site. For more details regarding the ENIGMA Schizophrenia Working Group (ENIGMA-SZ), see


Affiliation information for all authors can be found in the appendix at the end of the article.


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