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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

  • T.Y. Wong
  • , J. Radua
  • , E. Pomarol-Clotet
  • , R. Salvador
  • , A. Albajes-Eizagirre
  • , A. Solanes
  • , E.J. Canales-Rodriguez
  • , A. Guerrero-Pedraza
  • , S. Sarro
  • , T. Kircher
  • , I. Nenadic
  • , A. Krug
  • , D. Grotegerd
  • , U. Dannlowski
  • , S. Borgwardt
  • , A. Riecher-Rössler
  • , A. Schmidt
  • , C. Andreou
  • , C.G. Huber
  • , J. Turner
  • V. Calhoun, W. Jiang, S. Clark, E. Walton, G. Spalletta, N. Banaj, F. Piras, V. Ciullo, D. Vecchio, I. Lebedeva, A.S. Tomyshev, V. Kaleda, T. Klushnik, G.B. Filho, M.V. Zanetti, M.H. Serpa, P.G. Penteado Rosa, R. Hashimoto, M. Fukunaga, A. Richter, B. Krämer, O. Gruber, A.N. Voineskos, E.W. Dickie, D. Tomecek, A. Skoch, F. Spaniel, C. Hoschl, A. Bertolino, A. Bonvino, A. Di Giorgio, L. Holleran, S. Ciufolini, T.R. Marques, P. Dazzan, R. Murray, J. Lamsma, W. Cahn, N. Van Haren, A.M. Diáz-Zuluaga, J.A. Pineda-Zapata, C. Vargas, C. López-Jaramillo, T.G.M. Van Erp, R.C. Gur, T. Nickl-Jockschat

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Copyright © Cambridge University Press 2019.Background 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.Method 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.Results 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.Conclusion 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 languageEnglish
Pages (from-to)2034-2045
JournalPsychological Medicine
Volume50
Issue number12
DOIs
Publication statusPublished - 1 Sept 2020
Externally publishedYes

Funding

Joaquim Radua1,2,3,4,5, Edith Pomarol-Clotet1,2, Raymond Salvador1,2, Anton Albajes-Eizagirre1,2, Aleix Solanes1,3, Erick J. Canales-Rodriguez1,2,6,7, Amalia Guerrero-Pedraza8 and Salvador Sarro1,2 1FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain 2Mental Health Research Networking Center (CIBERSAM), Madrid, Spain 3Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 4Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK 5Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 6Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland 7Signal Processing Lab (LTS5), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland 8Benito Menni Complex Assistencial en Salut Mental, Sant Boi de Llobregat, Spain Acknowledgment: This work was supported by the Catalan Government (2017-SGR-1271 to FIDMAG) and several grants from the Plan Nacional de I+D+i 2008–2011 and 2013–2016, and the Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, ‘Investing in your future’): Miguel Servet Research Contracts (MS14/00041 to JR, CPII13/00018 to RS and CPii16/00018 to EP-C) and Research Project Grants (PI14/01151 to RS, PI14/01148 to EP-C, PI14/00292 and CP14/00041 to JR, and PI15/00277 to EC-R). Tilo Kircher1, Igor Nenadic1, Axel Krug1, Dominik Grotegerd2 and Udo Dannlowski2 1University of Marburg, Department of Psychiatry and Psychotherapy, Marburg, Germany 2University of Münster, Department of Psychiatry, Marburg, Germany Acknowledgment: This work was funded by the German Research Foundation (DFG, grant FOR2107 KI 588/14-1, KI 588/14-2, KI 588/17-1 to TK; grant KR 3822/7-1, KR 3822/7-2 to AK, grant NE 2254/1-2 to IN; grant DA1151/5-1, DA1151/5-2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). Stefan Borgwardt1, Anita Riecher-Rössler1, Andre Schmidt1, Christina Andreou1 and Christian Huber1 1Department of Psychiatry (UPK), University of Basel, Basel, Switzerland Acknowledgment: We would like to thank the UPK Forschungsförderungsfonds for grant support. Jessica Turner1, Vince Calhoun2,3, Wenhao Jiang1, Sarah Clark1 and Esther Walton4 1Department of Psychology, Georgia State University, Atlanta, Georgia, USA 2The Mind Research Network, Albuquerque, NM, USA 3Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA 4Department of Psychology, University of Bath, Bath, UK Acknowledgment: The imaging data and phenotypic information were collected and shared by the Mind Research Network and the University of New Mexico funded by a National Institute of Health Center of Biomedical Research Excellence (COBRE) grant 1P20RR021938-01A2. Gianfranco Spalletta1,2, Nerisa Banaj1, Fabrizio Piras1, Valentina Ciullo1,3 and Daniela Vecchio1 1Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy 2Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA 3Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Italy Acknowledgment: This work was supported by the Italian Ministry of Health grants RC 12-13-14-15-16-17-18-19/A. Irina Lebedeva1, Alexander S. Tomyshev1, Vasily Kaleda1 and Tatyana Klushnik1 1Mental Health Research Center, Moscow, Russia Geraldo Busatto Filho1, Marcus Vinicius Zanetti1,2, Mauricio Henriques Serpa1 and Pedro Gomes Penteado Rosa1 1Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil 2Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, Sao Paulo, SP, Brazil Ryota Hashimoto1,2 and Masaki Fukunaga3 1Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan 2Osaka University, Osaka, Japan 3Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan Anja Richter1,2, Bernd Krämer1 and Oliver Gruber1 1Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, University Hospital Heidelberg, 69115 Heidelberg, Germany 2Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK Aristotle N. Voineskos1,2 and Erin W. Dickie1,2 1Addiction and Mental Health, Toronto, Canada 2Department of Psychiatry, University of Toronto, Toronto, Canada Acknowledgment: The CAMH datasets were collected and shared with support from the CAMH Foundation, Canadian Institutes of Health Research, the Ontario Mental Health Foundation and the Brain and Behavior Research Foundation. David Tomecek1,2,3, Antonin Skoch1,4, Filip Spaniel1, Cyril Hoschl1 1National Institute of Mental Health, Klecany, Czech Republic 2Institute of Computer Science, Czech Academy of Sciences, Czech Technical University in Prague, Prague, Czech Republic 3Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic 4MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Acknowledgment: The National Institute of Mental Health, Klecany, Czech Republic was supported by project no. LO1611 with funding from the MEYS under the NPU I program. Alessandro Bertolino1, Aurora Bonvino1 and Annabella Di Giorgio2 1Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Italy 2Section of Clinical Neuroscience, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy Laurena Holleran1 1Neuroimaging and Cognitive Genomics Group, NUI Galway, Ireland Simone Ciufolini1, Tiago Reis Marques1, Paola Dazzan1 and Robin Murray1 1Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK Jelle Lamsma1,2, Wiepke Cahn1,3 and Neeltje van Haren1,4 1Department of Psychiatry, University Medical Centre Utrecht, Utrecht, The Netherlands 2Department of Psychiatry, University of Oxford, Oxford, UK 3Utrecht Mental Health Institute, Utrecht, The Netherlands 4Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands Ana M. Díaz-Zuluaga1, Julián A. Pineda-Zapata2, Cristian Vargas1 and Carlos López-Jaramillo1,3 1Research Group of Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia 2Research Group, Instituto de Alta Tecnología Médica (IATM), Medellín, Antioquia, Colombia 3Mood Disorders Program, Hospital Universitario San Vicente Fundación, Medellín, Colombia Theo G. M. van Erp1,2 1Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA 2Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA 92697, USA Acknowledgement: TGMvE is supported by the ENIGMA’s NIH Big Data to Knowledge (BD2K) initiative U54 EB020403, and the ENIGMA Sex Differences Initiative R01 MH116147. Acknowledgement. ENIGMA was supported in part by a Consortium grant (U54 EB020403) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NIMH. This study is also supported by Deutsche Forschungsgemeinschaft (DFG, International Research Training Group IRTG2150). Acknowledgments for the various participating data contributors are listed in the Appendix.

FundersFunder number
Instituto de Psiquiatria, Hospital das Clinicas
Universidad de Antioquia
Interdisciplinary Center for Clinical Research
King’s College London
IATM
Secretaría de Estado de Investigacion, Desarrollo e Innovacion
Instituto de Salud Carlos III
Universidade de São Paulo
University Hospital Heidelberg
Centre Hospitalier Universitaire Vaudois
Health Research Networking Center
National Institute for Physiological Sciences
National Institute of Mental Health
National Institute of Biomedical Imaging and Bioengineering
National Institute of Health Center of Biomedical Research Excellence
Menninger Department of Psychiatry and Behavioral Sciences
Akademie Věd České Republiky
IRCCS Santa Lucia Foundation
Brazil 2Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês
Department of Clinical and Behavioral Neurology
Ministry of Education, Youth and Science
Ontario Mental Health Foundation
Department of General Psychiatry
National Institutes of Health
University of New Mexico
Università degli Studi di Firenze
European Commission
Centre for Addiction and Mental Health Foundation
Centro de Investigación Biomédica en Red de Salud Mental
Universität Basel
Karolinska Institutet
École Polytechnique Fédérale de Lausanne
Instituto de Alta Tecnología Médica
Sant Boi de Llobregat
Brain and Behavior Research Foundation
National Center of Neurology and Psychiatry
Canadian Institutes of Health Research
Menni Complex Assistencial en Salut Mental
University of California, Irvine
IZKF
Baylor College of Medicine
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medical faculty of MünsterDan3/012/17
International Research Training GroupIRTG2150
Catalan Government2017-SGR-1271
Deutsche ForschungsgemeinschaftKI 588/17-1, NE 2254/1-2, DA1151/5-2, KI 588/14-2, SFB-TRR58, DA1151/5-1, FOR2107 KI 588/14-1, KR 3822/7-1, KR 3822/7-2
Italian Ministry of HealthLIM-21, RC 12-13-14-15-16-17-18-19
České Vysoké Učení Technické v PrazeLO1611
COBRE1P20RR021938-01A2
University of California IrvineCA 92697, U54 EB020403, R01 MH116147
ERDF/ESFPI14/01148, MS14/00041, CPii16/00018, CPII13/00018, PI15/00277, CP14/00041, PI14/01151, PI14/00292

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