Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Autism Spectrum Disorder(University of Toronto), Bipolar Disorder(University of Toronto), Major Depressive Disorder(Hospital for Sick Children), Obsessive-Compulsive Disorder(Centre for Addiction and Mental Health), and Schizophrenia ENIGMA Working Groups(Centre for Addiction and Mental Health), Yash Patel(University of Southern California), Nadine Parker(University of Toronto), Jean Shin(Hospital for Sick Children), Derek Howard(Centre for Addiction and Mental Health), Leon French(Centre for Addiction and Mental Health), Sophia I. Thomopoulos(University of Southern California), Elena Pozzi(University Medical Center Groningen), Yoshinari Abe(Hospital General Universitario Gregorio Marañón), Christoph Abé(Karolinska Institutet), Alan Anticevic(Centre for Addiction and Mental Health), Martin Alda(Dalhousie University), André Alemán(University Medical Center Groningen), Clara Alloza(Hospital General Universitario Gregorio Marañón), Sílvia Alonso-Lana(University of Calgary), Stephanie H. Ameis(Centre for Addiction and Mental Health), Evdokia Anagnostou(University of Toronto), Andrew A. McIntosh(Centre National de la Recherche Scientifique), Celso Arango(Universidad de Cantabria), Paul D. Arnold(University of Calgary), Philip Asherson(King's College London), Francesca Assogna(Heidelberg University), Guillaume Auzias(Centre National de la Recherche Scientifique), Rosa Ayesa‐Arriola(Universidad de Cantabria), Geor Bakker(Maastricht University), Nerisa Banaj(Universidade Federal do Rio Grande do Sul), Tobias Banaschewski(Heidelberg University), Cibele Edom Bandeira(Universidade Federal do Rio Grande do Sul), Baranov Aa(Monash University), Núria Bargalló(IRCCS Ospedale San Raffaele), Claiton H.D. Bau(Universidade Federal do Rio Grande do Sul), Sarah Baumeister(Heidelberg University), Bernhard T. Baune(University of Münster), Mark A. Bellgrove(IRCCS Ospedale San Raffaele), Francesco Benedetti(Centro de Investigación Biomédica en Red de Salud Mental), Alessandro Bertolino(University of Münster), Premika S.W. Boedhoe(University of Basel), Marco P. Boks(Heidelberg University), Irene Bollettini(Harvard University), Caterina del Mar Bonnín(UNSW Sydney), Tiana Borgers(University of Münster), Stefan Borgwardt(University of Basel), Daniel Brandeis(University of Pisa), Brian P. Brennan(Georgia Institute of Technology), Jason Bruggemann(UNSW Sydney), Robin Bülow(Universitätsmedizin Greifswald), Geraldo F. Busatto(Ollscoil na Gaillimhe – University of Galway), Sara Calderoni(University of Pisa), Vince D. Calhoun(Georgia Institute of Technology), Rosa Calvo(Brighton and Sussex Medical School), Erick J. Canales‐Rodríguez(Centro de Investigación Biomédica en Red de Salud Mental), Dara M. Cannon(Ollscoil na Gaillimhe – University of Galway), Vaughan J. Carr(The University of Melbourne), Nicola G. Cascella(Johns Hopkins University), Mara Cercignani(Brighton and Sussex Medical School), Tiffany Chaim-Avancini(King's College London), Anastasia Christakou(University of Minnesota), David Coghill(Universidade Federal do Rio Grande do Sul), Annette Conzelmann(King's College London), Benedicto Crespo‐Facorro(Universidad de Cantabria), Ana I. Cubillo(King's College London), Kathryn R. Cullen(University of Minnesota), Renata B. Cupertino(Centre National de la Recherche Scientifique), Eileen Daly(King's College London), Udo Dannlowski(Centre for Addiction and Mental Health), Christopher G. Davey(City, University of London), Damiaan Denys(University of Münster), Christine Deruelle(Centre National de la Recherche Scientifique), Annabella Di Giorgio(Albert Einstein College of Medicine), Erin W. Dickie(Centre for Addiction and Mental Health), Danai Dima(City, University of London), Katharina Dohm(Oregon Health & Science University), Stefan Ehrlich(Technische Universität Dresden), Benjamin A. Ely(Albert Einstein College of Medicine), Tracy Erwin-Grabner(Centro de Investigación Biomédica en Red de Salud Mental), Thomas Ethofer(University of Pittsburgh), Damien A. Fair(Oregon Health & Science University), Andreas J. Fallgatter(San Francisco VA Medical Center), Stephen V. Faraone(SUNY Upstate Medical University), Mar Fatjó‐Vilas(University of East London), Jennifer Fedor(University of Pittsburgh), Kate D. Fitzgerald(Brighton and Sussex Medical School), Judith M. Ford(Boston Children's Hospital), Thomas Frodl(Trinity College Dublin), Cynthia H.Y. Fu(University of East London), Janice M. Fullerton(Centro de Investigación Biomédica en Red de Salud Mental), Matt C. Gabel(Brighton and Sussex Medical School), David C. Glahn(Boston Children's Hospital), Gloria Roberts(Universitätsmedizin Greifswald), Tinatin Yu. Gogberashvili(Central Clinical Hospital and Polyclinic), José Manuel Goikolea(Universidade Federal do Rio Grande do Sul), Ian H. Gotlib(University of Cape Town), Roberto Goya‐Maldonado(University of Münster), Hans J. Grabe(Heidelberg University), Melissa J. Green(UNSW Sydney), Eugênio H. Grevet(Universidade Federal do Rio Grande do Sul), Nynke A. Groenewold(University of Cape Town), Dominik Grotegerd(University of Münster), Oliver Gruber(Heidelberg University), Patricia Gruner(University Medical Center Groningen), Amalia Guerrero‐Pedraza(Fidmag Sisters Hospitallers), Raquel E. Gur(University of Münster), Ruben C. Gur(Dalhousie University), Shlomi Haar(The University of Melbourne), Bartholomeus C. M. Haarman(Brighton and Sussex Medical School), Jan Haavik(University Medical Center Groningen), Tim Hahn(University of Münster), Tomáš Hájek(Dalhousie University), Ben J. Harrison(The University of Melbourne), Neil A. Harrison(Brighton and Sussex Medical School), Catharina A. Hartman(University Medical Center Groningen), Heather C. Whalley(University of California, San Francisco), Dirk J. Heslenfeld(University Medical Center Groningen), Derrek P. Hibar(Radboud University Nijmegen), Eva Hilland(University of Oslo), Yoshiyuki Hirano(University of Maryland, Baltimore), Tiffany C. Ho(University of California, San Francisco), Pieter J. Hoekstra(University Medical Center Groningen), Liesbeth Hoekstra(Radboud University Nijmegen), Sarah Hohmann(Philipps University of Marburg), L. E. Hong(University of Maryland, Baltimore), Cyril Höschl(University of Oxford), Marie F. Høvik(Hospital General Universitario Gregorio Marañón), Fleur M. Howells(University of British Columbia), Igor Nenadić(Philipps University of Marburg), Maria Jalbrzikowski(University of Pittsburgh), Anthony James(University of Oxford), Joost Janssen(Hospital General Universitario Gregorio Marañón), Fern Jaspers‐Fayer(University of British Columbia), Jian Xu(Montreal Neurological Institute and Hospital), Rune Jonassen(University of Oslo), Georgii Karkashadze(University of Maryland, Baltimore), Joseph A. King(Technische Universität Dresden), Tilo Kircher(Philipps University of Marburg), Matthias Kirschner(Montreal Neurological Institute and Hospital), Kathrin Koch(University of Bonn), Peter Kochunov(University of Maryland, Baltimore), Gregor Kohls(Seoul National University), Kerstin Konrad(Karolinska Institutet), Bernd Krämer(University of Oslo), Axel Krug(University of Bonn), Jonna Kuntsi(King's College London), Jun Soo Kwon(Seoul National University), Mikael Landén(Karolinska Institutet), Nils Inge Landrø(University of Oslo), Luisa Lázaro(South African Medical Research Council), И. С. Лебедева(Universidade de São Paulo), Elisabeth J. Leehr(University of Pittsburgh), Sara Lera‐Miguel(Hospital Clínic de Barcelona), Klaus‐Peter Lesch(University of Calgary), Christine Löchner(South African Medical Research Council), Mário R. Louzã(Universidade de São Paulo), Beatríz Luna(University of Pittsburgh), Astri J. Lundervold(University of Bergen), Frank P. MacMaster(University of Calgary), Luigi A. Maglanoc(University of Oslo), Charles B. Malpas(University of California, San Francisco), Marı́a J. Portella(Trinity College Dublin), Rachel Marsh(Ollscoil na Gaillimhe – University of Galway), Fiona M. Martyn(Ollscoil na Gaillimhe – University of Galway), David Mataix‐Cols(University of Münster), Daniel H. Mathalon(University of California, San Francisco), Hazel McCarthy(Trinity College Dublin), Colm McDonald(Ollscoil na Gaillimhe – University of Galway), Genevieve McPhilemy(Ollscoil na Gaillimhe – University of Galway), Susanne Meinert(University of Münster), José M. Menchón(University of Pisa), Luciano Minuzzi(King's College London), Philip B. Mitchell(King's College London), Carmen Moreno(Hospital General Universitario Gregorio Marañón), Pedro Morgado(Ollscoil na Gaillimhe – University of Galway), Filippo Muratori(University of Pisa), Clodagh M. Murphy(King's College London), Declan Murphy(King's College London), Benson Mwangi(National Institute of Mental Health and Neurosciences), Leila Nabulsi(University of Southern California), Akiko Nakagawa(University of California, Irvine), Takashi Nakamae(Kyoto Prefectural University of Medicine), Leyla S. Namazova-Baranova(University Children's Hospital Zurich), Janardhanan C. Narayanaswamy(Wake Forest University), Neda Jahanshad(University of Southern California), Danai D. Nguyen(University of California, Irvine), Rosa Nicolau(University of California, Los Angeles), Ruth Tuura(Utrecht University), Kirsten O’Hearn(Centro de Investigación Biomédica en Red de Salud Mental), Jaap Oosterlaan(Emma Kinderziekenhuis), Nils Opel(King's College London), Roel A. Ophoff(University of California, Los Angeles), Bob Oranje(Utrecht University), Víctor Ortiz‐García de la Foz(University of Würzburg), Bronwyn J. Overs(Neuroscience Research Australia), Yannis Paloyelis(Universidade Federal do Rio Grande do Sul), Christos Pantelis(The University of Melbourne), Mara Parellada(Hospital General Universitario Gregorio Marañón), Paul Pauli(University of Würzburg), Maria Picó‐Pérez(Centro de Investigación Biomédica en Red de Salud Mental), Felipe Almeida Picon(Universidade Federal do Rio Grande do Sul), Fabrizio Piras(Centro de Investigación Biomédica en Red de Salud Mental), Federica Piras(UNSW Sydney), Kerstin Jessica Plessen(Mental Health Services), Edith Pomarol‐Clotet(Universitat Autònoma de Barcelona), Adrian Preda(University of California, Irvine), Olga Puig(Heidelberg University), Yann Quidé(UNSW Sydney), Joaquim Raduà(University of Münster), Josep Antoni Ramos‐Quiroga(Goethe University Frankfurt), Paul E. Rasser(Amsterdam University Medical Centers), Lisa Rauer(Heidelberg University), Janardhan Reddy(Istituto Nazionale di Fisica Nucleare), Ronny Redlich(Universitat Autònoma de Barcelona), Andreas Reif(Goethe University Frankfurt), Liesbeth Reneman(Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), Jonathan Repple(King's College London), Alessandra Retico(Istituto Nazionale di Fisica Nucleare), Vanesa Richarte(Universitat Autònoma de Barcelona), Anja Richter(Heidelberg University), Pedro G. P. Rosa(Hospital General Universitario Gregorio Marañón), Katya Rubia(King's College London), Ryota Hashimoto(Centro de Investigación Biomédica en Red de Salud Mental), Matthew D. Sacchet(Harvard University), Raymond Salvador(Johns Hopkins University), Javier Santonja(Hospital General Universitario Gregorio Marañón), Kelvin Sarink(University of Münster), Salvador Sarró(Centro de Investigación Biomédica en Red de Salud Mental), Theodore D. Satterthwaite(Universitätsklinikum Aachen), Akira Sawa(Johns Hopkins University), Ulrich Schall(Universidad de Cantabria), Peter R. Schofield(National Human Genome Research Institute), Anouk Schrantee(Utrecht University), Jochen Seitz(Deakin University), Maurício H. Serpa(Institute of Mental Health), Esther Setién‐Suero(Universidad de Cantabria), Philip E. Shaw(Columbia University Irving Medical Center), Devon Shook(Utrecht University), Timothy J. Silk(Deakin University), Kang Sim(Norwegian University of Science and Technology), Schmitt Simon(Philipps University of Marburg), Blair Simpson(Columbia University Irving Medical Center), Aditya Singh(Bellvitge University Hospital), Antonín Škoch(Fondazione Santa Lucia), Norbert Skokauskas(Norwegian University of Science and Technology), Jair C. Soares(Royal Edinburgh Hospital), Noam Soreni(Nathan Kline Institute for Psychiatric Research), Carles Soriano‐Mas(University of British Columbia), Gianfranco Spalletta(Fondazione Santa Lucia), Filip Španiel(University of Cape Town), Stephen M. Lawrie(Royal Edinburgh Hospital), Emily Stern(Nathan Kline Institute for Psychiatric Research), S. Evelyn Stewart(University of British Columbia), Yoichiro Takayanagi(Fondazione Stella Maris), Henk Temmingh(University of Cape Town), David F. Tolin(Maastricht University), David Tomeček(Leiden University Medical Center), Diana Tordesillas‐Gutiérrez(Leiden University Medical Center), Michela Tosetti(Fondazione Stella Maris), Anne Uhlmann(University of Cape Town), Thérèse van Amelsvoort(Royal Children's Hospital), Nic J. A. van der Wee(Universidad de Cantabria), Steven J.A. van der Werff(Leiden University Medical Center), Neeltje E. M. van Haren(National Institute of Mental Health and Neurosciences), Guido van Wingen(Centro de Investigación Biomédica en Red de Salud Mental), Alasdair Vance(Universitat Autònoma de Barcelona), Javier Vázquez-Bourgón(Universidad de Cantabria), Daniela Vecchio(Centre for Addiction and Mental Health), Ganesan Venkatasubramanian(Universitätsmedizin Greifswald), Eduard Vieta(Centro de Investigación Biomédica en Red de Salud Mental), Óscar Vilarroya(Universitat Autònoma de Barcelona), Yolanda Vives‐Gilabert(UNSW Sydney), Aristotle N. Voineskos(Centre for Addiction and Mental Health), Henry Völzke(University of California, Irvine), Georg G. von Polier(German Center for Neurodegenerative Diseases), Esther Walton(University of Bath), Thomas W. Weickert(UNSW Sydney), Cynthia Shannon Weickert(University of California, San Francisco), Andrea Weideman(Johns Hopkins University), Katharina Wittfeld(German Center for Neurodegenerative Diseases), Daniel H. Wolf(Seoul National University Hospital), Mon-Ju Wu(Kunming Medical University), Tony T. Yang(University of California, San Francisco), Kun Yang(Johns Hopkins University), Yuliya Yoncheva(Radboud University Nijmegen), Je‐Yeon Yun(Radboud University Nijmegen), Yuqi Cheng(Radboud University Nijmegen), Marcus V. Zanetti(Radboud University Nijmegen), Georg Ziegler(University of Oslo), Barbara Franke(University of Southern California), Martine Hoogman(Radboud University Nijmegen), Jan K. Buitelaar(Radboud University Nijmegen), Daan van Rooij(South African Medical Research Council), Ole A. Andreassen(University of Oslo), Christopher R. K. Ching(University of Southern California), Dick J. Veltman(University of California, Irvine), Lianne Schmaal(The University of Melbourne), Dan J. Stein(South African Medical Research Council), Odile A. van den Heuvel(University of Toronto), Jessica A. Turner(Georgia State University), Theo G.M. van Erp(University of California, Irvine), Zdenka Pausová(Hospital for Sick Children), Paul M. Thompson(University of Southern California), Tomáš Paus(University of Toronto)
Cited by 262Open Access
Abstract
IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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