Year: 2020
Type: article
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.
Source: JAMA Psychiatry
Authors: Autism Spectrum Disorder, Bipolar Disorder, Major Depressive Disorder, Obsessive-Compulsive Disorder, and Schizophrenia ENIGMA Working Groups, Yash Patel, Nadine Parker, Jean Shin, Derek Howard, Leon French, Sophia I. Thomopoulos, Elena Pozzi, Yoshinari Abe, Christoph Abé, Alan Anticevic, Martin Alda, Andre Aleman, Clara Alloza, Silvia Alonso-Lana, Stephanie H. Ameis, Evdokia Anagnostou, Andrew A. McIntosh, Celso Arango, Paul D. Arnold, Philip Asherson, Francesca Assogna, Guillaume Auzias, Rosa Ayesa-Arriola, Geor Bakker, Nerisa Banaj, Tobias Banaschewski, Cibele E. Bandeira, Alexandr Baranov, Núria Bargalló, Claiton H. D. Bau, Sarah Baumeister, Bernhard T. Baune, Mark A. Bellgrove, Francesco Benedetti, Alessandro Bertolino, Premika S. W. Boedhoe, Marco Boks, Irene Bollettini, Caterina del Mar Bonnin, Tiana Borgers, Stefan Borgwardt, Daniel Brandeis, Brian P. Brennan, Jason M. Bruggemann, Robin Bülow, Geraldo F. Busatto, Sara Calderoni, Vince D. Calhoun, Rosa Calvo, Erick J. Canales-Rodríguez, Dara M. Cannon, Vaughan J. Carr, Nicola Cascella, Mara Cercignani, Tiffany M. Chaim-Avancini, Anastasia Christakou, David Coghill, Annette Conzelmann, Benedicto Crespo-Facorro, Ana I. Cubillo, Kathryn R. Cullen, Renata B. Cupertino, Eileen Daly, Udo Dannlowski, Christopher G. Davey, Damiaan Denys, Christine Deruelle, Annabella Di Giorgio, Erin W. Dickie, Danai Dima, Katharina Dohm, Stefan Ehrlich, Benjamin A. Ely, Tracy Erwin-Grabner, Thomas Ethofer, Damien A. Fair, Andreas J. Fallgatter, Stephen V. Faraone, Mar Fatjó-Vilas, Jennifer M. Fedor, Kate D. Fitzgerald, Judith M. Ford, Thomas Frodl, Cynthia H. Y. Fu, Janice M. Fullerton, Matt C. Gabel, David C. Glahn, Gloria Roberts, Tinatin Gogberashvili, Jose M. Goikolea, Ian H. Gotlib, Roberto Goya-Maldonado, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Patricia Gruner, Amalia Guerrero-Pedraza, Raquel E. Gur, Ruben C. Gur, Shlomi Haar, Bartholomeus C. M. Haarman, Jan Haavik, Tim Hahn, Tomas Hajek, Benjamin J. Harrison, Neil A. Harrison, Catharina A. Hartman, Heather C. Whalley, Dirk J. Heslenfeld, Derrek P. Hibar, Eva Hilland, Yoshiyuki Hirano, Tiffany C. Ho, Pieter J. Hoekstra, Liesbeth Hoekstra, Sarah Hohmann, L. E. Hong, Cyril Höschl, Marie F. Høvik, Fleur M. Howells, Igor Nenadic, Maria Jalbrzikowski, Anthony C. James, Joost Janssen, Fern Jaspers-Fayer, Jian Xu, Rune Jonassen, Georgii Karkashadze, Joseph A. King, Tilo Kircher, Matthias Kirschner, Kathrin Koch, Peter Kochunov, Gregor Kohls, Kerstin Konrad, Bernd Krämer, Axel Krug, Jonna Kuntsi, Jun Soo Kwon, Mikael Landén, Nils I. Landrø, Luisa Lazaro, Irina S. Lebedeva, Elisabeth J. Leehr, Sara Lera-Miguel, Klaus-Peter Lesch, Christine Lochner, Mario R. Louza, Beatriz Luna, Astri J. Lundervold, Frank P. MacMaster, Luigi A. Maglanoc, Charles B. Malpas, Maria J. Portella, Rachel Marsh, Fiona M. Martyn, David Mataix-Cols, Daniel H. Mathalon, Hazel McCarthy, Colm McDonald, Genevieve McPhilemy, Susanne Meinert, José M. Menchón, Luciano Minuzzi, Philip B. Mitchell, Carmen Moreno, Pedro Morgado, Filippo Muratori, Clodagh M. Murphy, Declan Murphy, Benson Mwangi, Leila Nabulsi, Akiko Nakagawa, Takashi Nakamae, Leyla Namazova, Janardhanan Narayanaswamy, Neda Jahanshad, Danai D. Nguyen, Rosa Nicolau, Ruth L. O'Gorman Tuura, Kirsten O'Hearn, Jaap Oosterlaan, Nils Opel, Roel A. Ophoff, Bob Oranje, Victor Ortiz García de la Foz, Bronwyn J. Overs, Yannis Paloyelis, Christos Pantelis, Mara Parellada, Paul Pauli, Maria Picó-Pérez, Felipe A. Picon, Fabrizio Piras, Federica Piras, Kerstin J. Plessen, Edith Pomarol-Clotet, Adrian Preda, Olga Puig, Yann Quidé, Joaquim Radua, J. Antoni Ramos-Quiroga, Paul E. Rasser, Lisa Rauer, Janardhan Reddy, Ronny Redlich, Andreas Reif, Liesbeth Reneman, Jonathan Repple, Alessandra Retico, Vanesa Richarte, Anja Richter, Pedro G. P. Rosa, Katya K. Rubia, Ryota Hashimoto, Matthew D. Sacchet, Raymond Salvador, Javier Santonja, Kelvin Sarink, Salvador Sarró, Theodore D. Satterthwaite, Akira Sawa, Ulrich Schall, Peter R. Schofield, Anouk Schrantee, Jochen Seitz, Mauricio H. Serpa, Esther Setién-Suero, Philip Shaw, Devon Shook, Tim J. Silk, Kang Sim, Schmitt Simon, Helen Blair Simpson, Aditya Singh, Antonin Skoch, Norbert Skokauskas, Jair C. Soares, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Filip Spaniel, Stephen M. Lawrie, Emily R. Stern, S. Evelyn Stewart, Yoichiro Takayanagi, Henk S. Temmingh, David F. Tolin, David Tomecek, Diana Tordesillas-Gutiérrez, Michela Tosetti, Anne Uhlmann, Therese van Amelsvoort, Nic J. A. van der Wee, Steven J. A. van der Werff, Neeltje E. M. van Haren, Guido A. van Wingen, Alasdair Vance, Javier Vázquez-Bourgon, Daniela Vecchio, Ganesan Venkatasubramanian, Eduard Vieta, Oscar Vilarroya, Yolanda Vives-Gilabert, Aristotle N. Voineskos, Henry Völzke, Georg G. von Polier, Esther Walton, Thomas W. Weickert, Cynthia Shannon Weickert, Andrea S. Weideman, Katharina Wittfeld, Daniel H. Wolf, Mon-Ju Wu, T. T. Yang, Kun Yang, Yuliya Yoncheva, Je-Yeon Yun, Yuqi Cheng, Marcus V. Zanetti, Georg C. Ziegler, Barbara Franke, Martine Hoogman, Jan K. Buitelaar, Daan van Rooij, Ole A. Andreassen, Christopher R. K. Ching, Dick J. Veltman, Lianne Schmaal, Dan J. Stein, Odile A. van den Heuvel, Jessica A. Turner, Theo G. M. van Erp, Zdenka Pausova, Paul M. Thompson, Tomáš Paus
Institutions: University of Toronto, Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Hospital for Sick Children, Centre for Addiction and Mental Health, University of Southern California, Orygen, Kyoto Prefectural University of Medicine, Karolinska Institutet, Yale University, Dalhousie University, University Medical Center Groningen, University of Groningen, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Fidmag Sisters Hospitallers, Campbell Family Mental Health Research Institute, Royal Edinburgh Hospital, University of Edinburgh, University of Calgary, Hotchkiss Brain Institute, Mathison Centre for Mental Health Research and Education, King's College London, Fondazione Santa Lucia, Centre National de la Recherche Scientifique, Aix-Marseille Université, Institut de Neurosciences de la Timone, Universidad de Cantabria, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Maastricht University, Heidelberg University, Central Institute of Mental Health, Medizinische Fakultät Mannheim, Universidade Federal do Rio Grande do Sul, Russian Academy of Sciences, Central Clinical Hospital and Polyclinic, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, University of Münster, Monash University, IRCCS Ospedale San Raffaele, University of Bari Aldo Moro, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, University Medical Center Utrecht, Universitat de Barcelona, University of Basel, Harvard University, McLean Hospital, UNSW Sydney, Universitätsmedizin Greifswald, Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, University of Pisa, Fondazione Stella Maris, Georgia Institute of Technology, Emory University, Georgia State University, Center for Translational Research in Neuroimaging and Data Science, Hospital Clínic de Barcelona, Ollscoil na Gaillimhe – University of Galway, Johns Hopkins University, Johns Hopkins Medicine, Brighton and Sussex Medical School, University of Sussex, University of Reading, The University of Melbourne, Universitätsklinikum Tübingen, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, University of Zurich, University of Minnesota, Casa Sollievo della Sofferenza, City, University of London, City St George's, University of London, Technische Universität Dresden, Albert Einstein College of Medicine, Universitätsmedizin Göttingen, University of Tübingen, Oregon Health & Science University, SUNY Upstate Medical University, University of Pittsburgh, University of Michigan, Michigan Medicine, San Francisco VA Medical Center, Trinity College Dublin, University of East London, Neuroscience Research Australia, Boston Children's Hospital, Stanford University, University of Cape Town, University Hospital Heidelberg, University of Pennsylvania, Imperial College London, University of Bergen, Melbourne Health, Genentech, University of Oslo, Chiba University, Research Center for Child Mental Development, Chiba University, University of California, San Francisco, Radboud University Nijmegen, Radboud University Medical Center, University of Maryland, Baltimore, National Institute of Mental Health, Philipps University of Marburg, University of Oxford, University of British Columbia, First Affiliated Hospital of Kunming Medical University, Montreal Neurological Institute and Hospital, McGill University, TUM Klinikum, Technical University of Munich, Universitätsklinikum Aachen, RWTH Aachen University, Jülich Aachen Research Alliance, University of Bonn, Seoul National University, Mental Health Research Center of Russian Academy of Medical Sciences, University of Würzburg, Stellenbosch University, Murdoch Children's Research Institute, Columbia University, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, McMaster University, University of Minho, The University of Texas Health Science Center at Houston, National Institute of Mental Health and Neurosciences, University of California, Irvine, University Children's Hospital Zurich, Wake Forest University Health Sciences, Wake Forest University, Emma Kinderziekenhuis, Amsterdam Reproduction Development, University of Amsterdam, University of California, Los Angeles, Utrecht University, Mental Health Services, Centre Hospitalier Universitaire Vaudois, Capital Region of Denmark, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, University of Newcastle Australia, University Hospital Frankfurt, Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, National Center of Neurology and Psychiatry, National Institute of Mental Health, Universidad Autónoma de Madrid, National Human Genome Research Institute, National Institute of Mental Health, Deakin University, Institute of Mental Health, Columbia University Irving Medical Center, Norwegian University of Science and Technology, St. Joseph’s Healthcare Hamilton, New York University, University of Toyama, Leiden University Medical Center, Erasmus MC, Royal Children's Hospital, Universitat Politècnica de València, University of Bath, German Center for Neurodegenerative Diseases, NYU Langone Health, Seoul National University Hospital, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognitive Neuroimaging, Amsterdam UMC Location Vrije Universiteit Amsterdam, South African Medical Research Council
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Veterans Affairs, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Yale University, Biogen, University of Southern California, McLean Hospital, Georgia Institute of Technology, University of Pennsylvania, Emory University, Syracuse University, University of Minnesota, State University of New York, Aix-Marseille Université, University of East London, Brandeis University, Johns Hopkins University, University of Pittsburgh, Fundación Alicia Koplowitz, Universität Basel, Georgia State University, McGill University, Fundació la Marató de TV3, Philipps-Universität Marburg, Universidad de Sevilla, Norges Teknisk-Naturvitenskapelige Universitet, Sunovion, National University of Ireland, McMaster University, Health Research Board, Children’s Hospital of Wisconsin Research Institute, Pratt Foundation, University of Texas Health Science Center at Houston, Neuroscience Research Australia, Vanderbilt University Medical Center, Centre for Addiction and Mental Health Foundation, Murdoch Children's Research Institute, National Institute of Mental Health and Neurosciences, Amsterdam University Medical Centers, York University, National Institute for Health and Care Research, University of Cambridge, Imperial College London, King's College London, University of Oxford, European Commission, University of Bath, University of Sussex, University of Reading, South African Medical Research Council, University of Galway, Trinity College Dublin, Deutsche Forschungsgemeinschaft, Universiteit Leiden, Rijksuniversiteit Groningen, Stiftelsen för Strategisk Forskning, University of New South Wales, Deakin University, Monash University, University of Melbourne, ZonMw, Universiteit van Amsterdam, Universiteit Utrecht, Radboud Universiteit, Vrije Universiteit Amsterdam, Universiteit Maastricht, Russian Foundation for Basic Research, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Bundesministerium für Bildung und Forschung, Seoul National University, Technische Universität Dresden, Dalhousie University, Ministero della Salute, Lundbeckfonden, University of Toronto, Kunming Medical University, Karolinska Institutet, Seoul National University Hospital, Universiteit Stellenbosch, Universidad Autónoma de Madrid, Centre National de la Recherche Scientifique, Westfälische Wilhelms-Universität Münster, Universidade Federal do Rio Grande do Sul, Astellas Pharma, Fundação Bial, Universitetet i Bergen, Leids Universitair Medisch Centrum, Universitair Medisch Centrum Groningen, Deutsches Zentrum für Neurodegenerative Erkrankungen, Region Hovedstaden, Universitetet i Oslo, Universidade de São Paulo, Technische Universität München, Universitat de Barcelona, Radboud Universitair Medisch Centrum, Universidad de Cantabria, Centre Hospitalier Universitaire Vaudois, Universität Zürich, Centro de Investigación Biomédica en Red de Salud Mental, University of Cape Town, RWTH Aachen University, Università di Pisa, Rheinische Friedrich-Wilhelms-Universität Bonn, Chiba University, Julius-Maximilians-Universität Würzburg, Universidade do Minho, National Center of Neurology and Psychiatry, Innovative Medicines Initiative, Universitat Autònoma de Barcelona, Servier, Ministry of Science and Higher Education of the Russian Federation, H. Lundbeck A/S, Instituto de Investigación Marqués de Valdecilla, Universitätsklinikum Heidelberg, Amsterdam Neuroscience, National Institutes of Health, Directorate for Biological Sciences, Genentech, School of Medicine, New York University, University of California, Los Angeles, City, University of London, Allergan, Perelman School of Medicine, University of Pennsylvania, University of California, San Francisco, Medical School, University of Michigan, University of California, Irvine, Wake Forest School of Medicine, Campbell Family Mental Health Research Institute, State University of New York Upstate Medical University, Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Irving Medical Center, Columbia University, College of Medicine, Seoul National University, Greenwich Biosciences, NIHR Maudsley Biomedical Research Centre, Canadian Institutes of Health Research, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Medical Research Council, Menzies Centre for Australian Studies, King's College London, University of London, National Health and Medical Research Council, Japan Society for the Promotion of Science, Russian Academy of Sciences, Universitat Politècnica de València, Instituto de Salud Carlos III, European Regional Development Fund, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences, Nuclear Physics, Cilag
Awards: G1743590445, G2597303567, G274581676, Neurodevelopmental variation of intrinsic functional connectivity and its relationship to psychosis risk and gene expression, Brain trajectories in ADHD, G3326568298, G3693695666, G3726310188, Development of biomarkers for predicting disease progression and treatment response for schizophrenia using large-scale patient resources and iPS technology., G3800573915, Prediction of therapeutic effect of cognitive behavioral therapy for anxiety and obsessive-compulsive disorder, Development of a new diagnostic system based on brain pathophysiology of psychiatric disorders using multidimensional neuroimaging and genomics, G450822820, Evolution of Psychosis in Youth: Multimodal Risk and Resilience Markers, G4724859719, New avenues for the development of personalized medical interventions for neurological, oncologic and surgical disorders – “PersonalizedNOS”, Dissecting Causal Reasoning Abnormalities in Obsessive-Compulsive Disorder (OCD), G5530709631, G5541849108, G5677667711, The new treatment method of obsessive-compulsive disorder: Glutamatergic agents, UID/Multi/50026 .: ICVS/3B?s - Laboratório Associado, Instituto de Ciências da Vida e da Saúde / Grupo de Investigação em Biomateriais, Bio, Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders, Solar-Eclipse Computational Tools for Imaging Genetics, Hybrid GPU/CPU Computing Resource to Support Connectomic and Genomics, G757453727, G7965899483, Gene-Environment Interactions for Cortical Development and Schizophrenia, G8803761297, G893812777, Training in the Multiscale and Multimodal Analysis of Biomarkers in Alzheimer’s Disease, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, Yale Clinical and Translational Science Award, G903142205, G96847669
OpenAlex ID: W3080158422