Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Patel, Yash; Parker, Nadine; Shin, Jean; Howard, Derek; French, Leon; Thomopoulos, Sophia I.; Pozzi, Elena; Abe, Yoshinari; Abé, Christoph; Anticevic, Alan; Alda, Martin; Aleman, Andre; Alloza, Clara; Alonso-Lana, Silvia; Ameis, Stephanie H.; Anagnostou, Evdokia; McIntosh, Andrew A.; Arango, Celso; Arnold, Paul D.; Asherson, Philip; Assogna, Francesca; Auzias, Guillaume; Ayesa-Arriola, Rosa; Bakker, Geor; Banaj, Nerisa; Banaschewski, Tobias; Bandeira, Cibele E.; Baranov, Alexandr; Bargalló, Núria; Bau, Claiton H.D.; Baumeister, Sarah; Baune, Bernhard T.; Bellgrove, Mark A.; Benedetti, Francesco; Bertolino, Alessandro; Boedhoe, Premika S.W.; Boks, Marco; Bollettini, Irene; Del Mar Bonnin, Caterina; Borgers, Tiana; Borgwardt, Stefan; Brandeis, Daniel; Brennan, Brian P.; Bruggemann, Jason M.; Janssen, Joost; Murphy, Declan; Ophoff, Roel A.; Oranje, Bob; Shook, Devon; Van Haren, Neeltje E.M.
(2021) JAMA Psychiatry, volume 78, issue 1, pp. 47 - 63
(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),
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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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Keywords: Psychiatry and Mental health, Journal Article
ISSN: 2168-622X
Publisher: American Medical Association
Note: Funding Information: Dr Paloyelis reported grants from UK Medical Research Council G03001896 during the conduct of the study. Dr Pantelis reported grants from NHMRC and grants from Pratt Foundation during the conduct of the study; personal fees from Lundbeck, Australia Pty Ltd, grants from Lundbeck Foundation, and grants from NHMRC outside the submitted work. Dr Parellada reported other support from CIBERSAM during the conduct of the study; grants from ISCIII, Ministry of Health, Horizon2020, and the Alicia Koplowitz Foundation; and personal fees from Exeltis and Servier outside the submitted work. Dr Pauli reported grants from German Research Foundation during the conduct of the study. Dr Preda reported grants from University of California Irvine during the conduct of the study. Dr Puig reported grants from ISCIII, FEDER, and Fundació La Marató-TV3 during the conduct of the study. Dr Ramos-Quiroga reported grants and personal fees from Takeda, Janssen, Roche, Lilly, Novartis, Bial, Shionogui, Lundbeck, Almirall, Braingaze, Sincrolab, Medice, and Rubio and grants from Psious outside the submitted work. Dr Rauer reported personal fees from Federal Ministry of Education and Research (BMBF) Germany and the European Commission during the conduct of the study. Dr Reddy reported grants from Department of Science and Technology Government of India and grants from Department of Biotechnology Government of India during the conduct of the study. Dr Rubia reported grants from Takeda Pharmaceuticals outside the submitted work. Dr Schofield reported grants from NHMRC during the conduct of the study. Dr Serpa reported other support from Centro de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil) during the conduct of the study and Lundbeck Brasil outside the submitted work. Dr Shaw reported grants from Intramural Program of the National Institutes of Health during the conduct of the study. Dr Silk reported grants from National Health and Medical Research Council of Australia during the conduct of the study. Dr Simpson reported grants from National Institute of Mental Health and Biohaven Pharmaceuticals during the conduct of the study; other support from JAMA Psychiatry, UpToDate Inc, and Cambridge University Press outside the submitted work. Dr Soares reported grants from National Institutes of Health during the conduct of the study; personal fees from J&J, Alkermes, Sanofi, Sunovion, Pfizer, Sage, and Astellas; and grants from Compass Pathways, Merck, and Allergan outside the submitted work. Dr Spalletta reported grants from Italian Ministry of Health during the conduct of the study. Dr Lawrie reported grants and personal fees from Janssen and personal fees from Sunovion outside the submitted work. Dr Tolin reported personal fees from Mindyra LLC outside the submitted work. Dr Tomecek reported grants from Ministry of Education, Youth, and Sports during the conduct of the study. Dr van der Wee reported grants from Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw) during the conduct of the study. Dr Vieta reported grants and personal fees from Abbott, Janssen, Lundbeck, Sage, Sanofi-Aventis and personal fees from Allergan, Angelini, Sumitomo Pharma, Novartis, Otsuka, Richter, and Takeda outside the submitted work. Dr Voineskos reported grants from National Institute of Mental Health, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and University of Toronto outside the submitted work. Dr von Polier reported grants from Interdisciplinary Centre for Clinical Research (IZKF), Medical Faculty, RWTH Aachen University, during the conduct of the study. Dr T. Yang reported grants from the National Institute of Mental Health during the conduct of the study and from the National Institutes of Health outside the submitted work. Dr K. Yang reported grants from the National Institutes of Health during the conduct of the study. Dr Franke reported grants from NWO and European Commission H2020 during the conduct of the study and personal fees from Medice outside the submitted work. Dr Hoogman reported grants from Netherlands Scientific Organisation, Netherlands Scientific Organisation, the National Institutes of Health, and College of Neuropsychopharmacology during the conduct of the study. Dr Buitelaar reported personal fees from Janssen, Servier, Roche, Takeda/ Shire, Medice, and Angelini outside the submitted work. Dr Andreassen reported personal fees from Lundbeck and grants from KG Jebsen Stiftelsen, Norges forskningsråd, and South East Norway Health Authority during the conduct of the study and personal fees from HealthLytix outside the submitted work. Dr Ching reported grants from Biogen Inc outside the submitted work. Dr Stein reported personal fees from Lundbeck and Sun outside the submitted work. Dr van den Heuvel reported other support from Benecke outside the submitted work. Dr van Erp reported grants from the National Institutes of Health/National Institute of Mental Health during the conduct of the study. Dr Thompson reported grants from Biogen Inc outside the submitted work. Dr French owns shares in Cortexyme Inc unrelated to the topic of this manuscript. Dr Anagnostou has received consultation fees from Roche and Quadrant; research funding from Roche; in-kind supports from AMO pharma; royalties from APPI and Springer; and editorial honorarium from Wiley. Dr Brandeis serves as an unpaid scientiic consultant for an EU-funded neurofeedback trial. The present work is unrelated to the above grants and relationships. Dr Richarte was on the speakers’ bureau and/or acted as consultant for Takeda, Eli Lilly in the last 5 years. She also received travel awards (air tickets and hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Takeda, and Eli Lilly. Dr Preda reported grants and personal fees from NIH, NARSAD, Boehringer-Ingelheim, BMJ, EBSCO, Medscape, GLG, and Guidepoint. No other disclosures were reported. Funding Information: reported personal fees from Sanofi outside the submitted work. Dr Kircher reported grants from DFG during the conduct of the study. Dr Kuntsi reported grants from UK Medical Research Council during the conduct of the study and other support from Medice outside the submitted work. Dr Landén reports grants from Broad Institute, The Swedish Foundation for Strategic Research, and The Swedish Medical Research Council during the conduct of the study and personal fees from Lundbeck pharmaceuticals outside the submitted work. Dr Lazaro reported grants from Marato TV3 Foundation during the conduct of the study. Dr Lebedeva reported grants from Russian Foundation for basic research (RFBR), and grants from RFBR, personal fees from CoBrain project, and nonfinancial support from INPTS PEPTOGEN, AO outside the submitted work. Dr Lera-Miguel reported grants from Fundació Marató TV3-2009 during the conduct of the study. Dr Louza reported personal fees from Janssen, Lundbeck, Takeda, Hypera, and Cristalia outside the submitted work. Dr Portella reported grants from ISCIII, Spanish Government, personal fees from ISCIII, and other support from CIBERSAM during the conduct of the study. Dr Martyn reported grants from Health Research Board, Ireland, during the conduct of the study. Dr Mataix-Cols reported personal fees from UpToDate, Wolters Kluwer Health, and Elsevier outside the submitted work. Dr Mathalon reported personal fees from Aptinyx, Greenwich Biosciences, Cadent Therapeutics, and Boehringer-Ingelheim outside the submitted work. Dr McPhilemy reported grants from Health Research Board during the conduct of the study. Dr Menchón reports grants from Instituto de Salud Carlos III during the conduct of the study. Dr Minuzzi reported grants from Canadian Institutes of Health Research, Alternate Funding Plan (Department of Psychiatry, McMaster University), and Hamilton Academic Health Science Organization outside the submitted work. Dr Mitchell reported personal fees from Sanofi (Hangzhou) outside the submitted work. Dr Moreno reported personal fees from Janssen, Angelini, Servier, Nuvelution, Otsuka, and Lundbeck outside the submitted work. Dr Morgado reported grants from European Regional Development Fund (FEDER) funds through the Competitiveness Factors Operational Programme and by national funds, through the Foundation for Science and Technology, under the scope of the project POCI-01-0145-FEDER-007038 and grants from project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER during the conduct of the study; personal fees from Angelini, AstraZeneca, Bial, Biogen, Janssen-Cilag, Springer Healthcare; and grants from DGS-Portugal, Bial Foundation, 2CA-Braga outside the submitted work. Dr D. Murphy reported grants from EU Innovative Medicines Initiative (EU AIMS) and EU Innovative Medicines Initiative EU AIMS-2-TRIALS and other support from NIHR Maudsley Biomedical Research Centre during the conduct of the study and personal fees from Roche outside the submitted work. Dr Nakamae reported grants from JSPS KAKENHI during the conduct of the study. Dr Jahanshad reported grants from the National Institutes of Health during the conduct of the study and Biogen Inc outside the submitted work. Ms Overs reported grants from Australian NHMRC during the conduct of the study. Funding Information: reported grants, personal fees, and other support from Blackthorn Therapeutics outside the submitted work. Dr McIntosh reported grants from Wellcome Trust during the conduct of the study; grants from The Sackler Trust outside the submitted work. Dr Arango reported personal fees from Acadia, Angni, Gedeon Richter, Janssen-Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering-Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda outside the submitted work. Dr Arnold reported grants from Alberta Innovates Translational Health Chair in Child and Youth Mental Health and Ontario Brain Institute during the conduct of the study. Dr Asherson reported personal fees from Takeda, Medice, Novartis, and UKAAN and grants and personal fees from Janssen and Flynn Pharma outside the submitted work. Dr Assogna reported grants from Ministry of Health outside the submitted work. Dr Banaschewski reported personal fees from Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Lilly outside the submitted work and royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. Dr Baumeister reported grants from Deutsche Forschungsgesellschaft during the conduct of the study. Dr Bellgrove reported grants from Monash University during the conduct of the study. Dr Brennan reported grants from Eli Lilly; other support from Transcept Pharmaceuticals and Biohaven Pharmaceuticals; and personal fees from Rugen Therapeutics and Nobilis Therapeutics outside the submitted work. Dr Calvo reported grants from Marató TV3 Foundation during the conduct of the study. Dr Canales-Rodríguez reports grants from Instituto de Salud Carlos III during the conduct of the study. Dr Chaim-Avancini reported grants from Sao Paulo. The present investigation was supported by a 2010 NARSAD Independent Investigator Award (NARSAD: The Brain and Behavior Research Fund) awarded to Dr Busatto. Dr Busatto is also partially funded by CNPq-Brazil. Dr Zanetti was funded by FAPESP, Brazil (2013/ 03905-4), during the conduct of the study. Dr Coghill reported grants and personal fees from Shire/Takeda and personal fees from Medice, and Servier outside the submitted work. Dr Cullen reported grants from the National Institutes of Mental Health and grants from National Alliance for Research on Schizophrenia and Depression during the conduct of the study. Dr Dannlowski reported grants from Deutsche Forschungsgemeinschaft during the conduct of the study. Dr Davey reported grants from National Health and Medical Research Council during the conduct of the study. Dr Fair reported being a patent holder on the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software. He is also a co-founder of Nous Imaging Inc. Dr Faraone reported grants and other support from Shire/Takeda, Arbor, Sunovian, Otsuka, and Sunovion; personal fees from Akili, Alcobra, Enzymotec, Genomind, Ironshore, Rhodes, Tris, Vallon, Vaya, KemPharm, Lundbeck, NeuroLifeSciences, Neurovance, OnDosis, Supernus, Shire/Takeda, Elsevier, Guildford Press, Oxford University Press, and Arbor; and personal fees and other support from Akili and Ironshore; in addition, Dr Faraone had a patent to US Patent (US20130217707 A1) issued. Dr Frodl reported grants from Science Foundation Ireland during the conduct of the study and grants from Janssen-Cilag outside the submitted work. Dr Fullerton reported grants from Australian National Health and Medical Research Council (NHMRC), during the conduct of the study. Dr Gabel reported grants from Motor Neurone Disease Association outside the submitted work. Dr Goikolea reported personal fees from Lundbeck and Janssen-Cilag outside the submitted work. Dr Goya-Maldonado reported grants from German Federal Ministry of Education and Research (BMBF: 01 ZX 1507) during the conduct of the study and grants from German Federal Ministry of Education and Research (BMBF: 01 ZX 1507) outside the submitted work. Dr Grabe reported grants from German Ministry of Research and Education and German Research Foundation during the conduct of the study; grants and personal fees from Fresenius Medical Care; and personal fees from Neuraxpharm, Servier, and Janssen-Cilag outside the submitted work. Dr Grevet reported personal fees from Takeda outside the submitted work. Dr Groenewold reported grants from Gratama Foundation, the Netherlands, during the conduct of the study. Dr R. C. Gur reported grants from the National Institute of Mental Health during the conduct of the study. Dr Haarman reported grants from European Commission EU-FP7-HEALTH-222963 'MOODIN-FLAME' and European Commission EU-FP7-PEOPLE-286334 'PSYCHAID' during the conduct of the study and grants from ZonMW PostDoc Fellowship 636320010 and Stanley Medical Research Institute 18T-004 outside the submitted work. Dr Haavik reported personal fees from Shire, Medice, and Biocodex outside the submitted work. Dr Hajek reported grants from Canadian Institutes of Health Research during the conduct of the study. Dr B. Harrison reported grants from Australian NHMRC during the conduct of the study. Dr Hibar reported other support from Genentech Inc outside the submitted work. Dr Hirano reported grants from Japan Agency for Medical Research and Development and Japan Society for the Promotion of Science during the conduct of the study and outside the submitted work. Dr P. Hoekstra reported personal fees from Takeda outside the submitted work. Dr Hohmann reported grants from Deutsche Forschungsgemeinschaft (DFG) during the conduct of the study. Dr Hong reported receiving or is planning to receive research funding or consulting fees from Mitsubishi, Your Energy Systems LLC, Neuralstem, Taisho, Heptares, Pfizer, Luye Pharma, Sound Pharma, Takeda, and Regeneron. Dr Höschl reports grants from the government during the conduct of the study; other support from Lundbeck International Neuroscience Foundation; personal fees from Zentiva, Servier, Angelini, and Sanofi outside the submitted work. Dr Nenadic reported grants from DFG during the conduct of the study. Dr Jalbrzikowski reported grants from National Institute of Mental Health during the conduct of the study. Dr Karkashadze Publisher Copyright: © 2021 American Medical Association. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
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