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. 2021 Jan 1;78(1):47-63.
doi: 10.1001/jamapsychiatry.2020.2694.

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Writing Committee for the Attention-Deficit/Hyperactivity Disorder; Autism Spectrum Disorder; Bipolar Disorder; Major Depressive Disorder; Obsessive-Compulsive Disorder; and Schizophrenia ENIGMA Working Groups; Yash Patel  1   2 , Nadine Parker  1   2 , Jean Shin  3 , Derek Howard  4 , Leon French  4 , Sophia I Thomopoulos  5 , Elena Pozzi  6 , Yoshinari Abe  7 , Christoph Abé  8 , Alan Anticevic  9 , Martin Alda  10 , Andre Aleman  11 , Clara Alloza  12 , Silvia Alonso-Lana  13 , Stephanie H Ameis  14 , Evdokia Anagnostou  15 , Andrew A McIntosh  16 , Celso Arango  17 , Paul D Arnold  18 , Philip Asherson  19 , Francesca Assogna  20 , Guillaume Auzias  21 , Rosa Ayesa-Arriola  22 , Geor Bakker  23 , Nerisa Banaj  20 , Tobias Banaschewski  24 , Cibele E Bandeira  25 , Alexandr Baranov  26 , Núria Bargalló  27 , Claiton H D Bau  25 , Sarah Baumeister  24 , Bernhard T Baune  28 , Mark A Bellgrove  29 , Francesco Benedetti  30 , Alessandro Bertolino  31 , Premika S W Boedhoe  32 , Marco Boks  33 , Irene Bollettini  30 , Caterina Del Mar Bonnin  34 , Tiana Borgers  28 , Stefan Borgwardt  35 , Daniel Brandeis  24 , Brian P Brennan  36 , Jason M Bruggemann  37 , Robin Bülow  38 , Geraldo F Busatto  39 , Sara Calderoni  40   41 , Vince D Calhoun  42 , Rosa Calvo  43   44 , Erick J Canales-Rodríguez  13 , Dara M Cannon  45 , Vaughan J Carr  46 , Nicola Cascella  47 , Mara Cercignani  48 , Tiffany M Chaim-Avancini  39 , Anastasia Christakou  49 , David Coghill  50 , Annette Conzelmann  51 , Benedicto Crespo-Facorro  52 , Ana I Cubillo  53 , Kathryn R Cullen  54 , Renata B Cupertino  25 , Eileen Daly  55 , Udo Dannlowski  28 , Christopher G Davey  56 , Damiaan Denys  57 , Christine Deruelle  21 , Annabella Di Giorgio  58 , Erin W Dickie  59 , Danai Dima  60 , Katharina Dohm  28 , Stefan Ehrlich  61 , Benjamin A Ely  62 , Tracy Erwin-Grabner  63 , Thomas Ethofer  64 , Damien A Fair  65 , Andreas J Fallgatter  64 , Stephen V Faraone  66 , Mar Fatjó-Vilas  13 , Jennifer M Fedor  67 , Kate D Fitzgerald  68 , Judith M Ford  69 , Thomas Frodl  70 , Cynthia H Y Fu  71 , Janice M Fullerton  72 , Matt C Gabel  73 , David C Glahn  74 , Gloria Roberts  46 , Tinatin Gogberashvili  75 , Jose M Goikolea  34 , Ian H Gotlib  76 , Roberto Goya-Maldonado  63 , Hans J Grabe  77 , Melissa J Green  46 , Eugenio H Grevet  78 , Nynke A Groenewold  79 , Dominik Grotegerd  28 , Oliver Gruber  80 , Patricia Gruner  9 , Amalia Guerrero-Pedraza  81 , Raquel E Gur  82 , Ruben C Gur  82 , Shlomi Haar  83 , Bartholomeus C M Haarman  84 , Jan Haavik  85 , Tim Hahn  28 , Tomas Hajek  10 , Benjamin J Harrison  86 , Neil A Harrison  48 , Catharina A Hartman  87 , Heather C Whalley  16 , Dirk J Heslenfeld  88 , Derrek P Hibar  89 , Eva Hilland  90 , Yoshiyuki Hirano  91 , Tiffany C Ho  92 , Pieter J Hoekstra  93 , Liesbeth Hoekstra  94 , Sarah Hohmann  24 , L E Hong  95 , Cyril Höschl  96 , Marie F Høvik  97 , Fleur M Howells  98 , Igor Nenadic  99 , Maria Jalbrzikowski  67 , Anthony C James  100 , Joost Janssen  12 , Fern Jaspers-Fayer  101 , Jian Xu  102 , Rune Jonassen  90 , Georgii Karkashadze  103 , Joseph A King  61 , Tilo Kircher  104 , Matthias Kirschner  105 , Kathrin Koch  106 , Peter Kochunov  95 , Gregor Kohls  107 , Kerstin Konrad  108 , Bernd Krämer  80 , Axel Krug  104   109 , Jonna Kuntsi  19 , Jun Soo Kwon  110 , Mikael Landén  111 , Nils I Landrø  90 , Luisa Lazaro  43   44 , Irina S Lebedeva  112 , Elisabeth J Leehr  28 , Sara Lera-Miguel  43 , Klaus-Peter Lesch  113 , Christine Lochner  114 , Mario R Louza  115 , Beatriz Luna  67 , Astri J Lundervold  116 , Frank P MacMaster  117 , Luigi A Maglanoc  118 , Charles B Malpas  119 , Maria J Portella  120 , Rachel Marsh  121 , Fiona M Martyn  45 , David Mataix-Cols  122 , Daniel H Mathalon  92 , Hazel McCarthy  70 , Colm McDonald  45 , Genevieve McPhilemy  45 , Susanne Meinert  28 , José M Menchón  123 , Luciano Minuzzi  124 , Philip B Mitchell  46 , Carmen Moreno  17 , Pedro Morgado  125 , Filippo Muratori  40   41 , Clodagh M Murphy  126 , Declan Murphy  127 , Benson Mwangi  128 , Leila Nabulsi  45 , Akiko Nakagawa  91 , Takashi Nakamae  7 , Leyla Namazova  26 , Janardhanan Narayanaswamy  129 , Neda Jahanshad  5 , Danai D Nguyen  130 , Rosa Nicolau  43 , Ruth L O'Gorman Tuura  131 , Kirsten O'Hearn  132 , Jaap Oosterlaan  133 , Nils Opel  28 , Roel A Ophoff  134 , Bob Oranje  135 , Victor Ortiz García de la Foz  136 , Bronwyn J Overs  137 , Yannis Paloyelis  138 , Christos Pantelis  139 , Mara Parellada  17 , Paul Pauli  140 , Maria Picó-Pérez  125 , Felipe A Picon  78 , Fabrizio Piras  20 , Federica Piras  20 , Kerstin J Plessen  141 , Edith Pomarol-Clotet  13 , Adrian Preda  142 , Olga Puig  43   44 , Yann Quidé  46   72 , Joaquim Radua  34 , J Antoni Ramos-Quiroga  143   144 , Paul E Rasser  145 , Lisa Rauer  80 , Janardhan Reddy  129 , Ronny Redlich  28 , Andreas Reif  146 , Liesbeth Reneman  147 , Jonathan Repple  28 , Alessandra Retico  148 , Vanesa Richarte  143   144 , Anja Richter  80 , Pedro G P Rosa  39 , Katya K Rubia  149 , Ryota Hashimoto  150 , Matthew D Sacchet  151 , Raymond Salvador  13 , Javier Santonja  152 , Kelvin Sarink  28 , Salvador Sarró  13 , Theodore D Satterthwaite  82 , Akira Sawa  47 , Ulrich Schall  145 , Peter R Schofield  153 , Anouk Schrantee  147 , Jochen Seitz  154 , Mauricio H Serpa  39 , Esther Setién-Suero  22 , Philip Shaw  155 , Devon Shook  135 , Tim J Silk  156 , Kang Sim  157 , Schmitt Simon  99 , Helen Blair Simpson  158 , Aditya Singh  63 , Antonin Skoch  96 , Norbert Skokauskas  159 , Jair C Soares  128 , Noam Soreni  160 , Carles Soriano-Mas  123 , Gianfranco Spalletta  20 , Filip Spaniel  96 , Stephen M Lawrie  16 , Emily R Stern  161 , S Evelyn Stewart  101 , Yoichiro Takayanagi  162 , Henk S Temmingh  79 , David F Tolin  163 , David Tomecek  96 , Diana Tordesillas-Gutiérrez  136 , Michela Tosetti  164 , Anne Uhlmann  79 , Therese van Amelsvoort  165 , Nic J A van der Wee  166 , Steven J A van der Werff  166 , Neeltje E M van Haren  167 , Guido A van Wingen  168 , Alasdair Vance  169 , Javier Vázquez-Bourgon  22 , Daniela Vecchio  20 , Ganesan Venkatasubramanian  129 , Eduard Vieta  34   170 , Oscar Vilarroya  171 , Yolanda Vives-Gilabert  172 , Aristotle N Voineskos  59 , Henry Völzke  173 , Georg G von Polier  174 , Esther Walton  175 , Thomas W Weickert  37 , Cynthia Shannon Weickert  37 , Andrea S Weideman  176 , Katharina Wittfeld  177 , Daniel H Wolf  82 , Mon-Ju Wu  128 , T T Yang  178 , Kun Yang  47 , Yuliya Yoncheva  179 , Je-Yeon Yun  180 , Yuqi Cheng  181 , Marcus V Zanetti  39 , Georg C Ziegler  113 , Barbara Franke  182 , Martine Hoogman  183 , Jan K Buitelaar  184 , Daan van Rooij  185 , Ole A Andreassen  186 , Christopher R K Ching  5 , Dick J Veltman  187 , Lianne Schmaal  6   188 , Dan J Stein  189 , Odile A van den Heuvel  32 , Jessica A Turner  190 , Theo G M van Erp  176 , Zdenka Pausova  3 , Paul M Thompson  5 , Tomáš Paus  1   2   191
Affiliations

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Writing Committee for the Attention-Deficit/Hyperactivity Disorder et al. JAMA Psychiatry. .

Erratum in

  • Error in Nonbyline Author Name.
    [No authors listed] [No authors listed] JAMA Psychiatry. 2021 Jan 1;78(1):112. doi: 10.1001/jamapsychiatry.2020.3094. JAMA Psychiatry. 2021. PMID: 32936223 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Anticevic 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 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. 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 scientific 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.

Figures

Figure 1.
Figure 1.. Profiles of Group Differences in Cortical Thickness (Left Hemisphere Only) Between Cases and Controls
Profiles of group differences in cortical thickness (left hemisphere only) between cases and controls across the 6 psychiatric disorders investigated. Group differences are adjusted for age, sex, and other site-specific variables. Error bars represent 95% confidence intervals. Estimates less than zero represent thinner cortex in cases as compared with controls.
Figure 2.
Figure 2.. Phenotypic and Genetic Similarity Between Psychiatric Disorders
A, Cross-disorder correlation of group differences in cortical thickness (profiles from Figure 1). B, Cross-disorder genetic correlation (linkage disequilibrium score regression) derived from Brainstorm et al. C, Plot of genetic correlation against phenotypic (magnetic resonance imaging [MRI]–derived difference in thickness) correlations between psychiatric disorders with a linear model fit (blue line, R2 = 0.27; Mantels P = .03, Pearson P <.05). ADHD indicates attention-deficit/hyperactivity disorder, ASD, autism spectrum disorder; BD, bipolar disorder; MDD, major depressive disorder, OCD, obsessive-compulsive disorder; SCZ, schizophrenia.
Figure 3.
Figure 3.. Virtual Histology of Group Differences in Cortical Thickness
Results from virtual histology. Distribution of correlation coefficients between cell-specific gene expression profiles and group differences in cortical thickness for the 6 psychiatric disorders. ADHD indicates attention-deficit/hyperactivity disorder, ASD, autism spectrum disorder; BD, bipolar disorder; bichor, biweight midcorrelation; MDD, major depressive disorder, OCD, obsessive-compulsive disorder; SCZ, schizophrenia. aFalse discovery rate P <.05.
Figure 4.
Figure 4.. Principal Component 1 From the 6 Group Difference Profiles
Principal component analysis of profiles of group differences across 6 psychiatric disorders. A. First principal component (PC1) plotted across the 34 regions of the left hemisphere. First principal component values are scaled down to have a maximum of zero to facilitate interpretation; negative values reflect greater differences in cortical thickness between cases and controls shared by the 6 disorders. Unscaled values are presented in eFigure 3 in the Supplement. B. Distribution of correlation coefficients between cell-specific gene expression and PC1 profile. bicor indicates biweight midcorrelation; Oligo, oligodendrocyte. aFalse discovery rate P <.05.
Figure 5.
Figure 5.. Trajectories of Expression for Genes Associated With the Shared Profile of Group Differences in Cortical Thickness
Life span trajectory in gene expression of first principal component (PC1)–CA1 coexpressed genes. Each line represents a fitted LOESS model for the expression of a given gene. Genes and their fitted models are colored based on clustering based on temporal trajectories. First principal component–CA1 coexpressed genes were generated using coexpression of seed genes, namely genes that associate with PC1 profile and the 103 CA1 pyramidal specific genes passing false discovery rate P <.05. Gene ontology (GO) enrichment analysis of the prenatal cluster (B) and postnatal cluster (C). Dot size (count) for enrichment analysis (B,C) represents the number of genes that are within the co-expression gene panels as well as a particular GO group (y-axis).
See this image and copyright information in PMC

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