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Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Authors
Yash Patel,Nadine Parker
Jean Shin,Derek Howard,Leon French,Sophia Thomopoulos,Elena Pozzi,Yoshinari Abe,Christoph Abé,Alan Anticevic,Martin Alda,André Alemán,Clara Alloza,Silvia Alonso‐Lana,Stephanie Ameis,Evdokia Anagnostou,Andrew McIntosh,Celso Arango,Paul Arnold,Philip Asherson,Francesca Assogna,Guillaume Auzias,Rosa Ayesa‐Arriola,Geor Bakker,Nerisa Banaj,Tobias Banaschewski,Cibele Bandeira,Baranov Aa,Núria Bargalló,Claiton Bau,Sarah Baumeister,Bernhard Baune,Mark Bellgrove,Francesco Benedetti,Alessandro Bertolino,Premika Boedhoe,Marco Boks,Irene Bollettini,Caterina Bonnín,Tiana Borgers,Stefan Borgwardt,Daniel Brandeis,Brian Brennan,Jason Bruggemann,Robin Bülow,Geraldo Busatto,Sara Calderoni,Vince Calhoun,Rosa Calvo,Erick Canales‐Rodríguez,Dara Cannon,Vaughan Carr,Nicola Cascella,Mara Cercignani,Tiffany Chaim‐Avancini,Anastasia Christakou,David Coghill,Annette Conzelmann,Benedicto Crespo‐Facorro,Ana Cubillo,Kathryn Cullen,Renata Cupertino,Eileen Daly,Udo Dannlowski,Christopher Davey,Damiaan Denys,Christine Deruelle,Annabella Giorgio,Erin Dickie,Danai Dima,Katharina Dohm,Stefan Ehrlich,Benjamin Ely,Tracy Erwin-Grabner,Thomas Ethofer,Damien Fair,Andreas Fallgatter,Stephen Faraone,Mar Fatjó‐Vilas,Jennifer Fedor,Kate Fitzgerald,Judith Ford,Thomas Frodl,Cynthia Fu,Janice Fullerton,Matt Gabel,David Glahn,Gloria Roberts,Tinatin Gogberashvili,José Goikolea,Ian Gotlib,Roberto Goya‐Maldonado,Hans Grabe,Melissa Green,Eugênio Grevet,Nynke Groenewold,Dominik Grotegerd,Oliver Gruber,Patricia Gruner,Amalia Guerrero‐Pedraza,Raquel Gur,Ruben Gur,Shlomi Haar,Bartholomeus Haarman,Jan Haavik,Tim Hahn,Tomáš Hájek,Ben Harrison,Neil Harrison,Catharina Hartman,Heather Whalley,Dirk Heslenfeld,Derrek Hibar,Eva Hilland,Yoshiyuki Hirano,Tiffany Ho,Pieter Hoekstra,Liesbeth Hoekstra,Sarah Hohmann,Hong Liu,Cyril Höschl,Marie Høvik,Fleur Howells,Igor Nenadić,Maria Jalbrzikowski,Anthony James,Joost Janssen,Fern Jaspers‐Fayer,Jian Xu,Rune Jonassen,Georgii Karkashadze,Joseph King,Tilo Kircher,Matthias Kirschner,Kathrin Koch,Peter Kochunov,Gregor Kohls,Kerstin Konrad,Bernd Krämer,Axel Krug,Jonna Kuntsi,Jun Kwon,Mikael Landén,Nils Landrø,Luisa Lázaro,Irina Lebedeva,Elisabeth Leehr,Sara Lera‐Miguel,Klaus‐Peter Lesch,Christine Löchner,Mário Louzã,Beatríz Luna,Astri Lundervold,Frank MacMaster,Luigi Maglanoc,Charles Malpas,Marı́a Portella,Rachel Marsh,Fiona Martyn,David Mataix‐Cols,Daniel Mathalon,Hazel McCarthy,Colm McDonald,Genevieve McPhilemy,Susanne Meinert,José Menchón,Luciano Minuzzi,Philip Mitchell,Carmen Moreno,Pedro Morgado,Filippo Muratori,Clodagh Murphy,Declan Murphy,Benson Mwangi,Leila Nabulsi,Akiko Nakagawa,Takashi Nakamae,Л. Намазова‐Баранова,Janardhanan Narayanaswamy,Neda Jahanshad,Danai Nguyen,Rosa Nicolau,Ruth Tuura,Kirsten O’Hearn,Jaap Oosterlaan,Nils Opel,Roel Ophoff,Bob Oranje,Víctor Foz,Bronwyn Overs,Yannis Paloyelis,Christos Pantelis,Mara Parellada,Paul Pauli,Maria Picó‐Pérez,Felipe Picon,Fabrizio Piras,Federica Piras,Kerstin Plessen,Edith Pomarol‐Clotet,Adrian Preda,Olga Puig,Yann Quidé,Joaquim Raduà,Josep Ramos‐Quiroga,Paul Rasser,Lisa Rauer,Janardhan Reddy,Ronny Redlich,Andreas Reif,Liesbeth Reneman,Jonathan Repple,Alessandra Retico,Vanesa Richarte,Anja Richter,Pedro Rosa,Katya Rubia,Ryota Hashimoto,Matthew Sacchet,Raymond Salvador,Javier Santonja,Kelvin Sarink,Salvador Sarró,Theodore Satterthwaite,Akira Sawa,Ulrich Schall,Peter Schofield,Anouk Schrantee,Jochen Seitz,Maurício Serpa,Esther Setién‐Suero,Philip Shaw,Devon Shook,Timothy Silk,Kang Sim,Schmitt Simon,Blair Simpson,Aditya Singh,Antonín Škoch,Norbert Skokauskas,Jair Soares,Noam Soreni,Carles Soriano‐Mas,Gianfranco Spalletta,Filip Španiel,Stephen Lawrie,Emily Stern,S. Stewart,Yoichiro Takayanagi,Henk Temmingh,David Tolin,David Tomeček,Diana Tordesillas‐Gutiérrez,Michela Tosetti,Anne Uhlmann,Thérèse Amelsvoort,Nic Wee,Steven Werff,Neeltje Haren,Guido Wingen,Alasdair Vance,Javier Vázquez-Bourgón,Daniela Vecchio,Ganesan Venkatasubramanian,Eduard Vieta,Óscar Vilarroya,Yolanda Vives‐Gilabert,Aristotle Voineskos,Henry Völzke,Georg Polier,Esther Walton,Thomas Weickert,Cynthia Weickert,Andrea Weideman,Katharina Wittfeld,Daniel Wolf,Mon-Ju Wu,Tony Yang,Kun Yang,Yuliya Yoncheva,Je‐Yeon Yun,Yuqi Cheng,Marcus Zanetti,Georg Ziegler,Barbara Franke,Martine Hoogman,Jan Buitelaar,Daan Rooij,Ole Andreassen,Christopher Ching,Dick Veltman,Lianne Schmaal,Dan Stein,Odile Heuvel,Jessica Turner,Theo Erp,Zdenka Pausová,Paul Thompson,Tomás Pauš,А. Баранов
+298 authors
,Martine RousselJournal
Published
Aug 26, 2020
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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.Paper PDF
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