Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Authors: 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
Journal: JAMA Psychiatry (2020)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Main Outcomes and Measures</h3> Interregional profiles of group difference in cortical thickness between cases and controls. <h3>Results</h3> 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. <h3>Conclusions and Relevance</h3> 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.