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.
| Original language | English (US) |
|---|---|
| Journal | JAMA psychiatry |
| DOIs | |
| State | Accepted/In press - 2020 |
ASJC Scopus subject areas
- Psychiatry and Mental health
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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.; Bülow, Robin; Busatto, Geraldo F.; Calderoni, Sara; Calhoun, Vince D.; Calvo, Rosa; Canales-Rodríguez, Erick J.; Cannon, Dara M.; Carr, Vaughan J.; Cascella, Nicola; Cercignani, Mara; Chaim-Avancini, Tiffany M.; Christakou, Anastasia; Coghill, David; Conzelmann, Annette; Crespo-Facorro, Benedicto; Cubillo, Ana I.; Cullen, Kathryn R.; Cupertino, Renata B.; Daly, Eileen; Dannlowski, Udo; Davey, Christopher G.; Denys, Damiaan; Deruelle, Christine; Di Giorgio, Annabella; Dickie, Erin W.; Dima, Danai; Dohm, Katharina; Ehrlich, Stefan; Ely, Benjamin A.; Erwin-Grabner, Tracy; Ethofer, Thomas; Fair, Damien A.; Fallgatter, Andreas J.; Faraone, Stephen V.; Fatjó-Vilas, Mar; Fedor, Jennifer M.; Fitzgerald, Kate D.; Ford, Judith M.; Frodl, Thomas; Fu, Cynthia H.Y.; Fullerton, Janice M.; Gabel, Matt C.; Glahn, David C.; Roberts, Gloria; Gogberashvili, Tinatin; Goikolea, Jose M.; Gotlib, Ian H.; Goya-Maldonado, Roberto; Grabe, Hans J.; Green, Melissa J.; Grevet, Eugenio H.; Groenewold, Nynke A.; Grotegerd, Dominik; Gruber, Oliver; Gruner, Patricia; Guerrero-Pedraza, Amalia; Gur, Raquel E.; Gur, Ruben C.; Haar, Shlomi; Haarman, Bartholomeus C.M.; Haavik, Jan; Hahn, Tim; Hajek, Tomas; Harrison, Benjamin J.; Harrison, Neil A.; Hartman, Catharina A.; Whalley, Heather C.; Heslenfeld, Dirk J.; Hibar, Derrek P.; Hilland, Eva; Hirano, Yoshiyuki; Ho, Tiffany C.; Hoekstra, Pieter J.; Hoekstra, Liesbeth; Hohmann, Sarah; Hong, L. E.; Höschl, Cyril; Høvik, Marie F.; Howells, Fleur M.; Nenadic, Igor; Jalbrzikowski, Maria; James, Anthony C.; Janssen, Joost; Jaspers-Fayer, Fern; Xu, Jian; Jonassen, Rune; Karkashadze, Georgii; King, Joseph A.; Kircher, Tilo; Kirschner, Matthias; Koch, Kathrin; Kochunov, Peter; Kohls, Gregor; Konrad, Kerstin; Krämer, Bernd; Krug, Axel; Kuntsi, Jonna; Kwon, Jun Soo; Landén, Mikael; Landrø, Nils I.; Lazaro, Luisa; Lebedeva, Irina S.; Leehr, Elisabeth J.; Lera-Miguel, Sara; Lesch, Klaus Peter; Lochner, Christine; Louza, Mario R.; Luna, Beatriz; Lundervold, Astri J.; Macmaster, Frank P.; Maglanoc, Luigi A.; Malpas, Charles B.; Portella, Maria J.; Marsh, Rachel; Martyn, Fiona M.; Mataix-Cols, David; Mathalon, Daniel H.; McCarthy, Hazel; McDonald, Colm; McPhilemey, Genevieve; Meinert, Susanne; Menchón, José M.; Minuzzi, Luciano; Mitchell, Philip B.; Moreno, Carmen; Morgado, Pedro; Muratori, Filippo; Murphy, Clodagh M.; Murphy, Declan; Mwangi, Benson; Nabulsi, Leila; Nakagawa, Akiko; Nakamae, Takashi; Namazova, Leyla; Narayanaswamy, Janardhanan; Jahanshad, Neda; Nguyen, Danai D.; Nicolau, Rosa; O'Gorman Tuura, Ruth L.; O'Hearn, Kirsten; Oosterlaan, Jaap; Opel, Nils; Ophoff, Roel A.; Oranje, Bob; García De La Foz, Victor Ortiz; Overs, Bronwyn J.; Paloyelis, Yannis; Pantelis, Christos; Parellada, Mara; Pauli, Paul; Picó-Pérez, Maria; Picon, Felipe A.; Piras, Fabrizio; Piras, Federica; Plessen, Kerstin J.; Pomarol-Clotet, Edith; Preda, Adrian; Puig, Olga; Quidé, Yann; Radua, Joaquim; Ramos-Quiroga, J. Antoni; Rasser, Paul E.; Rauer, Lisa; Reddy, Janardhan; Redlich, Ronny; Reif, Andreas; Reneman, Liesbeth; Repple, Jonathan; Retico, Alessandra; Richarte, Vanesa; Richter, Anja; Rosa, Pedro G.P.; Rubia, Katya K.; Hashimoto, Ryota; Sacchet, Matthew D.; Salvador, Raymond; Santonja, Javier; Sarink, Kelvin; Sarró, Salvador; Satterthwaite, Theodore D.; Sawa, Akira; Schall, Ulrich; Schofield, Peter R.; Schrantee, Anouk; Seitz, Jochen; Serpa, Mauricio H.; Setién-Suero, Esther; Shaw, Philip; Shook, Devon; Silk, Tim J.; Sim, Kang; Simon, Schmitt; Simpson, Helen Blair; Singh, Aditya; Skoch, Antonin; Skokauskas, Norbert; Soares, Jair C.; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Spaniel, Filip; Lawrie, Stephen M.; Stern, Emily R.; Stewart, S. Evelyn; Takayanagi, Yoichiro; Temmingh, Henk S.; Tolin, David F.; Tomecek, David; Tordesillas-Gutiérrez, Diana; Tosetti, Michela; Uhlmann, Anne; Van Amelsvoort, Therese; Van Der Wee, Nic J.A.; Van Der Werff, Steven J.A.; Van Haren, Neeltje E.M.; Van Wingen, Guido A.; Vance, Alasdair; Vázquez-Bourgon, Javier; Vecchio, Daniela; Venkatasubramanian, Ganesan; Vieta, Eduard; Vilarroya, Oscar; Vives-Gilabert, Yolanda; Voineskos, Aristotle N.; Völzke, Henry; Von Polier, Georg G.; Walton, Esther; Weickert, Thomas W.; Weickert, Cynthia Shannon; Weideman, Andrea S.; Wittfeld, Katharina; Wolf, Daniel H.; Wu, Mon Ju; Yang, T. T.; Yang, Kun; Yoncheva, Yuliya; Yun, Je Yeon; Cheng, Yuqi; Zanetti, Marcus V.; Ziegler, Georg C.; Franke, Barbara; Hoogman, Martine; Buitelaar, Jan K.; Van Rooij, Daan; Andreassen, Ole A.; Ching, Christopher R.K.; Veltman, Dick J.; Schmaal, Lianne; Stein, Dan J.; Van Den Heuvel, Odile A.; Turner, Jessica A.; Van Erp, Theo G.M.; Pausova, Zdenka; Thompson, Paul M.; Paus, Tomáš.
In: JAMA psychiatry, 2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
AU - Patel, Yash
AU - Parker, Nadine
AU - Shin, Jean
AU - Howard, Derek
AU - French, Leon
AU - Thomopoulos, Sophia I.
AU - Pozzi, Elena
AU - Abe, Yoshinari
AU - Abé, Christoph
AU - Anticevic, Alan
AU - Alda, Martin
AU - Aleman, Andre
AU - Alloza, Clara
AU - Alonso-Lana, Silvia
AU - Ameis, Stephanie H.
AU - Anagnostou, Evdokia
AU - McIntosh, Andrew A.
AU - Arango, Celso
AU - Arnold, Paul D.
AU - Asherson, Philip
AU - Assogna, Francesca
AU - Auzias, Guillaume
AU - Ayesa-Arriola, Rosa
AU - Bakker, Geor
AU - Banaj, Nerisa
AU - Banaschewski, Tobias
AU - Bandeira, Cibele E.
AU - Baranov, Alexandr
AU - Bargalló, Núria
AU - Bau, Claiton H.D.
AU - Baumeister, Sarah
AU - Baune, Bernhard T.
AU - Bellgrove, Mark A.
AU - Benedetti, Francesco
AU - Bertolino, Alessandro
AU - Boedhoe, Premika S.W.
AU - Boks, Marco
AU - Bollettini, Irene
AU - Del Mar Bonnin, Caterina
AU - Borgers, Tiana
AU - Borgwardt, Stefan
AU - Brandeis, Daniel
AU - Brennan, Brian P.
AU - Bruggemann, Jason M.
AU - Bülow, Robin
AU - Busatto, Geraldo F.
AU - Calderoni, Sara
AU - Calhoun, Vince D.
AU - Calvo, Rosa
AU - Canales-Rodríguez, Erick J.
AU - Cannon, Dara M.
AU - Carr, Vaughan J.
AU - Cascella, Nicola
AU - Cercignani, Mara
AU - Chaim-Avancini, Tiffany M.
AU - Christakou, Anastasia
AU - Coghill, David
AU - Conzelmann, Annette
AU - Crespo-Facorro, Benedicto
AU - Cubillo, Ana I.
AU - Cullen, Kathryn R.
AU - Cupertino, Renata B.
AU - Daly, Eileen
AU - Dannlowski, Udo
AU - Davey, Christopher G.
AU - Denys, Damiaan
AU - Deruelle, Christine
AU - Di Giorgio, Annabella
AU - Dickie, Erin W.
AU - Dima, Danai
AU - Dohm, Katharina
AU - Ehrlich, Stefan
AU - Ely, Benjamin A.
AU - Erwin-Grabner, Tracy
AU - Ethofer, Thomas
AU - Fair, Damien A.
AU - Fallgatter, Andreas J.
AU - Faraone, Stephen V.
AU - Fatjó-Vilas, Mar
AU - Fedor, Jennifer M.
AU - Fitzgerald, Kate D.
AU - Ford, Judith M.
AU - Frodl, Thomas
AU - Fu, Cynthia H.Y.
AU - Fullerton, Janice M.
AU - Gabel, Matt C.
AU - Glahn, David C.
AU - Roberts, Gloria
AU - Gogberashvili, Tinatin
AU - Goikolea, Jose M.
AU - Gotlib, Ian H.
AU - Goya-Maldonado, Roberto
AU - Grabe, Hans J.
AU - Green, Melissa J.
AU - Grevet, Eugenio H.
AU - Groenewold, Nynke A.
AU - Grotegerd, Dominik
AU - Gruber, Oliver
AU - Gruner, Patricia
AU - Guerrero-Pedraza, Amalia
AU - Gur, Raquel E.
AU - Gur, Ruben C.
AU - Haar, Shlomi
AU - Haarman, Bartholomeus C.M.
AU - Haavik, Jan
AU - Hahn, Tim
AU - Hajek, Tomas
AU - Harrison, Benjamin J.
AU - Harrison, Neil A.
AU - Hartman, Catharina A.
AU - Whalley, Heather C.
AU - Heslenfeld, Dirk J.
AU - Hibar, Derrek P.
AU - Hilland, Eva
AU - Hirano, Yoshiyuki
AU - Ho, Tiffany C.
AU - Hoekstra, Pieter J.
AU - Hoekstra, Liesbeth
AU - Hohmann, Sarah
AU - Hong, L. E.
AU - Höschl, Cyril
AU - Høvik, Marie F.
AU - Howells, Fleur M.
AU - Nenadic, Igor
AU - Jalbrzikowski, Maria
AU - James, Anthony C.
AU - Janssen, Joost
AU - Jaspers-Fayer, Fern
AU - Xu, Jian
AU - Jonassen, Rune
AU - Karkashadze, Georgii
AU - King, Joseph A.
AU - Kircher, Tilo
AU - Kirschner, Matthias
AU - Koch, Kathrin
AU - Kochunov, Peter
AU - Kohls, Gregor
AU - Konrad, Kerstin
AU - Krämer, Bernd
AU - Krug, Axel
AU - Kuntsi, Jonna
AU - Kwon, Jun Soo
AU - Landén, Mikael
AU - Landrø, Nils I.
AU - Lazaro, Luisa
AU - Lebedeva, Irina S.
AU - Leehr, Elisabeth J.
AU - Lera-Miguel, Sara
AU - Lesch, Klaus Peter
AU - Lochner, Christine
AU - Louza, Mario R.
AU - Luna, Beatriz
AU - Lundervold, Astri J.
AU - Macmaster, Frank P.
AU - Maglanoc, Luigi A.
AU - Malpas, Charles B.
AU - Portella, Maria J.
AU - Marsh, Rachel
AU - Martyn, Fiona M.
AU - Mataix-Cols, David
AU - Mathalon, Daniel H.
AU - McCarthy, Hazel
AU - McDonald, Colm
AU - McPhilemey, Genevieve
AU - Meinert, Susanne
AU - Menchón, José M.
AU - Minuzzi, Luciano
AU - Mitchell, Philip B.
AU - Moreno, Carmen
AU - Morgado, Pedro
AU - Muratori, Filippo
AU - Murphy, Clodagh M.
AU - Murphy, Declan
AU - Mwangi, Benson
AU - Nabulsi, Leila
AU - Nakagawa, Akiko
AU - Nakamae, Takashi
AU - Namazova, Leyla
AU - Narayanaswamy, Janardhanan
AU - Jahanshad, Neda
AU - Nguyen, Danai D.
AU - Nicolau, Rosa
AU - O'Gorman Tuura, Ruth L.
AU - O'Hearn, Kirsten
AU - Oosterlaan, Jaap
AU - Opel, Nils
AU - Ophoff, Roel A.
AU - Oranje, Bob
AU - García De La Foz, Victor Ortiz
AU - Overs, Bronwyn J.
AU - Paloyelis, Yannis
AU - Pantelis, Christos
AU - Parellada, Mara
AU - Pauli, Paul
AU - Picó-Pérez, Maria
AU - Picon, Felipe A.
AU - Piras, Fabrizio
AU - Piras, Federica
AU - Plessen, Kerstin J.
AU - Pomarol-Clotet, Edith
AU - Preda, Adrian
AU - Puig, Olga
AU - Quidé, Yann
AU - Radua, Joaquim
AU - Ramos-Quiroga, J. Antoni
AU - Rasser, Paul E.
AU - Rauer, Lisa
AU - Reddy, Janardhan
AU - Redlich, Ronny
AU - Reif, Andreas
AU - Reneman, Liesbeth
AU - Repple, Jonathan
AU - Retico, Alessandra
AU - Richarte, Vanesa
AU - Richter, Anja
AU - Rosa, Pedro G.P.
AU - Rubia, Katya K.
AU - Hashimoto, Ryota
AU - Sacchet, Matthew D.
AU - Salvador, Raymond
AU - Santonja, Javier
AU - Sarink, Kelvin
AU - Sarró, Salvador
AU - Satterthwaite, Theodore D.
AU - Sawa, Akira
AU - Schall, Ulrich
AU - Schofield, Peter R.
AU - Schrantee, Anouk
AU - Seitz, Jochen
AU - Serpa, Mauricio H.
AU - Setién-Suero, Esther
AU - Shaw, Philip
AU - Shook, Devon
AU - Silk, Tim J.
AU - Sim, Kang
AU - Simon, Schmitt
AU - Simpson, Helen Blair
AU - Singh, Aditya
AU - Skoch, Antonin
AU - Skokauskas, Norbert
AU - Soares, Jair C.
AU - Soreni, Noam
AU - Soriano-Mas, Carles
AU - Spalletta, Gianfranco
AU - Spaniel, Filip
AU - Lawrie, Stephen M.
AU - Stern, Emily R.
AU - Stewart, S. Evelyn
AU - Takayanagi, Yoichiro
AU - Temmingh, Henk S.
AU - Tolin, David F.
AU - Tomecek, David
AU - Tordesillas-Gutiérrez, Diana
AU - Tosetti, Michela
AU - Uhlmann, Anne
AU - Van Amelsvoort, Therese
AU - Van Der Wee, Nic J.A.
AU - Van Der Werff, Steven J.A.
AU - Van Haren, Neeltje E.M.
AU - Van Wingen, Guido A.
AU - Vance, Alasdair
AU - Vázquez-Bourgon, Javier
AU - Vecchio, Daniela
AU - Venkatasubramanian, Ganesan
AU - Vieta, Eduard
AU - Vilarroya, Oscar
AU - Vives-Gilabert, Yolanda
AU - Voineskos, Aristotle N.
AU - Völzke, Henry
AU - Von Polier, Georg G.
AU - Walton, Esther
AU - Weickert, Thomas W.
AU - Weickert, Cynthia Shannon
AU - Weideman, Andrea S.
AU - Wittfeld, Katharina
AU - Wolf, Daniel H.
AU - Wu, Mon Ju
AU - Yang, T. T.
AU - Yang, Kun
AU - Yoncheva, Yuliya
AU - Yun, Je Yeon
AU - Cheng, Yuqi
AU - Zanetti, Marcus V.
AU - Ziegler, Georg C.
AU - Franke, Barbara
AU - Hoogman, Martine
AU - Buitelaar, Jan K.
AU - Van Rooij, Daan
AU - Andreassen, Ole A.
AU - Ching, Christopher R.K.
AU - Veltman, Dick J.
AU - Schmaal, Lianne
AU - Stein, Dan J.
AU - Van Den Heuvel, Odile A.
AU - Turner, Jessica A.
AU - Van Erp, Theo G.M.
AU - Pausova, Zdenka
AU - Thompson, Paul M.
AU - Paus, Tomáš
N1 - Publisher Copyright: © 2020 Lippincott Williams and Wilkins. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85093073209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85093073209&partnerID=8YFLogxK
U2 - 10.1001/jamapsychiatry.2020.2694
DO - 10.1001/jamapsychiatry.2020.2694
M3 - Article
C2 - 32857118
AN - SCOPUS:85093073209
JO - JAMA Psychiatry
JF - JAMA Psychiatry
SN - 2168-622X
ER -