Abstract
BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.
METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.
RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.
CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Originalsprache | Englisch |
---|---|
Seiten (von - bis) | 299-313 |
Seitenumfang | 15 |
Fachzeitschrift | Biological Psychiatry |
Jahrgang | 92 |
Ausgabenummer | 4 |
DOIs | |
Publikationsstatus | Veröffentlicht - 15 Aug. 2022 |
Extern publiziert | Ja |
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness. / Patel, Yash; Shin, Jean; Abé, Christoph et al.
in: Biological Psychiatry, Jahrgang 92, Nr. 4, 15.08.2022, S. 299-313.Publikation: Beitrag in Fachzeitschrift (peer-reviewed) › Artikel in Fachzeitschrift
TY - JOUR
T1 - Virtual Ontogeny of Cortical Growth Preceding Mental Illness
AU - Patel, Yash
AU - Shin, Jean
AU - Abé, Christoph
AU - Agartz, Ingrid
AU - Alloza, Clara
AU - Alnæs, Dag
AU - Ambrogi, Sonia
AU - Antonucci, Linda A
AU - Arango, Celso
AU - Arolt, Volker
AU - Auzias, Guillaume
AU - Ayesa-Arriola, Rosa
AU - Banaj, Nerisa
AU - Banaschewski, Tobias
AU - Bandeira, Cibele
AU - Başgöze, Zeynep
AU - Cupertino, Renata Basso
AU - Bau, Claiton H D
AU - Bauer, Jochen
AU - Baumeister, Sarah
AU - Bernardoni, Fabio
AU - Bertolino, Alessandro
AU - Bonnin, Caterina Del Mar
AU - Brandeis, Daniel
AU - Brem, Silvia
AU - Bruggemann, Jason
AU - Bülow, Robin
AU - Bustillo, Juan R
AU - Calderoni, Sara
AU - Calvo, Rosa
AU - Canales-Rodríguez, Erick J
AU - Cannon, Dara M
AU - Carmona, Susanna
AU - Carr, Vaughan J
AU - Catts, Stanley V
AU - Chenji, Sneha
AU - Chew, Qian Hui
AU - Coghill, David
AU - Connolly, Colm G
AU - Conzelmann, Annette
AU - Craven, Alexander R
AU - Crespo-Facorro, Benedicto
AU - Cullen, Kathryn
AU - Dahl, Andreas
AU - Dannlowski, Udo
AU - Davey, Christopher G
AU - Deruelle, Christine
AU - Díaz-Caneja, Covadonga M
AU - Dohm, Katharina
AU - Willinger, David
N1 - Funding Information: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study ( https://abcdstudy.org ), held in the National Institute of Mental Health (NIMH) Data Archive. This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9 to 10 and follow them over 10 years into early adulthood. The ABCD Study is supported by the National Institutes of Health (NIH) and additional federal partners under Grant Nos. U01DA041048 , U01DA050989 , U01DA051016 , U01DA041022 , U01DA051018 , U01DA051037 , U01DA050987 , U01DA041174 , U01DA041106 , U01DA041117 , U01DA041028 , U01DA041134 , U01DA050988 , U01DA051039 , U01DA041156 , U01DA041025 , U01DA041120 , U01DA051038 , U01DA041148 , U01DA041093 , U01DA041089 , U24DA041123 , and U24DA041147 . A full list of supporters is available at https://abcdstudy.org/federal-partners.html . A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/consortium_members/ . ABCD Consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. Funding Information: Other acknowledgments specific to individual authors are provided in parentheses. Natural Sciences and Engineering Research Council of Canada Graduate Scholarships – Doctoral program (YP); funding by the Research Council of Norway (Grant No. 223273) and KG Jebsen Stiftelsen (to IA, OAA) and by the South-Eastern Norway Regional Health Authority (Grant Nos. 2019107, 2020086 [to DA]). The Neurofeedback study was partly funded by the project D8 of the Deutsche Forschungsgesellschaft collaborative research center 636. We would like to acknowledge Isabella Wolf and Regina Boecker-Schlier. (TB, SBa, DB, SH, NH, AK). The study cohort was financed by Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant Nos. 476529/2012-3, 466722/2014-1, 424041/2016-2; 310619/2019-0), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and FIPE-HCPA 160600, and Fundo de Amparo à Pesquisa do Rio Grande do Sul (Grant No. 19/2551-0001731-6 [to CB, EHG, FPic, MTa]). The study was funded by the National Institute of Mental Health (Grant No. K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (Grant No. P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women’s Health Seed Grant, University of Minnesota (to ZB, KC). The study cohort was financed by Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant Nos. 476529/2012-3, 466722/2014-1, and 424041/2016-2), CAPES - Finance Code 001 and FIPE-HCPA 160600, and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant Nos. PqG-19/2551-0001731-6 and PqG-19/2551-0001668-9 [CHDB]). This study was supported by the Swiss National Science Foundation (Grant No. #320030_130237 [to SBr]) and the Hartmann Müller Foundation (Grant No. 1460 [to SBr]). This study was supported by the Italian Ministry of Health (Grant No. RC 2768566/2020-2021 [to SCal, FM]); the Spanish Ministry of Science and Innovation (Grant No. PI09/1588 [to RC]) ISCIII and the Fondo Europeo de Desarrollo Regional (FEDER) (Grant No. 091510 from La Marató-TV3 Foundation [to RC]); and Health Research Board (HRA-POR-324 [to DMC, LN]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, SIG /1103 [to KS]), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS, QHC]), TENOVUS Dundee (to DC), the German Research Foundation (Grant Nos. FOR2107 DA1151/5-1 and DA1151/5-2; SFB-TRR58; Projects C09 and Z02 [to UD]) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (Grant No. Dan3/012/17 [to UD]). Data collection and sharing for this project was partially funded by the Multimodal Treatment Study for ADHD (National Institutes of Drug Abuse Contract No. HHSN271200800009C [to JE, LT]). Support was provided by the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung Grant No. 01 ZX 1507, ‘‘PreNeSt - e:Med’’ [to TE-G]) and NIH MH083968 and Desert-Pacific Mental Illness Research, Education, and Clinical Center (to LTE). This work was supported by the Department of Veterans Affairs (Senior Research Career Scientist award and VA 1I01 CX0004971 [to JMF]). CIBERSAM, AGAUR (to PF-C, EP-C, SS). The “Kids and Sibs” Study was supported by the Australian National Medical and Health Research Council (Program Grant No. 1037196 and Investigator Grant No. 1177991 [to PBM], Project Grant No. 1066177 [to JMF]), the Lansdowne Foundation, Good Talk, and the Keith Pettigrew Family Bequest (to PM). JMF gratefully acknowledges the Janette Mary O’Neil Research Fellowship (to JFu, PM, BO, GR). LFu was supported by an Australian Rotary Health/Ian Parker Bipolar Research Fund postgraduate scholarship. Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation and the Society of Mental Health Research (to LFu). The Meath Foundation, Tallaght University Hospital, and The National Children's Hospital Foundation (to LG). This study was supported by Grant Nos. R01AA012207, RO1MH123163, RO1NS114628, R01 EB015611, and U01 MH108148 (to SG, PK); NIH (Grant No. R37MH101495 [to IG]), the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung: Grant No. 01 ZX 1507, ‘‘PreNeSt - e:Med’’ [to RG-M]). The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net (CMR) ( http://www.medizin.uni-greifswald.de/icm ) of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg- West Pomerania. MRI scans in SHIP and SHIP-TREND have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. This study was further supported by the EU-JPND Funding for BRIDGET (FKZ:01ED1615 [to HJG]), National Health and Medical Research Council of Australia (NHMRC) Project (Grant No. 630471 [to MG]), a Carnegie Developing Emerging Academic Leaders Fellowship (to NAG), and Stiftelsen KGJebsen (Grant No. SKGJ-MED02 [to JH]). Funding Information: This work was supported by the German Research Foundation (DFG Grant Nos. HA7070/2-2, HA7070/3, HA7070/4 [to TH]) and IZKF of the medical faculty of Münster (Grants No. Dan3/012/17 [to UD] and MzH 3/020/20 [to TH]), and NHMRC projects (Grant No. 1064643 [to BJH] and 1024570 [to CGD]). The CIAM study was supported by the University of Cape Town Research Committee, South African National Research Foundation, and the South African Medical Research Council (principal investigator [PI], Fleur M. Howells) and Grant No. R01MH117601 (to NJ). This work was funded by the German Research Foundation (Grant Nos. FOR2107 JA 1890/7-1 and FOR2107 JA 1890/7-2 [to AJ]) and Swinburne University scholarship/Australian Postgraduate Award (to JK). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to JK). This work was funded by the German Research Foundation (Grant Nos. FOR2107 KI588/14-1 and FOR2107 KI588/14-2 [to TK]). The St. Göran study was supported by grants from the Swedish Research Council (Grant No. 2018-02653 [to ML]), the Swedish foundation for Strategic Research (Grant No. KF10-0039 [to ML]), the Swedish Brain foundation (Grant No. FO2020-0261 [to ML]), and the Swedish Government under the LUA/ALF agreement (Grant Nos. ALF 20170019 and ALFGBG-716801 [to ML]). This work was supported by RFBR (Grant No. 20-013-00748 [to IL, AST]) and funded by the Health Research Board (Grant No. HRA_POR/2011/100 [to CM]). The Australian Schizophrenia Research Bank (ASRB) was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This work was supported by Deutsche Forschungsgemeinschaft (Grant Nos. DFG NE 2254/2-1, NE 2254/3-1, NE2254/4-1 [to IN]), the University Research Priority Program “Integrative Human Physiology” at the University of Zurich (to ROT), an NHMRC Senior Principal Research Fellowship (Grant No. 1105825 [to CPa]), an NHMRC L3 Investigator Grant (Grant No. 1196508 [to CP]), and NHMRC Program Grant (Grant No. 1150083 [to CPa]). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (Agreement No. 798181 [to GP]). ASRB was supported by the NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. The Imaging Genetics in Psychosis study was funded by Project Grants from the NHMRC (Grant Nos. APP630471 and APP1081603 [to YQ]) and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (Grant No. CE110001021 [to YQ]). This work was supported by the Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI11/01766 and CPII19/00009 [to JR]), co-financed by European Regional Development Fund funds from the European Commission (“A Way of Making Europe”). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. SR was supported by an NHMRC Senior Fellowship (Grant No. GNT1154651). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to SR). This work was supported by NIHR; MRC (to KR), NIH (Grant Nos. MH-094268, MH-105660, and MH-107730 [to ASS]). The Neuroimaging of the Children's Attention Project cohort was funded by NHMRC, Australia (Grant No. 1065895). Earlier funding for the cohort as also provided by NHMRC (Grant No. 1008522) and a grant from the Collier Foundation. The ACPU cohort was funded by NHMRC, Australia (Project Grant Nos. 384419 and 569533 [to TS]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, and SIG /1103), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS]), and the Ministry of Health, Czech Republic - conceptual development of research organization (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001” [to ASk]). This study was supported by the Italian Ministry of Health (Grant No. RC/17-18-19-20-21/A [to GS]) and Ministry of Health of the Czech Republic (Grant No. NU20-04-00393 [to FS]). The Drakenstein Child Health Study (DCHS) cohort is funded by the Bill and Melinda Gates Foundation (Grant No. OPP 1017641) and the South African Medical Research Council. This DCHS contribution was made possible in part by a grant from Carnegie Corporation of New York. The statements made and views expressed are solely the responsibility of the author (DJS). STRADL study was supported and funded by the Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (Grant No. 104036/Z/14/Z), and the Medical Research Council Mental Health Pathfinder Award “Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders” (MRC, Grant No. MC_PC_17209). Scottish Bipolar Family Study (SBFS) was supported by National Health Service Research Scotland, through the Scottish Mental Health Research Network ( www.smhrn.org.uk ), who provided assistance with subject recruitment and assessments. SBFS was conducted at the Brain Research Imaging Centre ( http://www.bric.ed.ac.uk ), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence, http://www.sinapse.ac.uk ). Processing of the datasets used the resources provided by the Edinburgh Compute and Data Facility ( http://www.ecdf.ed.ac.uk/ ) (ASt). TVR was supported by an NHMRC Early Career Fellowship (Grant No. GNT1088785). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to TVR). EV was supported by the Spanish Ministry of Science and Innovation (PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the FEDER; the Instituto de Salud Carlos III; the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental); by the CERCA Programme/Generalitat de Catalunya and the Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (Grant No. 2017SGR1355). This study was also supported by the Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Grant No. SLT006/17/00345) and the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant Nos. 754907 and EU.3.1.3 [to EB]; Treating and managing disease: Grant No. 945151 [to EV]). This study was supported by the National Center for Complementary and Integrative Health (Grant Nos. R21AT009173 and R61AT009864 [to TTY]); by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI (Grant No. UL1TR001872 [to TTY]); by the American Foundation for Suicide Prevention (Grant No. SRG-1-141-18 [to TTY]); by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund (to TTY); by the NIMH (Grant No. R01MH085734 [to TTY]); and by the Brain and Behavior Research Foundation (formerly NARSAD) (to TTY). Funding Information: This work was supported by a personal Veni grant to MH from the Netherlands Organization for Scientific Research (NWO, Grant No. 91619115 [to MH]) and European Community’s Horizon 2020 Programme (H2020/2014 – 2020) (Grant Agreements Nos. 667302 [CoCA], 728018 [Eat2beNICE], and 847879 [PRIME] [to BF]). JBu has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon 2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon 2020–supported programme CANDY (Grant No. 847818 [to JBu]). This work is supported by Grant No. NIA T32AG058507 and NIH Grant No. U54EB020403 from the Big Data to Knowledge (BD2K) Program (to CRKC). ENIGMA MDD work is supported by NIH (Grant Nos. U54 EB020403 [to PT], R01 MH116147 [to PT], and R01 MH117601 [to NJ and LS]). LS was supported by an NHMRC Career Development Fellowship (Grant No. 1140764). This work was supported by the National Center for Research Resources at the NIH (Grant Nos. NIH 1 U24 RR021992 [Function Biomedical Informatics Research Network], NIH 1 U24 RR025736-01 [Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org ]). TGMvE is supported by ENIGMA’s NIH BD2K initiative (Grant No. U54 EB020403), ENIGMA Sex Differences (Grant No. R01MH116147), and ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits (Grant No. R01MH121246). This work was supported by the NIH (Grant No. R01MH121246 [to JT, Calhoun, and TGMvE]). This work was supported in part by NIH (Grant No. U54 EB020403 [to PT]). Funding Information: VA, HJB, KD, DG, and WH express gratitude to all participants of the Münster Neuroimaging Study. EV and RC acknowledge the support of the Spanish Ministry of Science and Innovation and FEDER. PTM and CPa thank C. Loughland, the ASRB Manager, and acknowledges the help of Jason Bridge for ASRB database queries. Funding Information: CAr has been a consultant to or has received honoraria or grants from Acadia, Angelini, Boehringer, Gedeon Richter, Janssen-Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Ethiopia, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. TB served in an advisory or consultancy role for ADHS digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda; received conference support or speaker’s fees from Medice and Takeda; and received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. This work is unrelated to these relationships. DB serves as an unpaid scientific consultant for an EU-funded neurofeedback trial. DC served on the advisory board or speaker for Takeda, Medice, Novartis, and Sunovian, unrelated to this work. HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen-Cilag as well as research funding from Fresenius Medical Care. EHG has received lecture honoraria from Takeda and Sandoz. NJ is MPI of a research grant from Biogen Inc. for work unrelated to the contents of this article. ML has received lecture honoraria from Lundbeck. DHM serves as a consultant for Boehringer Ingelheim, Cadent Therapeutics, Syndisi, and Recognify. CPa has received honoraria for talks at educational meetings and has served on an advisory board for Lundbeck, Australia Pty Ltd. KR reports a grant from Takeda Pharmaceuticals and consultancy fees from Lundbeck. EV has received grants and served as consultant, advisor, or CME speaker for the following entities (unrelated to the present work): AB-Biotics, AbbVie, Aimentia, Angelini, Celon, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH, (Research), GlaxoSmithKline, Janssen, Lundbeck, Organon, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. BF has received educational speaking fees from Medice GmbH. JBu has been in the past 3 years a consultant to, member of advisory board of, and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. CRKC has received partial research support from Biogen, Inc for work unrelated to the topic of this article. OAA has served as a consultant to HealthLytix and received speaker’s honoraria from Ludbeck and Sunovion. FXC has served in the past on a BOL Pharma scientific advisory board, unrelated to this work. PT received partial funding support from Biogen, Inc for research unrelated to this article. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2022 Society of Biological Psychiatry
PY - 2022/8/15
Y1 - 2022/8/15
N2 - BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
AB - BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
KW - Attention Deficit Disorder with Hyperactivity
KW - Autism Spectrum Disorder/genetics
KW - Bipolar Disorder
KW - Cerebral Cortex
KW - Child
KW - Depressive Disorder, Major/pathology
KW - Female
KW - Humans
KW - Infant, Newborn
KW - Magnetic Resonance Imaging/methods
KW - Pregnancy
KW - Premature Birth/pathology
UR - http://www.scopus.com/inward/record.url?scp=85129809360&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2022.02.959
DO - 10.1016/j.biopsych.2022.02.959
M3 - Journal article
C2 - 35489875
SN - 0006-3223
VL - 92
SP - 299
EP - 313
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 4
ER -