학술논문
Accelerated Cortical Thinning in Schizophrenia Is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders.
Document Type
Academic Journal
Author
González-Peñas J; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain. Electronic address: javier.gonzalez@iisgm.com.; Alloza C; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain.; Brouwer R; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Díaz-Caneja CM; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain.; Costas J; Instituto de Investigación Sanitària de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde, Santiago de Compostela, Galicia, Spain.; González-Lois N; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain.; Gallego AG; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain.; de Hoyos L; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain.; Gurriarán X; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain.; Andreu-Bernabeu Á; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain.; Romero-García R; Department of Medical Physiology and Biophysics, Instituto de Biomedicina de Sevilla, HUVR/CSIC/Universidad de Sevilla/CIBERSAM, Instituto de Salud Carlos III, Sevilla, Spain; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.; Fañanás L; CIBERSAM, Madrid, Spain; Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain.; Bobes J; CIBERSAM, Madrid, Spain; Faculty of Medicine and Health Sciences-Psychiatry, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, Instituto de Neurociencias del Principado de Asturias, Oviedo, Spain.; González-Pinto A; CIBERSAM, Madrid, Spain; BIOARABA Health Research Institute, Organización Sanitaria Integrada Araba, University Hospital, University of the Basque Country, Vitoria, Spain.; Crespo-Facorro B; CIBERSAM, Madrid, Spain; Hospital Universitario Virgen del Rocío, Department of Psychiatry, Universidad de Sevilla, Sevilla, Spain.; Martorell L; CIBERSAM, Madrid, Spain; Hospital Universitari Institut Pere Mata, Institut d'Investigació Sanitària Pere Virgili-Centres de Recerca de Catalunya, Universitat Rovira i Virgili, Reus, Spain.; Arrojo M; Instituto de Investigación Sanitària de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde, Santiago de Compostela, Galicia, Spain.; Vilella E; CIBERSAM, Madrid, Spain; Hospital Universitari Institut Pere Mata, Institut d'Investigació Sanitària Pere Virgili-Centres de Recerca de Catalunya, Universitat Rovira i Virgili, Reus, Spain.; Gutiérrez-Zotes A; CIBERSAM, Madrid, Spain; Hospital Universitari Institut Pere Mata, Institut d'Investigació Sanitària Pere Virgili-Centres de Recerca de Catalunya, Universitat Rovira i Virgili, Reus, Spain.; Perez-Rando M; Fundación Investigación Hospital Clínico de València, Fundación Investigación Hospital Clínico de Valencia, València, Spain; Unidad de Neurobiología, Instituto de Biotecnología y Biomedicina, Universitat de València, València, Spain.; Moltó MD; CIBERSAM, Madrid, Spain; Unidad de Neurobiología, Instituto de Biotecnología y Biomedicina, Universitat de València, València, Spain; Department of Genetics, Universitat de València, Campus of Burjassot, València, Spain.; Buimer E; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.; van Haren N; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre, Rotterdam, the Netherlands.; Cahn W; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands; Altrecht Mental Health Institute, Altrecht Science, Utrecht, the Netherlands.; O'Donovan M; Medical Research Council for Neuropsychiatric Genetics and Genomics and Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Kahn RS; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.; Arango C; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain.; Pol HH; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.; Janssen J; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitària Gregorio Marañón, Madrid, Spain; CIBERSAM, Madrid, Spain; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.; Schnack H; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified.
Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (ncases = 169 and n controls = 298, ages 16-70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning.
Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences.
Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia.
(Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Methods: We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample (n
Results: We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences.
Conclusions: Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia.
(Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)