Accelerated Cortical Thinning in Schizophrenia is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders.
Journal: Biological psychiatry
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Affiliated Institutions:
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain. Electronic address: javier.gonzalez@iisgm.com.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain.
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. Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain.
Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Galicia, Spain.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Department of Psychiatry, University of Cambridge UK; Department of Medical Physiology and Biophysics, Instituto de Biomedicina de Sevilla (IBiS), HUVR/CSIC/Universidad de Sevilla/CIBERSAM, ISCIII, Sevilla, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Faculty of Medicine and Health Sciences - Psychiatry, Universidad de Oviedo, ISPA, INEUROPA. Oviedo, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; BIOARABA Health Research Institute, OSI Araba, University Hospital, University of the Basque Country, Vitoria, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Hospital Universitario Virgen del Rocío, Department of Psychiatry, Universidad de Sevilla, Sevilla, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Hospital Universitari Institut Pere Mata, Institut d'Investigació Sanitària Pere Virgili-CERCA, Universitat Rovira i Virgili, Reus, Spain.
Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain; Unidad de Neurobiología, Instituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de València,Valencia, Spain.
CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Unidad de Neurobiología, Instituto de Biotecnología y Biomedicina (BIOTECMED), Universitat de València,Valencia, Spain; Department of Genetics, Universitat de València, Campus of Burjassot, Valencia, Spain.
Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
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.
Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands; Altrecht Mental Health Institute, Altrecht Science, Utrecht, The Netherlands.
MRC Centre for Neuropsychiatric Genetics and Genomics and Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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, United States.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Department of Psychiatry, UMCU Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract summary
Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the lifespan. 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.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 to healthy controls from a large longitudinal sample (N = 169 and N = 298, aged 16-70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. We finally explored the functional and genetic underpinnings of the genes most contributing to accelerated thinning.We described a global pattern of accelerated cortical thinning in individuals with schizophrenia compared to healthy controls. Genes underexpressed in cortical regions exhibiting 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.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.
Authors & Co-authors:
González-Peñas
Alloza
Brouwer
Díaz-Caneja
Costas
González-Lois
Gallego
de Hoyos
Gurriarán
Andreu-Bernabeu
Romero-García
Fañanas
Bobes
Pinto
Crespo-Facorro
Martorell
Arrojo
Vilella
Guitiérrez-Zotes
Perez-Rando
Moltó
Buimer
van Haren
Cahn
O'Donovan
Kahn
Arango
Pol
Janssen
Schnack
Study Outcome
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