Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.
Journal: Molecular psychiatry
Volume: 28
Issue: 3
Year of Publication: 2023
Affiliated Institutions:
Department of Psychology, University of Bath, Bath, UK.
Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.
Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain.
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
Department of Psychiatry, Psychiatric University Hospital (UPK), University of Basel, Basel, Switzerland.
Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, GA, USA.
School of Medicine, University of Queensland, Herston, QLD, Australia.
Department of Psychiatry, Jeonbuk National University, Medical School, Jeonju, Korea.
Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Psychology, National University of Ireland Galway, Galway, Ireland.
Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Department of Psychology, Georgia State University, Atlanta, GA, USA.
Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Germany.
Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Catalonia, Spain.
Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
Institute for Translational Psychiatry, University of Münster, Münster, Germany.
School of Medicine & Public Health, The University of Newcastle, Newcastle, NSW, Australia.
Psychiatric University Hospital Zurich, Zurich, Switzerland.
Imaging Genetics Center, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
Mental Health Research Center, Moscow, Russia.
Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Computer Science, Georgia State University, Atlanta, GA, USA.
Hunter Medical Research Institute, Newcastle, NSW, Australia.
Department of Neurosurgery, School of Mental Health and Neuroscience, EURON, Maastricht University Medical Centre, Maastricht, The Netherlands.
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Carlton South, VIC, Australia.
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
West Region, Institute of Mental Health, Singapore, Singapore.
National Institute of Mental Health, Klecany, Czech Republic.
Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain.
Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.
Campbell Family Mental Health Research Institute, CAMH, Toronto, Canada.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Psychology, University of Bath, Bath, UK. E.Walton@bath.ac.uk.
Abstract summary
Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
Authors & Co-authors:
Constantinides Constantinos C
Han Laura K M LKM
Alloza Clara C
Antonucci Linda Antonella LA
Arango Celso C
Ayesa-Arriola Rosa R
Banaj Nerisa N
Bertolino Alessandro A
Borgwardt Stefan S
Bruggemann Jason J
Bustillo Juan J
Bykhovski Oleg O
Calhoun Vince V
Carr Vaughan V
Catts Stanley S
Chung Young-Chul YC
Crespo-Facorro Benedicto B
Díaz-Caneja Covadonga M CM
Donohoe Gary G
Plessis Stefan Du SD
Edmond Jesse J
Ehrlich Stefan S
Emsley Robin R
Eyler Lisa T LT
Fuentes-Claramonte Paola P
Georgiadis Foivos F
Green Melissa M
Guerrero-Pedraza Amalia A
Ha Minji M
Hahn Tim T
Henskens Frans A FA
Holleran Laurena L
Homan Stephanie S
Homan Philipp P
Jahanshad Neda N
Janssen Joost J
Ji Ellen E
Kaiser Stefan S
Kaleda Vasily V
Kim Minah M
Kim Woo-Sung WS
Kirschner Matthias M
Kochunov Peter P
Kwak Yoo Bin YB
Kwon Jun Soo JS
Lebedeva Irina I
Liu Jingyu J
Mitchie Patricia P
Michielse Stijn S
Mothersill David D
Mowry Bryan B
de la Foz Víctor Ortiz-García VO
Pantelis Christos C
Pergola Giulio G
Piras Fabrizio F
Pomarol-Clotet Edith E
Preda Adrian A
Quidé Yann Y
Rasser Paul E PE
Rootes-Murdy Kelly K
Salvador Raymond R
Sangiuliano Marina M
Sarró Salvador S
Schall Ulrich U
Schmidt André A
Scott Rodney J RJ
Selvaggi Pierluigi P
Sim Kang K
Skoch Antonin A
Spalletta Gianfranco G
Spaniel Filip F
Thomopoulos Sophia I SI
Tomecek David D
Tomyshev Alexander S AS
Tordesillas-Gutiérrez Diana D
van Amelsvoort Therese T
Vázquez-Bourgon Javier J
Vecchio Daniela D
Voineskos Aristotle A
Weickert Cynthia S CS
Weickert Thomas T
Thompson Paul M PM
Schmaal Lianne L
van Erp Theo G M TGM
Turner Jessica J
Cole James H JH
Dima Danai D
Walton Esther E
Study Outcome
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