{"doi":"10.1101/2022.01.10.21267840","title":"Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium","abstract":"Abstract 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 +3.64 years (95% CI: 3.01, 4.26; I 2 = 55.28%) compared to controls, after adjusting for age and sex (Cohen’s d = 0.50). 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.","journal":"medRxiv","year":2022,"id":296803,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5918,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109312,"name":"Laura K. M. Han","orcid":"0000-0001-9647-3723","position":1,"is_corresponding":false},{"id":177,"name":"Clara Alloza","orcid":"0000-0002-2092-8055","position":2,"is_corresponding":false},{"id":767187,"name":"Linda A. Antonucci","orcid":"0000-0002-7919-7402","position":3,"is_corresponding":false},{"id":56339,"name":"Celso Arango","orcid":"0000-0003-3382-4754","position":4,"is_corresponding":false},{"id":237617,"name":"Rosa Ayesa‐Arriola","orcid":"0000-0003-0570-5352","position":5,"is_corresponding":false},{"id":236925,"name":"Nerisa Banaj","orcid":"0000-0002-6317-8549","position":6,"is_corresponding":false},{"id":236929,"name":"Alessandro Bertolino","orcid":"0000-0002-1251-1380","position":7,"is_corresponding":false},{"id":40528,"name":"Stefan Borgwardt","orcid":"0000-0002-5792-3987","position":8,"is_corresponding":false},{"id":236918,"name":"Jason Bruggemann","orcid":"0000-0002-9929-0911","position":9,"is_corresponding":false},{"id":233025,"name":"Juan Bustillo","orcid":"0000-0001-8730-8152","position":10,"is_corresponding":false},{"id":846372,"name":"Oleg Bykhovski","orcid":"0000-0001-7571-1120","position":11,"is_corresponding":false},{"id":62327,"name":"Vaughan J. Carr","orcid":"0000-0002-8907-5804","position":12,"is_corresponding":false},{"id":62329,"name":"Stanley V. Catts","orcid":"0000-0002-8313-9555","position":13,"is_corresponding":false},{"id":846373,"name":"Young‐Chul Chung","orcid":"0000-0001-9491-1822","position":14,"is_corresponding":false},{"id":78886,"name":"Benedicto Crespo‐Facorro","orcid":"0000-0003-0033-7132","position":15,"is_corresponding":false},{"id":84132,"name":"Covadonga M. Díaz‐Caneja","orcid":"0000-0001-8538-3175","position":16,"is_corresponding":false},{"id":62347,"name":"Gary Donohoe","orcid":"0000-0003-3037-7426","position":17,"is_corresponding":false},{"id":236930,"name":"Stefan S. du Plessis","orcid":"0000-0003-4617-4367","position":18,"is_corresponding":false},{"id":847310,"name":"Jesse T. Edmond","orcid":null,"position":19,"is_corresponding":false},{"id":107794,"name":"Stefan Ehrlich","orcid":"0000-0003-2132-4445","position":20,"is_corresponding":false},{"id":283009,"name":"Robin Emsley","orcid":"0000-0003-1250-6888","position":21,"is_corresponding":false},{"id":109306,"name":"Lisa T. Eyler","orcid":"0000-0002-7783-8798","position":22,"is_corresponding":false},{"id":260681,"name":"Paola Fuentes‐Claramonte","orcid":"0000-0002-1428-7976","position":23,"is_corresponding":false},{"id":846374,"name":"Foivos Georgiadis","orcid":"0000-0001-8784-9653","position":24,"is_corresponding":false},{"id":107806,"name":"Melissa J. Green","orcid":"0000-0002-9361-4874","position":25,"is_corresponding":false},{"id":846375,"name":"Amalia Guerrero‐Pedraza","orcid":"0000-0001-7567-9407","position":26,"is_corresponding":false},{"id":846376,"name":"Minji Ha","orcid":"0000-0002-9840-6695","position":27,"is_corresponding":false},{"id":235022,"name":"Tim Hahn","orcid":"0000-0001-6541-3795","position":28,"is_corresponding":false},{"id":62369,"name":"Frans Henskens","orcid":"0000-0003-2358-5630","position":29,"is_corresponding":false},{"id":107819,"name":"Laurena Holleran","orcid":"0000-0002-8354-3670","position":30,"is_corresponding":false},{"id":846377,"name":"Stephanie Homan","orcid":"0000-0003-1449-7508","position":31,"is_corresponding":false},{"id":520395,"name":"Philipp Homan","orcid":"0000-0001-9034-148X","position":32,"is_corresponding":false},{"id":107762,"name":"Neda Jahanshad","orcid":"0000-0003-4401-8950","position":33,"is_corresponding":false},{"id":236931,"name":"Joost Janssen","orcid":"0000-0001-7613-2067","position":34,"is_corresponding":false},{"id":612120,"name":"Ellen Ji","orcid":"0000-0003-1527-8868","position":35,"is_corresponding":false},{"id":662920,"name":"Stefan Kaiser","orcid":"0000-0002-3013-2034","position":36,"is_corresponding":false},{"id":236936,"name":"В. Г. Каледа","orcid":"0000-0002-1209-1443","position":37,"is_corresponding":false},{"id":630091,"name":"Minah Kim","orcid":"0000-0001-8668-0817","position":38,"is_corresponding":false},{"id":984101,"name":"Woo‐Sung Kim","orcid":"0000-0003-3404-5576","position":39,"is_corresponding":false},{"id":236937,"name":"Matthias Kirschner","orcid":"0000-0002-9486-1439","position":40,"is_corresponding":false},{"id":227759,"name":"Peter Kochunov","orcid":"0000-0003-3656-4281","position":41,"is_corresponding":false},{"id":630072,"name":"Yoo Bin Kwak","orcid":"0000-0001-6959-495X","position":42,"is_corresponding":false},{"id":109318,"name":"Jun Soo Kwon","orcid":"0000-0002-1060-1462","position":43,"is_corresponding":false},{"id":236935,"name":"И. С. Лебедева","orcid":"0000-0002-0649-6663","position":44,"is_corresponding":false},{"id":301189,"name":"Jingyu Liu","orcid":"0000-0002-1724-7523","position":45,"is_corresponding":false},{"id":847311,"name":"Patricia Mitchie","orcid":null,"position":46,"is_corresponding":false},{"id":466973,"name":"Stijn Michielse","orcid":"0000-0003-3930-8646","position":47,"is_corresponding":false},{"id":289183,"name":"David Mothersill","orcid":"0000-0003-3013-4088","position":48,"is_corresponding":false},{"id":236921,"name":"Bryan Mowry","orcid":"0000-0002-4115-5645","position":49,"is_corresponding":false},{"id":289191,"name":"Víctor Ortiz‐García de la Foz","orcid":"0000-0002-0627-1827","position":50,"is_corresponding":false},{"id":62421,"name":"Christos Pantelis","orcid":"0000-0002-9565-0238","position":51,"is_corresponding":false},{"id":355775,"name":"Giulio Pergola","orcid":"0000-0002-9193-1841","position":52,"is_corresponding":false},{"id":109325,"name":"Fabrizio Piras","orcid":"0000-0003-3566-5494","position":53,"is_corresponding":false},{"id":236926,"name":"Edith Pomarol‐Clotet","orcid":"0000-0002-8159-8563","position":54,"is_corresponding":false},{"id":236942,"name":"Adrian Preda","orcid":"0000-0003-3373-2438","position":55,"is_corresponding":false},{"id":236915,"name":"Yann Quidé","orcid":"0000-0002-8569-7139","position":56,"is_corresponding":false},{"id":236955,"name":"Paul E. Rasser","orcid":"0000-0003-3482-721X","position":57,"is_corresponding":false},{"id":422774,"name":"Kelly Rootes-Murdy","orcid":"0000-0003-2704-2035","position":58,"is_corresponding":false},{"id":259244,"name":"Raymond Salvador","orcid":"0000-0001-5557-1562","position":59,"is_corresponding":false},{"id":847312,"name":"Marina Sangiuliano","orcid":null,"position":60,"is_corresponding":false},{"id":236927,"name":"Salvador Sarró","orcid":"0000-0003-1835-2189","position":61,"is_corresponding":false},{"id":236920,"name":"Ulrich Schall","orcid":"0000-0001-9041-4562","position":62,"is_corresponding":false},{"id":355778,"name":"André Schmidt","orcid":"0000-0001-6055-8397","position":63,"is_corresponding":false},{"id":52321,"name":"Rodney J. Scott","orcid":null,"position":64,"is_corresponding":false},{"id":846379,"name":"Pierluigi Selvaggi","orcid":"0000-0001-9069-0700","position":65,"is_corresponding":false},{"id":62439,"name":"Kang Sim","orcid":"0000-0003-3209-9626","position":66,"is_corresponding":false},{"id":236939,"name":"Antonín Škoch","orcid":"0000-0002-1739-3256","position":67,"is_corresponding":false},{"id":109330,"name":"Gianfranco Spalletta","orcid":"0000-0002-7432-4249","position":68,"is_corresponding":false},{"id":45323,"name":"Filip Španiel","orcid":"0000-0003-3479-696X","position":69,"is_corresponding":false},{"id":107770,"name":"Sophia I. Thomopoulos","orcid":"0000-0002-0046-4070","position":70,"is_corresponding":false},{"id":45322,"name":"David Tomeček","orcid":"0000-0001-7038-0529","position":71,"is_corresponding":false},{"id":236934,"name":"A. S. Tomyshev","orcid":"0000-0001-6688-4329","position":72,"is_corresponding":false},{"id":289182,"name":"Diana Tordesillas‐Gutiérrez","orcid":"0000-0003-1458-3932","position":73,"is_corresponding":false},{"id":236940,"name":"Thérèse van Amelsvoort","orcid":"0000-0003-1135-5133","position":74,"is_corresponding":false},{"id":648142,"name":"Javier Vázquez-Bourgón","orcid":"0000-0002-5478-3376","position":75,"is_corresponding":false},{"id":285890,"name":"Daniela Vecchio","orcid":"0000-0001-8428-7376","position":76,"is_corresponding":false},{"id":230416,"name":"Aristotle N. Voineskos","orcid":"0000-0003-0156-0395","position":77,"is_corresponding":false},{"id":236916,"name":"Cynthia Shannon Weickert","orcid":"0000-0002-4560-0259","position":78,"is_corresponding":false},{"id":236917,"name":"Thomas W. Weickert","orcid":"0000-0002-6408-718X","position":79,"is_corresponding":false},{"id":51712,"name":"Paul M. Thompson","orcid":"0000-0002-4720-8867","position":80,"is_corresponding":false},{"id":240735,"name":"Lianne Schmaal","orcid":"0000-0001-9822-048X","position":81,"is_corresponding":false},{"id":809845,"name":"T.G. van Erp","orcid":null,"position":82,"is_corresponding":false},{"id":90656,"name":"Jessica A. Turner","orcid":"0000-0003-0076-8434","position":83,"is_corresponding":false},{"id":54146,"name":"James H. Cole","orcid":"0000-0003-1908-5588","position":84,"is_corresponding":false},{"id":109365,"name":"Danai Dima","orcid":"0000-0002-2598-0952","position":85,"is_corresponding":false},{"id":109337,"name":"Esther Walton","orcid":"0000-0002-0935-2200","position":86,"is_corresponding":false},{"id":846371,"name":"Constantinos Constantinides","orcid":"0000-0002-0312-9534","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:21.257700Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}