Scientific article
Meta-analysis
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Brain ageing in schizophrenia : evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

ContributorsConstantinides, Constantinosorcid; Han, Laura K Morcid; Alloza, Claraorcid; Antonucci, Linda Antonella; Arango, Celsoorcid; Ayesa-Arriola, Rosaorcid; Banaj, Nerisa; Bertolino, Alessandro; Borgwardt, Stefanorcid; Bruggemann, Jason; Bustillo, Juanorcid; Bykhovski, Olegorcid; Calhoun, Vinceorcid; Carr, Vaughanorcid; Catts, Stanley; Chung, Young-Chul; Crespo-Facorro, Benedictoorcid; Díaz-Caneja, Covadonga Morcid; Donohoe, Garyorcid; Plessis, Stefan Du; Edmond, Jesse; Ehrlich, Stefanorcid; Emsley, Robin; Eyler, Lisa T; Fuentes-Claramonte, Paolaorcid; Georgiadis, Foivos; Green, Melissaorcid; Guerrero-Pedraza, Amalia; Ha, Minji; Hahn, Timorcid; Henskens, Frans Aorcid; Holleran, Laurena; Homan, Stephanie; Homan, Philipporcid; Jahanshad, Neda; Janssen, Joost; Ji, Ellenorcid; Kaiser, Stefanorcid; Kaleda, Vasily; Kim, Minahorcid; Kim, Woo-Sung; Kirschner, Matthiasorcid; Kochunov, Peter; Kwak, Yoo Bin; Kwon, Jun Sooorcid; Lebedeva, Irina; Liu, Jingyuorcid; Mitchie, Patriciaorcid; Michielse, Stijnorcid; Mothersill, Davidorcid; Mowry, Bryanorcid; De la Foz, Víctor Ortiz-Garcíaorcid; Pantelis, Christosorcid; Pergola, Giulioorcid; Piras, Fabrizioorcid; Pomarol-Clotet, Edithorcid; Preda, Adrianorcid; Quidé, Yannorcid; Rasser, Paul E; Rootes-Murdy, Kelly; Salvador, Raymondorcid; Sangiuliano, Marina; Sarró, Salvadororcid; Schall, Ulrich; Schmidt, Andréorcid; Scott, Rodney Jorcid; Selvaggi, Pierluigiorcid; Sim, Kang; Skoch, Antoninorcid; Spalletta, Gianfrancoorcid; Spaniel, Filiporcid; Thomopoulos, Sophia I; Tomecek, Davidorcid; Tomyshev, Alexander S; Tordesillas-Gutiérrez, Diana; Van Amelsvoort, Therese; Vázquez-Bourgon, Javierorcid; Vecchio, Danielaorcid; Voineskos, Aristotleorcid; Weickert, Cynthia S; Weickert, Thomasorcid; Thompson, Paul Morcid; Schmaal, Lianneorcid; Van Erp, Theo G Morcid; Turner, Jessicaorcid; Cole, James Horcid; Dima, Danaiorcid; Walton, Estherorcid; ENIGMA Schizophrenia Consortium
Published inMolecular psychiatry, vol. 28, no. 3, p. 1201-1209
Publication date2023-03
First online date2022-12-09
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 +3.55 years (95% CI: 2.91, 4.19; I2  = 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.

Keywords
  • Adult
  • Humans
  • Male
  • Adolescent
  • Young Adult
  • Middle Aged
  • Aged
  • Female
  • Prospective Studies
  • Schizophrenia
  • Magnetic Resonance Imaging
  • Brain / pathology
  • Aging
Funding
Citation (ISO format)
CONSTANTINIDES, Constantinos et al. Brain ageing in schizophrenia : evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium. In: Molecular psychiatry, 2023, vol. 28, n° 3, p. 1201–1209. doi: 10.1038/s41380-022-01897-w
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Additional URL for this publicationhttps://www.nature.com/articles/s41380-022-01897-w
Journal ISSN1359-4184
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