학술논문
Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium
Document Type
Original Paper
Author
Constantinides, Constantinos; Han, Laura K. M.; Alloza, Clara; Antonucci, Linda Antonella; Arango, Celso; Ayesa-Arriola, Rosa; Banaj, Nerisa; Bertolino, Alessandro; Borgwardt, Stefan; Bruggemann, Jason; Bustillo, Juan; Bykhovski, Oleg; Calhoun, Vince; Carr, Vaughan; Catts, Stanley; Chung, Young-Chul; Crespo-Facorro, Benedicto; Díaz-Caneja, Covadonga M.; Donohoe, Gary; Plessis, Stefan Du; Edmond, Jesse; Ehrlich, Stefan; Emsley, Robin; Eyler, Lisa T.; Fuentes-Claramonte, Paola; Georgiadis, Foivos; Green, Melissa; Guerrero-Pedraza, Amalia; Ha, Minji; Hahn, Tim; Henskens, Frans A.; Holleran, Laurena; Homan, Stephanie; Homan, Philipp; Jahanshad, Neda; Janssen, Joost; Ji, Ellen; Kaiser, Stefan; Kaleda, Vasily; Kim, Minah; Kim, Woo-Sung; Kirschner, Matthias; Kochunov, Peter; Kwak, Yoo Bin; Kwon, Jun Soo; Lebedeva, Irina; Liu, Jingyu; Mitchie, Patricia; Michielse, Stijn; Mothersill, David; Mowry, Bryan; de la Foz, Víctor Ortiz-García; Pantelis, Christos; Pergola, Giulio; Piras, Fabrizio; Pomarol-Clotet, Edith; Preda, Adrian; Quidé, Yann; Rasser, Paul E.; Rootes-Murdy, Kelly; Salvador, Raymond; Sangiuliano, Marina; Sarró, Salvador; Schall, Ulrich; Schmidt, André; Scott, Rodney J.; Selvaggi, Pierluigi; Sim, Kang; Skoch, Antonin; Spalletta, Gianfranco; Spaniel, Filip; Thomopoulos, Sophia I.; Tomecek, David; Tomyshev, Alexander S.; Tordesillas-Gutiérrez, Diana; van Amelsvoort, Therese; Vázquez-Bourgon, Javier; Vecchio, Daniela; Voineskos, Aristotle; Weickert, Cynthia S.; Weickert, Thomas; Thompson, Paul M.; Schmaal, Lianne; van Erp, Theo G. M.; Turner, Jessica; Cole, James H.; Dima, Danai; Walton, Esther
Source
Molecular Psychiatry. 28(3):1201-1209
Subject
Language
English
ISSN
1359-4184
1476-5578
1476-5578
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.