Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium
Authors: 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. ,   ENIGMA Schizophrenia Consortium, Ayesa-Arriola Rosa , Du Plessis Stefan , Bin Kwak Yoo , de la Foz Víctor Ortiz-García , van Amelsvoort Therese , van Erp Theo G. M. , Dima Danai , Walton Esther 
Published: December 2022

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.