TY - JOUR
T1 - Brain ageing in schizophrenia
T2 - evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium
AU - Constantinides, Constantinos
AU - Han, Laura K M
AU - Alloza, Clara
AU - Antonucci, Linda Antonella
AU - Arango, Celso
AU - Ayesa-Arriola, Rosa
AU - Banaj, Nerisa
AU - Bertolino, Alessandro
AU - Borgwardt, Stefan
AU - Bruggemann, Jason
AU - Bustillo, Juan
AU - Bykhovski, Oleg
AU - Calhoun, Vince
AU - Carr, Vaughan
AU - Catts, Stanley
AU - Chung, Young-Chul
AU - Crespo-Facorro, Benedicto
AU - Díaz-Caneja, Covadonga M
AU - Donohoe, Gary
AU - Plessis, Stefan Du
AU - Edmond, Jesse
AU - Ehrlich, Stefan
AU - Emsley, Robin
AU - Eyler, Lisa T
AU - Fuentes-Claramonte, Paola
AU - Georgiadis, Foivos
AU - Green, Melissa
AU - Guerrero-Pedraza, Amalia
AU - Ha, Minji
AU - Hahn, Tim
AU - Henskens, Frans A
AU - Holleran, Laurena
AU - Homan, Stephanie
AU - Homan, Philipp
AU - Jahanshad, Neda
AU - Janssen, Joost
AU - Ji, Ellen
AU - Kaiser, Stefan
AU - Kaleda, Vasily
AU - Kim, Minah
AU - Kim, Woo-Sung
AU - Kirschner, Matthias
AU - Kochunov, Peter
AU - Kwak, Yoo Bin
AU - Kwon, Jun Soo
AU - Lebedeva, Irina
AU - Liu, Jingyu
AU - Mitchie, Patricia
AU - Michielse, Stijn
AU - van Amelsvoort, Therese
AU - ENIGMA Schizophrenia Consortium
AU - Walton, Esther
N1 - © 2022. The Author(s).
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
U2 - 10.1038/s41380-022-01897-w
DO - 10.1038/s41380-022-01897-w
M3 - Article
C2 - 36494461
SN - 1359-4184
VL - 28
SP - 1201
EP - 1209
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 3
ER -