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Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.


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.

SUBMITTER: Constantinides C 

PROVIDER: S-EPMC10005935 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Constantinides Constantinos C   Han Laura K M LKM   Alloza Clara C   Antonucci Linda Antonella LA   Arango Celso C   Ayesa-Arriola Rosa R   Banaj Nerisa N   Bertolino Alessandro A   Borgwardt Stefan S   Bruggemann Jason J   Bustillo Juan J   Bykhovski Oleg O   Calhoun Vince V   Carr Vaughan V   Catts Stanley S   Chung Young-Chul YC   Crespo-Facorro Benedicto B   Díaz-Caneja Covadonga M CM   Donohoe Gary G   Plessis Stefan Du SD   Edmond Jesse J   Ehrlich Stefan S   Emsley Robin R   Eyler Lisa T LT   Fuentes-Claramonte Paola P   Georgiadis Foivos F   Green Melissa M   Guerrero-Pedraza Amalia A   Ha Minji M   Hahn Tim T   Henskens Frans A FA   Holleran Laurena L   Homan Stephanie S   Homan Philipp P   Jahanshad Neda N   Janssen Joost J   Ji Ellen E   Kaiser Stefan S   Kaleda Vasily V   Kim Minah M   Kim Woo-Sung WS   Kirschner Matthias M   Kochunov Peter P   Kwak Yoo Bin YB   Kwon Jun Soo JS   Lebedeva Irina I   Liu Jingyu J   Mitchie Patricia P   Michielse Stijn S   Mothersill David D   Mowry Bryan B   de la Foz Víctor Ortiz-García VO   Pantelis Christos C   Pergola Giulio G   Piras Fabrizio F   Pomarol-Clotet Edith E   Preda Adrian A   Quidé Yann Y   Rasser Paul E PE   Rootes-Murdy Kelly K   Salvador Raymond R   Sangiuliano Marina M   Sarró Salvador S   Schall Ulrich U   Schmidt André A   Scott Rodney J RJ   Selvaggi Pierluigi P   Sim Kang K   Skoch Antonin A   Spalletta Gianfranco G   Spaniel Filip F   Thomopoulos Sophia I SI   Tomecek David D   Tomyshev Alexander S AS   Tordesillas-Gutiérrez Diana D   van Amelsvoort Therese T   Vázquez-Bourgon Javier J   Vecchio Daniela D   Voineskos Aristotle A   Weickert Cynthia S CS   Weickert Thomas T   Thompson Paul M PM   Schmaal Lianne L   van Erp Theo G M TGM   Turner Jessica J   Cole James H JH   Dima Danai D   Walton Esther E  

Molecular psychiatry 20221209 3


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%  ...[more]

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