Neuroimage: Reports (Dec 2022)
A large-scale ENIGMA multisite replication study of brain age in depression
- Laura K.M. Han,
- Richard Dinga,
- Ramona Leenings,
- Tim Hahn,
- James H. Cole,
- Lyubomir I. Aftanas,
- Alyssa R. Amod,
- Bianca Besteher,
- Romain Colle,
- Emmanuelle Corruble,
- Baptiste Couvy-Duchesne,
- Konstantin V. Danilenko,
- Paola Fuentes-Claramonte,
- Ali Saffet Gonul,
- Ian H. Gotlib,
- Roberto Goya-Maldonado,
- Nynke A. Groenewold,
- Paul Hamilton,
- Naho Ichikawa,
- Jonathan C. Ipser,
- Eri Itai,
- Sheri-Michelle Koopowitz,
- Meng Li,
- Go Okada,
- Yasumasa Okamoto,
- Olga S. Churikova,
- Evgeny A. Osipov,
- Brenda W.J.H. Penninx,
- Edith Pomarol-Clotet,
- Elena Rodríguez-Cano,
- Matthew D. Sacchet,
- Hotaka Shinzato,
- Kang Sim,
- Dan J. Stein,
- Aslihan Uyar-Demir,
- Dick J. Veltman,
- Lianne Schmaal
Affiliations
- Laura K.M. Han
- Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia; Orygen, Parkville, VIC, Australia; Corresponding author. University of Melbourne, 35 Poplar road, 3052 Parkville, VIC, Australia.
- Richard Dinga
- Department of Cognitive Science & Artificial Intelligence, Tilburg University, Tilburg, Netherlands
- Ramona Leenings
- Institute for Translational Psychiatry, University of Münster, Münster, Germany; Faculty of Mathematics and Computer Science, University of Münster, Münster, Germany
- Tim Hahn
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- James H. Cole
- Centre for Medical Image Computing, Department of Computer Science, University College London, United Kingdom; Dementia Research Centre, Queen Square Institute of Neurology, University College London, United Kingdom
- Lyubomir I. Aftanas
- Scientific Research Institute of Neuroscience and Medicine, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia
- Alyssa R. Amod
- Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, South Africa
- Bianca Besteher
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
- Romain Colle
- Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Mood Center Paris Saclay, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France; MOODS Team, INSERM 1018, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Le Kremlin Bicêtre, F-94275, France
- Emmanuelle Corruble
- Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Mood Center Paris Saclay, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France; MOODS Team, INSERM 1018, CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Le Kremlin Bicêtre, F-94275, France
- Baptiste Couvy-Duchesne
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, CNRS, Inria, Inserm, AP-HP, Hôpital de La Pitié Salpêtrière, F-75013, Paris, France; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia
- Konstantin V. Danilenko
- Scientific Research Institute of Neuroscience and Medicine, Novosibirsk, Russia
- Paola Fuentes-Claramonte
- FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain; CIBERSAM, Barcelona, Spain
- Ali Saffet Gonul
- SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey
- Ian H. Gotlib
- Department of Psychology, Stanford University, Stanford, CA, USA
- Roberto Goya-Maldonado
- Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen, Göttingen, Germany
- Nynke A. Groenewold
- Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, South Africa
- Paul Hamilton
- Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Sweden; Center for Medical Image Science and Visualization, Department of Biomedical and Clinical Sciences, Linköping University, Sweden
- Naho Ichikawa
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Deloitte Analytics R&D, Deloitte Touche Tohmatsu LLC, Tokyo, Japan
- Jonathan C. Ipser
- Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, South Africa
- Eri Itai
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Sheri-Michelle Koopowitz
- Department of Psychiatry & Mental Health, Neuroscience Institute, University of Cape Town, South Africa
- Meng Li
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
- Go Okada
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Yasumasa Okamoto
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Olga S. Churikova
- Scientific Research Institute of Neuroscience and Medicine, Novosibirsk, Russia
- Evgeny A. Osipov
- Novosibirsk State University, Novosibirsk, Russia
- Brenda W.J.H. Penninx
- Amsterdam UMC, Location Vrije Universiteit, Department of Psychiatry and Amsterdam Neuroscience, Amsterdam, the Netherlands
- Edith Pomarol-Clotet
- FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain; CIBERSAM, Barcelona, Spain
- Elena Rodríguez-Cano
- FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain; CIBERSAM, Barcelona, Spain
- Matthew D. Sacchet
- Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Hotaka Shinzato
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Kang Sim
- West Region, Institute of Mental Health, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Dan J. Stein
- SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa
- Aslihan Uyar-Demir
- SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey
- Dick J. Veltman
- Amsterdam UMC, Location Vrije Universiteit, Department of Psychiatry and Amsterdam Neuroscience, Amsterdam, the Netherlands
- Lianne Schmaal
- Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia; Orygen, Parkville, VIC, Australia
- Journal volume & issue
-
Vol. 2,
no. 4
p. 100149
Abstract
Background: Several studies have evaluated whether depressed persons have older appearing brains than their nondepressed peers. However, the estimated neuroimaging-derived “brain age gap” has varied from study to study, likely driven by differences in training and testing sample (size), age range, and used modality/features. To validate our previously developed ENIGMA brain age model and the identified brain age gap, we aim to replicate the presence and effect size estimate previously found in the largest study in depression to date (N = 2126 controls & N = 2675 cases; +1.08 years [SE 0.22], Cohen's d = 0.14, 95% CI: 0.08–0.20), in independent cohorts that were not part of the original study. Methods: A previously trained brain age model (www.photon-ai.com/enigma_brainage) based on 77 FreeSurfer brain regions of interest was used to obtain unbiased brain age predictions in 751 controls and 766 persons with depression (18–75 years) from 13 new cohorts collected from 20 different scanners. Meta-regressions were used to examine potential moderating effects of basic cohort characteristics (e.g., clinical and scan technical) on the brain age gap. Results: Our ENIGMA MDD brain age model generalized reasonably well to controls from the new cohorts (predicted age vs. age: r = 0.73, R2 = 0.47, MAE = 7.50 years), although the performance varied from cohort to cohort. In these new cohorts, on average, depressed persons showed a significantly higher brain age gap of +1 year (SE 0.35) (Cohen's d = 0.15, 95% CI: 0.05–0.25) compared with controls, highly similar to our previous finding. Significant moderating effects of FreeSurfer version 6.0 (d = 0.41, p = 0.007) and Philips scanner vendor (d = 0.50, p 3400 patients and >2800 controls worldwide show reliable but subtle effects of brain aging in adult depression. Future studies are needed to identify factors that may further explain the brain age gap variance between cohorts.
