White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group.

Journal: Molecular psychiatry

Volume: 25

Issue: 7

Year of Publication: 2021

Affiliated Institutions:  Department of Psychiatry, Amsterdam UMC, The Netherlands. laurasvanvelzen@gmail.com. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. Cognitive Neuroscience Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FSSBI "Scientific Research Institute of Physiology & Basic Medicine", Laboratory of Affective, Cognitive & Translational Neuroscience, Novosibirsk, Russia. University of Münster, Institute of Clinical Radiology, Münster, Germany. Department of Psychiatry, University of Münster, Münster, Germany. Department of Psychiatry and Trinity Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Department of Psychiatry, University of California, San Francisco, CA, USA. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. Department of Psychiatry and Behavioral Sciences, The University of Minnesota, Minneapolis, MN, USA. Department of Psychology, Stanford University, Stanford, CA, USA. Department of Psychiatry, University of Cape Town, Cape Town, South Africa. Division of Psychiatry, University of Edinburgh, Edinburgh, UK. Youth Mental Health Team, Brain and Mind Centre, University of Sydney, Camperdown, Australia. Department of Psychiatry, University of Marburg, Marburg, Germany. Department of Psychology, The University of Minnesota, Minneapolis, MN, USA. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Sunshine Coast Mind and Neuroscience-Thompson Institute, Birtinya, QLD, Australia. Research Division, Institute of Mental Health, Singapore, Singapore. Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy CCM, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Department of Neurology, University of Magdeburg, Magdeburg, Germany. Psychiatry and Paediatrics, University of Calgary, Calgary, Canada. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. Department of Neuroscience, University of Calgary, Calgary, Canada. Lab. of Experimental & Translational Neuroscience, Novosibirsk State University, Novosibirsk, Russia. Department of Psychiatry, Amsterdam UMC, The Netherlands. Department of Psychiatry, Institute of Biomedical Research Sant Pau, Barcelona, Spain. SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA, USA. Max Planck Institute of Psychiatry, Munich, Germany. Department of Psychiatry, University of Heidelberg, Heidelberg, Germany. West Region and Research Division, Institute of Mental Health, Singapore, Singapore. SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, South Africa. Mental Health Research Center, Moscow, Russia. Department of Psychiatry and Psychotherapy, Otto von Guericke University, Madgeburg, Germany. Curium-LUMC Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. Instituto ITACA, Universitat Politècnica de València, València, Spain. Department of Psychiatry and Psychotherapy, University of Tübingen, Tubingen, Germany. Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.

Abstract summary 

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

Authors & Co-authors:  van Velzen Laura S LS Kelly Sinead S Isaev Dmitry D Aleman Andre A Aftanas Lyubomir I LI Bauer Jochen J Baune Bernhard T BT Brak Ivan V IV Carballedo Angela A Connolly Colm G CG Couvy-Duchesne Baptiste B Cullen Kathryn R KR Danilenko Konstantin V KV Dannlowski Udo U Enneking Verena V Filimonova Elena E Förster Katharina K Frodl Thomas T Gotlib Ian H IH Groenewold Nynke A NA Grotegerd Dominik D Harris Mathew A MA Hatton Sean N SN Hawkins Emma L EL Hickie Ian B IB Ho Tiffany C TC Jansen Andreas A Kircher Tilo T Klimes-Dougan Bonnie B Kochunov Peter P Krug Axel A Lagopoulos Jim J Lee Renick R Lett Tristram A TA Li Meng M MacMaster Frank P FP Martin Nicholas G NG McIntosh Andrew M AM McLellan Quinn Q Meinert Susanne S Nenadić Igor I Osipov Evgeny E Penninx Brenda W J H BWJH Portella Maria J MJ Repple Jonathan J Roos Annerine A Sacchet Matthew D MD Sämann Philipp G PG Schnell Knut K Shen Xueyi X Sim Kang K Stein Dan J DJ van Tol Marie-Jose MJ Tomyshev Alexander S AS Tozzi Leonardo L Veer Ilya M IM Vermeiren Robert R Vives-Gilabert Yolanda Y Walter Henrik H Walter Martin M van der Wee Nic J A NJA van der Werff Steven J A SJA Schreiner Melinda Westlund MW Whalley Heather C HC Wright Margaret J MJ Yang Tony T TT Zhu Alyssa A Veltman Dick J DJ Thompson Paul M PM Jahanshad Neda N Schmaal Lianne L

Study Outcome 

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Statistics
Citations :  Kessler RC, Angermeyer M, Anthony JC, DE Graaf R, Demyttenaere K, Gasquet I, et al. Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry. 2007;6:168–76.
Authors :  71
Identifiers
Doi : 10.1038/s41380-019-0477-2
SSN : 1476-5578
Study Population
Male,Female
Mesh Terms
Adult
Other Terms
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
England