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

Laura S. van Velzen*, Sinead Kelly, Dmitry Isaev, Andre Aleman, Lyubomir I. Aftanas, Jochen Bauer, Bernhard T. Baune, Ivan V. Brak, Angela Carballedo, Colm G. Connolly, Baptiste Couvy-Duchesne, Kathryn R. Cullen, Konstantin V. Danilenko, Udo Dannlowski, Verena Enneking, Elena Filimonova, Katharina Förster, Thomas Frodl, Ian H. Gotlib, Nynke A. GroenewoldDominik Grotegerd, Mathew A. Harris, Sean N. Hatton, Emma L. Hawkins, Ian B. Hickie, Tiffany C. Ho, Andreas Jansen, Tilo Kircher, Bonnie Klimes-Dougan, Peter Kochunov, Axel Krug, Jim Lagopoulos, Renick Lee, Tristram A. Lett, Meng Li, Frank P. MacMaster, Nicholas G. Martin, Andrew M. McIntosh, Quinn McLellan, Susanne Meinert, Igor Nenadić, Evgeny Osipov, Brenda W.J.H. Penninx, Maria J. Portella, Jonathan Repple, Annerine Roos, Matthew D. Sacchet, Philipp G. Sämann, Robert Vermeiren, Dick J. Veltman, ENIGMA-MDD Consortium, Xueyi Shen, Knut Schnell, Kang Sim, Dan J. Stein, Henrik Walter, Heather C. Whalley, Tony T. Yang, Paul M. Thompson, Neda Jahanshad, L Schmaal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1511-1525
Number of pages15
JournalMolecular Psychiatry
Issue number7
Early online date1 Jan 2019
Publication statusPublished - 1 Jul 2020

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