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

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 e...

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Main Authors: van Velzen, Laura S., Kelly, Sinead, Isaev, Dmitry, Aleman, Andre, Aftanas, Lyubomir I, Bauer, Jochen, Baune, Bernhard T., Brak, Ivan V., Carballedo, Angela, Connolly, Colm G., Couvy-Duchesne, Baptiste, Cullen, Kathryn R, Danilenko, Konstantin V, Dannlowski, Udo, Enneking, Verena, Filimonova, Elena, Förster, Katharina, Frodl, Thomas, Gotlib, Ian H., Groenewold, Nynke A., Grotegerd, Dominik, Harris, Mathew A., Hatton, Sean N., Hawkins, Emma L., Hickie, Ian B., Ho, Tiffany C., Jansen, Andreas, Kircher, Tilo, Klimes-Dougan, Bonnie, Kochunov, Peter, Krug, Axel, Lagopoulos, Jim, Lee, Renick, Lett, Tristram A., Li, Meng, MacMaster, Frank P., Martin, Nicholas G., McIntosh, Andrew M., McLellan, Quinn, Meinert, Susanne, Nenadić, Igor, Osipov, Evgeny, Penninx, Brenda W. J. H., Portella, Maria J., Repple, Jonathan, Roos, Annerine, Sacchet, Matthew D., Sämann, Philipp G., Schnell, Knut, Shen, Xueyi, Sim, Kang, Stein, Dan J., van Tol, Marie-Jose, Tomyshev, Alexander S., Tozzi, Leonardo, Veer, Ilya M., Vermeiren, Robert, Vives-Gilabert, Yolanda, Walter, Henrik, Walter, Martin, van der Wee, Nic J. A., van der Werff, Steven J. A., Schreiner, Melinda Westlund, Whalley, Heather C., Wright, Margaret J., Yang, Tony T., Zhu, Alyssa, Veltman, Dick J., Thompson, Paul M., Jahanshad, Neda, Schmaal, Lianne
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
Subjects:
Online Access:https://hdl.handle.net/10356/148925
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-148925
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Depression
Neuroscience
spellingShingle Science::Medicine
Depression
Neuroscience
van Velzen, Laura S.
Kelly, Sinead
Isaev, Dmitry
Aleman, Andre
Aftanas, Lyubomir I
Bauer, Jochen
Baune, Bernhard T.
Brak, Ivan V.
Carballedo, Angela
Connolly, Colm G.
Couvy-Duchesne, Baptiste
Cullen, Kathryn R
Danilenko, Konstantin V
Dannlowski, Udo
Enneking, Verena
Filimonova, Elena
Förster, Katharina
Frodl, Thomas
Gotlib, Ian H.
Groenewold, Nynke A.
Grotegerd, Dominik
Harris, Mathew A.
Hatton, Sean N.
Hawkins, Emma L.
Hickie, Ian B.
Ho, Tiffany C.
Jansen, Andreas
Kircher, Tilo
Klimes-Dougan, Bonnie
Kochunov, Peter
Krug, Axel
Lagopoulos, Jim
Lee, Renick
Lett, Tristram A.
Li, Meng
MacMaster, Frank P.
Martin, Nicholas G.
McIntosh, Andrew M.
McLellan, Quinn
Meinert, Susanne
Nenadić, Igor
Osipov, Evgeny
Penninx, Brenda W. J. H.
Portella, Maria J.
Repple, Jonathan
Roos, Annerine
Sacchet, Matthew D.
Sämann, Philipp G.
Schnell, Knut
Shen, Xueyi
Sim, Kang
Stein, Dan J.
van Tol, Marie-Jose
Tomyshev, Alexander S.
Tozzi, Leonardo
Veer, Ilya M.
Vermeiren, Robert
Vives-Gilabert, Yolanda
Walter, Henrik
Walter, Martin
van der Wee, Nic J. A.
van der Werff, Steven J. A.
Schreiner, Melinda Westlund
Whalley, Heather C.
Wright, Margaret J.
Yang, Tony T.
Zhu, Alyssa
Veltman, Dick J.
Thompson, Paul M.
Jahanshad, Neda
Schmaal, Lianne
White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
van Velzen, Laura S.
Kelly, Sinead
Isaev, Dmitry
Aleman, Andre
Aftanas, Lyubomir I
Bauer, Jochen
Baune, Bernhard T.
Brak, Ivan V.
Carballedo, Angela
Connolly, Colm G.
Couvy-Duchesne, Baptiste
Cullen, Kathryn R
Danilenko, Konstantin V
Dannlowski, Udo
Enneking, Verena
Filimonova, Elena
Förster, Katharina
Frodl, Thomas
Gotlib, Ian H.
Groenewold, Nynke A.
Grotegerd, Dominik
Harris, Mathew A.
Hatton, Sean N.
Hawkins, Emma L.
Hickie, Ian B.
Ho, Tiffany C.
Jansen, Andreas
Kircher, Tilo
Klimes-Dougan, Bonnie
Kochunov, Peter
Krug, Axel
Lagopoulos, Jim
Lee, Renick
Lett, Tristram A.
Li, Meng
MacMaster, Frank P.
Martin, Nicholas G.
McIntosh, Andrew M.
McLellan, Quinn
Meinert, Susanne
Nenadić, Igor
Osipov, Evgeny
Penninx, Brenda W. J. H.
Portella, Maria J.
Repple, Jonathan
Roos, Annerine
Sacchet, Matthew D.
Sämann, Philipp G.
Schnell, Knut
Shen, Xueyi
Sim, Kang
Stein, Dan J.
van Tol, Marie-Jose
Tomyshev, Alexander S.
Tozzi, Leonardo
Veer, Ilya M.
Vermeiren, Robert
Vives-Gilabert, Yolanda
Walter, Henrik
Walter, Martin
van der Wee, Nic J. A.
van der Werff, Steven J. A.
Schreiner, Melinda Westlund
Whalley, Heather C.
Wright, Margaret J.
Yang, Tony T.
Zhu, Alyssa
Veltman, Dick J.
Thompson, Paul M.
Jahanshad, Neda
Schmaal, Lianne
format Article
author van Velzen, Laura S.
Kelly, Sinead
Isaev, Dmitry
Aleman, Andre
Aftanas, Lyubomir I
Bauer, Jochen
Baune, Bernhard T.
Brak, Ivan V.
Carballedo, Angela
Connolly, Colm G.
Couvy-Duchesne, Baptiste
Cullen, Kathryn R
Danilenko, Konstantin V
Dannlowski, Udo
Enneking, Verena
Filimonova, Elena
Förster, Katharina
Frodl, Thomas
Gotlib, Ian H.
Groenewold, Nynke A.
Grotegerd, Dominik
Harris, Mathew A.
Hatton, Sean N.
Hawkins, Emma L.
Hickie, Ian B.
Ho, Tiffany C.
Jansen, Andreas
Kircher, Tilo
Klimes-Dougan, Bonnie
Kochunov, Peter
Krug, Axel
Lagopoulos, Jim
Lee, Renick
Lett, Tristram A.
Li, Meng
MacMaster, Frank P.
Martin, Nicholas G.
McIntosh, Andrew M.
McLellan, Quinn
Meinert, Susanne
Nenadić, Igor
Osipov, Evgeny
Penninx, Brenda W. J. H.
Portella, Maria J.
Repple, Jonathan
Roos, Annerine
Sacchet, Matthew D.
Sämann, Philipp G.
Schnell, Knut
Shen, Xueyi
Sim, Kang
Stein, Dan J.
van Tol, Marie-Jose
Tomyshev, Alexander S.
Tozzi, Leonardo
Veer, Ilya M.
Vermeiren, Robert
Vives-Gilabert, Yolanda
Walter, Henrik
Walter, Martin
van der Wee, Nic J. A.
van der Werff, Steven J. A.
Schreiner, Melinda Westlund
Whalley, Heather C.
Wright, Margaret J.
Yang, Tony T.
Zhu, Alyssa
Veltman, Dick J.
Thompson, Paul M.
Jahanshad, Neda
Schmaal, Lianne
author_sort van Velzen, Laura S.
title White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
title_short White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
title_full White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
title_fullStr White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
title_full_unstemmed White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group
title_sort white matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the enigma mdd working group
publishDate 2021
url https://hdl.handle.net/10356/148925
_version_ 1759854617478299648
spelling sg-ntu-dr.10356-1489252023-03-05T16:44:02Z White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group van Velzen, Laura S. Kelly, Sinead Isaev, Dmitry Aleman, Andre Aftanas, Lyubomir I Bauer, Jochen Baune, Bernhard T. Brak, Ivan V. Carballedo, Angela Connolly, Colm G. Couvy-Duchesne, Baptiste Cullen, Kathryn R Danilenko, Konstantin V Dannlowski, Udo Enneking, Verena Filimonova, Elena Förster, Katharina Frodl, Thomas Gotlib, Ian H. Groenewold, Nynke A. Grotegerd, Dominik Harris, Mathew A. Hatton, Sean N. Hawkins, Emma L. Hickie, Ian B. Ho, Tiffany C. Jansen, Andreas Kircher, Tilo Klimes-Dougan, Bonnie Kochunov, Peter Krug, Axel Lagopoulos, Jim Lee, Renick Lett, Tristram A. Li, Meng MacMaster, Frank P. Martin, Nicholas G. McIntosh, Andrew M. McLellan, Quinn Meinert, Susanne Nenadić, Igor Osipov, Evgeny Penninx, Brenda W. J. H. Portella, Maria J. Repple, Jonathan Roos, Annerine Sacchet, Matthew D. Sämann, Philipp G. Schnell, Knut Shen, Xueyi Sim, Kang Stein, Dan J. van Tol, Marie-Jose Tomyshev, Alexander S. Tozzi, Leonardo Veer, Ilya M. Vermeiren, Robert Vives-Gilabert, Yolanda Walter, Henrik Walter, Martin van der Wee, Nic J. A. van der Werff, Steven J. A. Schreiner, Melinda Westlund Whalley, Heather C. Wright, Margaret J. Yang, Tony T. Zhu, Alyssa Veltman, Dick J. Thompson, Paul M. Jahanshad, Neda Schmaal, Lianne Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Depression Neuroscience 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. Published version 2021-05-10T07:00:21Z 2021-05-10T07:00:21Z 2019 Journal Article van Velzen, L. S., Kelly, S., Isaev, D., Aleman, A., Aftanas, L. I., Bauer, J., Baune, B. T., Brak, I. V., Carballedo, A., Connolly, C. G., Couvy-Duchesne, B., Cullen, K. R., Danilenko, K. V., Dannlowski, U., Enneking, V., Filimonova, E., Förster, K., Frodl, T., Gotlib, I. H., ...Schmaal, L. (2019). White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group. Molecular Psychiatry, 25(7), 1511-1525. https://dx.doi.org/10.1038/s41380-019-0477-2 1359-4184 0000-0001-6548-426X 0000-0002-5146-0096 0000-0002-4051-3682 0000-0002-1135-4141 0000-0002-0731-9626 0000-0003-4069-8020 0000-0002-0198-4588 0000-0003-3806-2218 0000-0001-7218-7810 0000-0002-9260-5490 0000-0002-9403-6121 0000-0002-2780-3327 0000-0002-4505-8869 0000-0001-7133-4970 0000-0003-4401-8950 https://hdl.handle.net/10356/148925 10.1038/s41380-019-0477-2 31471575 2-s2.0-85072031087 7 25 1511 1525 en Molecular Psychiatry © The Author(s) 2019. This article is published with open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. application/pdf