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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/148925 |
| _version_ | 1811683679033884672 |
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| 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 |
| 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 |
| author_sort | van Velzen, Laura S. |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T04:16:34Z |
| format | Journal Article |
| id | ntu-10356/148925 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:16:34Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-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 |
| 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 |
| title | 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_short | 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 |
| topic | Science::Medicine Depression Neuroscience |
| url | https://hdl.handle.net/10356/148925 |
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