White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group. 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., Groenewold, N., A., Grotegerd, D., Harris, M., A., Hatton, S., N., Hawkins, E., L., Hickie, I., B., Ho, T., C., Jansen, A., Kircher, T., Klimes-Dougan, B., Kochunov, P., Krug, A., Lagopoulos, J., Lee, R., Lett, T., A., Li, M., MacMaster, F., P., Martin, N., G., McIntosh, A., M., McLellan, Q., Meinert, S., Nenadić, I., Osipov, E., Penninx, B., W., Portella, M., J., Repple, J., Roos, A., Sacchet, M., D., Sämann, P., G., Schnell, K., Shen, X., Sim, K., Stein, D., J., van Tol, M., J., Tomyshev, A., S., Tozzi, L., Veer, I., M., Vermeiren, R., Vives-Gilabert, Y., Walter, H., Walter, M., van der Wee, N., J., van der Werff, S., J., Schreiner, M., W., Whalley, H., C., Wright, M., J., Yang, T., T., Zhu, A., Veltman, D., J., Thompson, P., M., Jahanshad, N., & Schmaal, L. Molecular Psychiatry, 25(7):1511-1525, 2020.
abstract   bibtex   
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.
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 title = {White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group},
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 year = {2020},
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 abstract = {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.},
 bibtype = {article},
 author = {van Velzen, Laura S. and Kelly, Sinead and Isaev, Dmitry and Aleman, Andre and Aftanas, Lyubomir I. and Bauer, Jochen and Baune, Bernhard T. and Brak, Ivan V. and Carballedo, Angela and Connolly, Colm G. and Couvy-Duchesne, Baptiste and Cullen, Kathryn R. and Danilenko, Konstantin V. and Dannlowski, Udo and Enneking, Verena and Filimonova, Elena and Förster, Katharina and Frodl, Thomas and Gotlib, Ian H. and Groenewold, Nynke A. and Grotegerd, Dominik and Harris, Mathew A. and Hatton, Sean N. and Hawkins, Emma L. and Hickie, Ian B. and Ho, Tiffany C. and Jansen, Andreas and Kircher, Tilo and Klimes-Dougan, Bonnie and Kochunov, Peter and Krug, Axel and Lagopoulos, Jim and Lee, Renick and Lett, Tristram A. and Li, Meng and MacMaster, Frank P. and Martin, Nicholas G. and McIntosh, Andrew M. and McLellan, Quinn and Meinert, Susanne and Nenadić, Igor and Osipov, Evgeny and Penninx, Brenda W.J.H. and Portella, Maria J. and Repple, Jonathan and Roos, Annerine and Sacchet, Matthew D. and Sämann, Philipp G. and Schnell, Knut and Shen, Xueyi and Sim, Kang and Stein, Dan J. and van Tol, Marie Jose and Tomyshev, Alexander S. and Tozzi, Leonardo and Veer, Ilya M. and Vermeiren, Robert and Vives-Gilabert, Yolanda and Walter, Henrik and Walter, Martin and van der Wee, Nic J.A. and van der Werff, Steven J.A. and Schreiner, Melinda Westlund and Whalley, Heather C. and Wright, Margaret J. and Yang, Tony T. and Zhu, Alyssa and Veltman, Dick J. and Thompson, Paul M. and Jahanshad, Neda and Schmaal, Lianne},
 journal = {Molecular Psychiatry},
 number = {7}
}

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