Vertex-wise cortical abnormalities in major depressive disorder from 64 cohorts from the DIRECT and ENIGMA MDD consortia

Yan, C-G.; Wang, Z-H.; Han, L. K. M.; Alexander, N.; Alnæs, D.; Başgöze, Z.; Bauduin, S. E. E. C.; Bauer, J.; Benedetti, F.; Berger, K.; Besteher, B.; Borgers, T.; Bülow, R.; Cao, L-P.; Chen, G-M.; Chen, J-S.; Chen, S-C.; Chen, T.; Chen, T-L.; Chen, X.; Chen, Y-R.; Cheng, Y-Q.; Chu, Z-S.; Colle, R.; Connolly, C. G.; Corruble, E.; Couvy-Duchesne, B.; Cui, X-L.; Cullen, K. R.; Dannlowski, U.; Davey, C.; Dima, D.; Dols, A.; Erwin-Grabner, T.; Evans, J. W.; Flinkenflügel, K.; Fu, C. H. Y.; Fuentes-Claramonte, P.; Gao, Q-L.; Gong, Q-Y.; Gönül, A. S.; Gotlib, I. H.; Goya-Maldonado, R.; Grabe, H. J.; Groenewold, N.; Grotegerd, D.; Guo, W-B.; Hahn, T.; Hall, G. B.; Hamilton, J. P.; Harrison, B.; Hatton, S.; He, C-C.; Hermesdorf, M.; Hickie, I. B.; Ho, T. C.; Hu, Z-J-Y.; Huang, Q.; Jahanshad, N.; Jamalabadi, H.; Jamieson, A.; Ji, X-L.; Jia, F-N.; Kamishikiryo, T.; Kircher, T.; Koopowitz, S-M.; Kraus, A.; Krug, A.; Kuang, L.; Lagopoulos, J.; Lancaster, T.; Landrø, N. I.; Leehr, E. J.; Li, M.; Li, B-J.; Li, F.; Li, H-X.; Li, T.; Li, X-Y.; Liao, Y-F.; Lin, Z-D.; Linden, D. E. J.; Liu, H-L.; Liu, X-Y.; Liu, Z-N.; Liu, Y-S.; Long, Y-C.; Lu, J-P.; Lu, B.; MacMaster, F. P.; Maglanoc, L. A.; McIntosh, A. M.; Medland, S.; Mehler, D. M. A.; Meinert, S.; Mwangi, B.; Ojha, A.; Okada, G.; Oudega, M. L.; Penninx, B. W. J. H.; Poletti, S.; Pomarol-Clotet, E.; Portella, M. J.; Qiu, J.; Reneman, L.; Rise, H. S.; Rodriguez-Cano, E.; Sacchet, M. D.; Salvador, R.; Schlieper, H.; Schrantee, A.; Shan, X-X.; Shinzato, H.; Si, T-M.; Sim, K.; Soares, J. C.; Stein, D. J.; Straube, B.; Strike, L. T.; Sun, P-F.; Thomas-Odenthal, F.; Thomopoulos, S. I.; Thompson, P. M.; Toenders, Y.; Uyar, A.; van der Wee, N. J. A.; van der Werff, S. J. A.; Veer, I. M.; Veltman, D. J.; Völzke, H.; Wagenmakers, M.; Walter, H.; Walter, M.; Wang, C-Y.; Wang, H-L.; Wang, H-N.; Wang, X.; Wang, X-Y.; Wang, Y.; Wang, Y-W.; Westlye, L. T.; Whalley, H. C.; Whittle, S.; Winter, N. R.; Wittfeld, K.; Wu, M-J.; Wu, X-P.; Wu, X-R.; Wu, Y-K.; Wu, C-N.; Xie, C-M.; Xie, G-R.; Xie, P.; Xu, X-F.; Xue, Z-P.; Yang, T. T.; Yang, H.; Yang, J.; Yu, H.; Yu, Y-Q.; Yuan, M-L.; Yuan, Y-G.; Zang, Y-F.; Zarate, C. A.; Zhang, A-X.; Zhang, K-R.; Zhang, W.; Zhao, J-P.; Zhong, W-Y.; Zhu, J-J.; Zunta-Soares, G. B.; Zuo, X-N.; Pozzi, E.; Schmaal, L.

Vertex-wise cortical abnormalities in major depressive disorder from 64 cohorts from the DIRECT and ENIGMA MDD consortia

Yan, C-G., Wang, Z-H., Han, L. K. M. , Alexander, N., Alnæs, D., Başgöze, Z., Bauduin, S. E. E. C., Bauer, J., Benedetti, F., Berger, K., Besteher, B., Borgers, T., Bülow, R., Cao, L-P., Chen, G-M., Chen, J-S., Chen, S-C., Chen, T., Chen, T-L., Chen, X., Chen, Y-R., Cheng, Y-Q., Chu, Z-S., Colle, R., Connolly, C. G., Corruble, E., Couvy-Duchesne, B., Cui, X-L., Cullen, K. R., Dannlowski, U., Davey, C., Dima, D. ORCID: 0000-0002-2598-0952, Dols, A., Erwin-Grabner, T., Evans, J. W., Flinkenflügel, K., Fu, C. H. Y., Fuentes-Claramonte, P., Gao, Q-L., Gong, Q-Y., Gönül, A. S., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Groenewold, N., Grotegerd, D., Guo, W-B., Hahn, T., Hall, G. B., Hamilton, J. P., Harrison, B., Hatton, S., He, C-C., Hermesdorf, M., Hickie, I. B., Ho, T. C., Hu, Z-J-Y., Huang, Q., Jahanshad, N., Jamalabadi, H., Jamieson, A., Ji, X-L., Jia, F-N., Kamishikiryo, T., Kircher, T., Koopowitz, S-M., Kraus, A., Krug, A., Kuang, L., Lagopoulos, J., Lancaster, T., Landrø, N. I., Leehr, E. J., Li, M., Li, B-J., Li, F., Li, H-X., Li, T., Li, X-Y., Liao, Y-F., Lin, Z-D., Linden, D. E. J., Liu, H-L., Liu, X-Y., Liu, Z-N., Liu, Y-S., Long, Y-C., Lu, J-P., Lu, B., MacMaster, F. P., Maglanoc, L. A., McIntosh, A. M., Medland, S., Mehler, D. M. A., Meinert, S., Mwangi, B., Ojha, A., Okada, G., Oudega, M. L., Penninx, B. W. J. H., Poletti, S., Pomarol-Clotet, E., Portella, M. J., Qiu, J., Reneman, L., Rise, H. S., Rodriguez-Cano, E., Sacchet, M. D., Salvador, R., Schlieper, H., Schrantee, A., Shan, X-X., Shinzato, H., Si, T-M., Sim, K., Soares, J. C., Stein, D. J., Straube, B., Strike, L. T., Sun, P-F., Thomas-Odenthal, F., Thomopoulos, S. I., Thompson, P. M., Toenders, Y., Uyar, A., van der Wee, N. J. A., van der Werff, S. J. A., Veer, I. M., Veltman, D. J., Völzke, H., Wagenmakers, M., Walter, H., Walter, M., Wang, C-Y., Wang, H-L., Wang, H-N., Wang, X., Wang, X-Y., Wang, Y., Wang, Y-W., Westlye, L. T., Whalley, H. C., Whittle, S., Winter, N. R., Wittfeld, K., Wu, M-J., Wu, X-P., Wu, X-R., Wu, Y-K., Wu, C-N., Xie, C-M., Xie, G-R., Xie, P., Xu, X-F., Xue, Z-P., Yang, T. T., Yang, H., Yang, J., Yu, H., Yu, Y-Q., Yuan, M-L., Yuan, Y-G., Zang, Y-F., Zarate, C. A., Zhang, A-X., Zhang, K-R., Zhang, W., Zhao, J-P., Zhong, W-Y., Zhu, J-J., Zunta-Soares, G. B., Zuo, X-N., Pozzi, E. & Schmaal, L. (2026). Vertex-wise cortical abnormalities in major depressive disorder from 64 cohorts from the DIRECT and ENIGMA MDD consortia. Nature Mental Health, doi: 10.1038/s44220-026-00667-9

Abstract

Major depressive disorder (MDD) is common and disabling, yet reported brain structural differences vary across studies. Here we performed a large vertex-wise (point-by-point) meta-analysis of cortical thickness and surface area using harmonized magnetic resonance imaging processing across 64 cohorts from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) MDD and Depression Imaging Research Consortium (DIRECT) consortia (5,736 patients; 6,538 controls). We show significantly lower cortical thickness in patients with MDD in multiple brain regions, including the inferior parietal, lateral occipital, superior parietal, medial and lateral orbitofrontal, anterior and posterior cingulate, and precentral gyri, with cortical surface area showing no significant differences. Effects were most pronounced in adults with acute depression, whereas adolescents showed no significant case–control differences. Antidepressant medication use at scanning was associated with more extensive thinning, although effect sizes remained modest (mostly |Cohen’s d| < 0.20). This high-resolution, globally generalizable map can support studies of mechanisms and help evaluate structural markers of the clinical course and treatment response.

Publication Type:	Article
Additional Information:	This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s44220-026-00667-9 Copyright - Springer Nature
Publisher Keywords:	Cognitive neuroscience, psychology, depression
Subjects:	B Philosophy. Psychology. Religion > BF Psychology Q Science > QM Human anatomy R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments:	School of Health & Medical Sciences School of Health & Medical Sciences > Department of Psychology & Neuroscience
SWORD Depositor:	Symplectic Administrator

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This document is not freely accessible until 15 December 2026 due to copyright restrictions.

Official URL: https://doi.org/10.1038/s44220-026-00667-9

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Creators:	Yan, C-G. Wang, Z-H. Han, L. K. M. Alexander, N. Alnæs, D. Başgöze, Z. Bauduin, S. E. E. C. Bauer, J. Benedetti, F. Berger, K. Besteher, B. Borgers, T. Bülow, R. Cao, L-P. Chen, G-M. Chen, J-S. Chen, S-C. Chen, T. Chen, T-L. Chen, X. Chen, Y-R. Cheng, Y-Q. Chu, Z-S. Colle, R. Connolly, C. G. Corruble, E. Couvy-Duchesne, B. Cui, X-L. Cullen, K. R. Dannlowski, U. Davey, C. Dima, D. ORCID: 0000-0002-2598-0952 Dols, A. Erwin-Grabner, T. Evans, J. W. Flinkenflügel, K. Fu, C. H. Y. Fuentes-Claramonte, P. Gao, Q-L. Gong, Q-Y. Gönül, A. S. Gotlib, I. H. Goya-Maldonado, R. Grabe, H. J. Groenewold, N. Grotegerd, D. Guo, W-B. Hahn, T. Hall, G. B. Hamilton, J. P. Harrison, B. Hatton, S. He, C-C. Hermesdorf, M. Hickie, I. B. Ho, T. C. Hu, Z-J-Y. Huang, Q. Jahanshad, N. Jamalabadi, H. Jamieson, A. Ji, X-L. Jia, F-N. Kamishikiryo, T. Kircher, T. Koopowitz, S-M. Kraus, A. Krug, A. Kuang, L. Lagopoulos, J. Lancaster, T. Landrø, N. I. Leehr, E. J. Li, M. Li, B-J. Li, F. Li, H-X. Li, T. Li, X-Y. Liao, Y-F. Lin, Z-D. Linden, D. E. J. Liu, H-L. Liu, X-Y. Liu, Z-N. Liu, Y-S. Long, Y-C. Lu, J-P. Lu, B. MacMaster, F. P. Maglanoc, L. A. McIntosh, A. M. Medland, S. Mehler, D. M. A. Meinert, S. Mwangi, B. Ojha, A. Okada, G. Oudega, M. L. Penninx, B. W. J. H. Poletti, S. Pomarol-Clotet, E. Portella, M. J. Qiu, J. Reneman, L. Rise, H. S. Rodriguez-Cano, E. Sacchet, M. D. Salvador, R. Schlieper, H. Schrantee, A. Shan, X-X. Shinzato, H. Si, T-M. Sim, K. Soares, J. C. Stein, D. J. Straube, B. Strike, L. T. Sun, P-F. Thomas-Odenthal, F. Thomopoulos, S. I. Thompson, P. M. Toenders, Y. Uyar, A. van der Wee, N. J. A. van der Werff, S. J. A. Veer, I. M. Veltman, D. J. Völzke, H. Wagenmakers, M. Walter, H. Walter, M. Wang, C-Y. Wang, H-L. Wang, H-N. Wang, X. Wang, X-Y. Wang, Y. Wang, Y-W. Westlye, L. T. Whalley, H. C. Whittle, S. Winter, N. R. Wittfeld, K. Wu, M-J. Wu, X-P. Wu, X-R. Wu, Y-K. Wu, C-N. Xie, C-M. Xie, G-R. Xie, P. Xu, X-F. Xue, Z-P. Yang, T. T. Yang, H. Yang, J. Yu, H. Yu, Y-Q. Yuan, M-L. Yuan, Y-G. Zang, Y-F. Zarate, C. A. Zhang, A-X. Zhang, K-R. Zhang, W. Zhao, J-P. Zhong, W-Y. Zhu, J-J. Zunta-Soares, G. B. Zuo, X-N. Pozzi, E. Schmaal, L.
Status:	Published
Refereed:	Yes
Journal or Publication Title:	Nature Mental Health
Publisher:	Springer Science and Business Media LLC
e-ISSN:	2731-6076
URI:	https://openaccess.city.ac.uk/id/eprint/37778
Date available in CRO:	19 Jun 2026 14:39
Date deposited:	19 June 2026
Dates:	Date Event 15 June 2026 Published Online 8 May 2026 Accepted

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