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Serrarens, C., Toenders, Y. J. ORCID: 0000-0002-4117-1143, Pozzi, E. , Aleman, A., Alexander, N., Başgöze, Z. ORCID: 0000-0002-0306-4849, Belov, V., Berger, K., Brosch, K. ORCID: 0000-0002-0526-8095, Bülow, R. ORCID: 0000-0003-1884-5784, Busatto, G. F. ORCID: 0000-0003-4749-4602, Capitão, L. P. ORCID: 0000-0003-3117-5156, Connolly, C. G., Couvy-Duchesne, B. ORCID: 0000-0002-0719-9302, Cullen, K. R. ORCID: 0000-0001-9631-3770, Dannlowski, U., Davey, C. G. ORCID: 0000-0003-1431-3852, de Zubicaray, G. I. ORCID: 0000-0003-4506-0579, Dima, D. ORCID: 0000-0002-2598-0952, Dohm, K., Enneking, V., Erwin-Grabner, T., Evermann, U. ORCID: 0000-0002-3250-7821, Fu, C. H. Y. ORCID: 0000-0003-4313-3500, Fuentes-Claramonte, P. ORCID: 0000-0002-1428-7976, Godlewska, B. R. ORCID: 0000-0002-5973-3765, Gonul, A. S., Gotlib, I. H. ORCID: 0000-0002-3622-3199, Goya-Maldonado, R. ORCID: 0000-0002-7368-1332, Grabe, H. J., Groenewold, N. A. ORCID: 0000-0002-0865-8427, Grotegerd, D. ORCID: 0000-0001-8718-0128, Gruber, O., Hahn, T. ORCID: 0000-0001-6541-3795, Hall, G., Harrison, B. J., Heindel, W., Hermesdorf, M., Ho, T. C., Ichikawa, N., Itai, E., Jahanshad, N., Jamalabadi, H. ORCID: 0000-0003-2485-2374, Jamieson, A. J. ORCID: 0000-0002-5598-0240, Jansen, A., Kircher, T. ORCID: 0000-0002-2514-2625, Klimes-Dougan, B. ORCID: 0000-0002-2107-0038, Krämer, B. ORCID: 0000-0002-1145-9103, Krug, A. ORCID: 0000-0002-0564-2497, Lancaster, T. M., Leehr, E. J. ORCID: 0000-0002-9264-5003, Li, M. ORCID: 0000-0002-8320-5241, Linden, D. E. J., MacMaster, F., McMahon, K. L. ORCID: 0000-0002-6357-615X, Medland, S. E. ORCID: 0000-0003-1382-380X, Mehler, D. M. A. ORCID: 0000-0001-6587-2617, Meinert, S. ORCID: 0000-0003-2177-7161, Mwangi, B., Nenadić, I., Okada, G., Okamoto, Y., Opel, N. ORCID: 0000-0003-4749-3298, Pfarr, J-K., Pomarol-Clotet, E., Portella, M. J. ORCID: 0000-0002-2007-9516, Redlich, R., Reneman, L., Repple, J., Ringwald, K., Rodriguez-Cano, E. ORCID: 0000-0002-5011-567X, Rosa, P. G. P., Sacchet, M. D., Sämann, P. G. ORCID: 0000-0001-8523-3628, Salvador, R., Schrantee, A. ORCID: 0000-0002-4035-4845, Shinzato, H. ORCID: 0000-0002-0354-1801, Sim, K., Simulionyte, E., Soares, J. C. ORCID: 0000-0002-5466-5628, Stein, D. J. ORCID: 0000-0001-7218-7810, Stein, F. ORCID: 0000-0002-5052-6022, Straube, B. ORCID: 0000-0002-9837-0944, Strike, L. T., Thomas-Odenthal, F., Thomopoulos, S. I. ORCID: 0000-0002-0046-4070, Thompson, P. M., van Tol, M-J. ORCID: 0000-0002-9260-5490, Usemann, P., Uyar, A. ORCID: 0000-0002-0856-4260, van der Wee, N., van der Werff, S., Vives-Gilabert, Y., Völzke, H., Walter, M. ORCID: 0000-0001-7857-4483, Whittle, S. ORCID: 0000-0003-3145-1528, Wittfeld, K. ORCID: 0000-0003-4383-5043, Wroblewski, A. ORCID: 0000-0002-0371-7686, Wu, M-J. ORCID: 0000-0002-0540-8027, Yang, T. T., Zunta-Soares, G. B., Veltman, D. J., Schmaal, L. ORCID: 0000-0001-9822-048X & van Velzen, L. S. ORCID: 0000-0002-6003-5227view all authors (2025). Regional brain morphology and current antidepressant use: findings from 32 international cohorts from the ENIGMA major depressive disorder working group. Molecular Psychiatry, 30(12), pp. 5625-5636. doi: 10.1038/s41380-025-03310-8

Abstract

The understanding of how antidepressant (AD) use is associated with brain structure in individuals with major depressive disorder (MDD) remains incomplete. We aimed to examine the association between AD medication use and brain morphology in relation to age and sex by pooling structural neuroimaging and clinical data from 32 cohorts within the ENIGMA-MDD working group. Interaction effects of group (2076 cases with current AD use (AD), 1495 cases not currently taking AD (nAD) and 5125 healthy controls (HC)) with age and sex, and main effects of group on regional brain structure (cortical surface area and thickness, and subcortical volume) were examined. Additionally, we examined the effect of AD type (SSRI, SNRI or mirtazapine) and duration of use on brain morphology. Younger individuals in the AD group showed lower bilateral middle temporal gyrus thickness compared to nAD and HC, but this was not seen in older individuals (crossover around 50 years). Lower hippocampal volume and thinner inferior temporal gyrus were shown in AD compared to nAD. These effects were independent of group differences in disease-course-related measures, but were driven by depressive symptom severity. Greater bilateral rostral anterior cingulate thickness was found in individuals older than approximately 40 years taking mirtazapine compared to individuals taking SSRIs or SNRIs. Evidence for subtle structural brain differences in temporal and limbic regions in individuals with MDD who currently use AD medication were found compared to those not currently taking AD medication. Future longitudinal studies are needed to determine the causality of these associations.

Publication Type:	Article
Additional Information:	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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2025
Subjects:	B Philosophy. Psychology. Religion > BF Psychology 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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Official URL: https://doi.org/10.1038/s41380-025-03310-8

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