Regional brain morphology and current antidepressant use: findings from 32 international cohorts from the ENIGMA major depressive disorder working group

Serrarens, Chaira, Toenders, Yara J., Pozzi, Elena, Aleman, André, Alexander, Nina, Başgöze, Zeynep, Belov, Vladimir, Berger, Klaus, Brosch, Katharina, Bülow, Robin, Busatto, Geraldo Filho, Capitão, Liliana P., Connolly, Colm G., Couvy-Duchesne, Baptiste, Cullen, Kathryn R., Dannlowski, Udo, Davey, Christopher G., de Zubicaray, Greig I., Dima, Danai, Dohm, Katharina, Enneking, Verena, Erwin-Grabner, Tracy, Evermann, Ulrika, Fu, Cynthia H. Y., Fuentes-Claramonte, Paola, Godlewska, Beata R., Gonul, Ali Saffet, Gotlib, Ian H., Goya-Maldonado, Roberto, Grabe, Hans J., Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Hahn, Tim, Hall, Geoffrey, Harrison, Ben J., Heindel, Walter, Hermesdorf, Marco, Ho, Tiffany C., Ichikawa, Naho, Itai, Eri, Jahanshad, Neda, Jamalabadi, Hamidreza, Jamieson, Alec J., Jansen, Andreas, Kircher, Tilo, Klimes-Dougan, Bonnie, Krämer, Bernd, Krug, Axel, Lancaster, Thomas M. ORCID: https://orcid.org/0000-0003-1322-2449, Leehr, Elisabeth J., Li, Meng, Linden, David E. J. ORCID: https://orcid.org/0000-0002-5638-9292, MacMaster, Frank, McMahon, Katie L., Medland, Sarah E., Mehler, David M. A., Meinert, Susanne, Mwangi, Benson, Nenadić, Igor, Okada, Go, Okamoto, Yasumasa, Opel, Nils, Pfarr, Julia-Katharina, Pomarol-Clotet, Edith, Portella, Maria J., Redlich, Ronny, Reneman, Liesbeth, Repple, Jonathan, Ringwald, Kai, Rodriguez-Cano, Elena, Rosa, Pedro G. P., Sacchet, Matthew D., Sämann, Philipp G., Salvador, Raymond, Schrantee, Anouk, Shinzato, Hotaka, Sim, Kang, Simulionyte, Egle, Soares, Jair C., Stein, Dan J., Stein, Frederike, Straube, Benjamin, Strike, Lachlan T., Thomas-Odenthal, Florian, Thomopoulos, Sophia I., Thompson, Paul M., van Tol, Marie-Jose, Usemann, Paula, Uyar, Aslihan, van der Wee, Nic, van der Werff, Steven, Vives-Gilabert, Yolanda, Völzke, Henry, Walter, Martin, Whittle, Sarah, Wittfeld, Katharina, Wroblewski, Adrian, Wu, Mon-Ju, Yang, Tony T., Zunta-Soares, Giovana B., Veltman, Dick J., Schmaal, Lianne and van Velzen, Laura S. 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. 10.1038/s41380-025-03310-8

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Psychology Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	1359-4184
Date of First Compliant Deposit:	17 November 2025
Date of Acceptance:	15 October 2025
Last Modified:	17 Nov 2025 17:01
URI:	https://orca.cardiff.ac.uk/id/eprint/182468

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