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

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.

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Publication Details

Journal
Molecular Psychiatry
Published
2025-11-03
DOI
https://doi.org/10.1038/s41380-025-03310-8
Citations
1
Primary Topic
Treatment of Major Depression
Type
article
Field-Weighted Citation Impact
1.39

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article

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

Ronny Redlich, V. Belov, Beata R. Godlewska, Roberto Goya‐Maldonado et al.
1 citations
Molecular Psychiatry
Treatment of Major Depression
1.39
article

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

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

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.

Molecular PsychiatryVol. 30(12)
Florida State University (US), Hiroshima University (JP), Goethe University Frankfurt (DE), University of Southern California (US), Leiden University (NL), Universitat Autònoma de Barcelona (ES), Montreal Neurological Institute and Hospital (CA), Centre National de la Recherche Scientifique (FR), Netherlands Institute for Neuroscience (NL), Dalhousie University (CA), University of Minnesota (US), Capital District Health Authority (CA), Feinstein Institute for Medical Research (US), University Medical Center Groningen (NL), Harvard University (US), Mercer University (US), Inserm (FR), University of East London (GB), University of Cape Town (ZA), Universitat de València (ES), Queensland University of Technology (AU), Philipps University of Marburg (DE), University of California, Los Angeles (US), The University of Queensland (AU), The University of Melbourne (AU), National University of Singapore (SG), Nanyang Technological University (SG), City, University of London (GB), King's College London (GB), American Academy of Child and Adolescent Psychiatry (US), QIMR Berghofer Medical Research Institute (AU), Heidelberg University (DE), University of Münster (DE), Universitätsmedizin Greifswald (DE), University Hospital Bonn (DE), Leiden University Medical Center (NL), Izaak Walton Killam Health Centre (CA), Instituto de Salud Carlos III (ES), Hospital de Sant Pau (ES), Oxford Research Group (GB), University Hospital Heidelberg (DE), University of the Ryukyus (JP), Maastricht University (NL), Sorbonne Université (FR), Ege University (TR), Massachusetts General Hospital (US), Centro de Investigación Biomédica en Red de Salud Mental (ES), Orygen Youth Health (AU), Assistance Publique – Hôpitaux de Paris (FR), University Hospital Münster (DE), Mental Health Australia (AU), Amsterdam Neuroscience (NL), Orygen (AU), Brain (Germany) (DE), Institut de Myologie (FR), Universitätsmedizin Göttingen (DE), GGz Breburg (NL), Fidmag Sisters Hospitallers (ES), Center for Behavioral Brain Sciences (DE), German Centre for Cardiovascular Research (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Institute of Mental Health (SG), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Max Planck Institute of Psychiatry (DE), Amsterdam University Medical Centers (NL), University Hospital in Halle (DE), Institut du Cerveau (FR), The University of Texas Health Science Center (US), University of Bath (GB), University of Göttingen (DE), Cardiff University (GB), Muğla University (TR), University of Tübingen (DE), Vrije Universiteit Amsterdam (NL), RWTH Aachen University (DE), Bethel University (US), Erasmus University Rotterdam (NL), Otto-von-Guericke-Universität Magdeburg (DE), Stanford University (US), McMaster University (CA), University of Minho (PT)
American Foundation for Suicide Prevention, John S. Dunn Foundation, University of Minnesota, Japan Agency for Medical Research and Development, Sunovion, National Alliance for Research on Schizophrenia and Depression, University of Texas Health Science Center at Houston, LivaNova, Centres de Recerca de Catalunya, Universitätsmedizin Göttingen, National Institute for Health and Care Research, University of Oxford, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Hessisches Ministerium für Wissenschaft und Kunst, Centro de Investigación Biomédica en Red de Salud Mental, Gratama Stichting, Universidade do Minho, National Healthcare Group, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Fundação para a Ciência e a Tecnologia, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, National Institute of Mental Health, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences
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Treatment of Major Depression
1.39
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