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Record W4415827737 · doi:10.1038/s41380-025-03310-8

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

2025· article· en· W4415827737 on OpenAlexaff
Chaira Serrarens, Yara J. Toenders, Elena Pozzi, André Alemán, Nina Alexander, Zeynep Başgöze, V. Belov, Klaus Berger, Katharina Brosch, Robin Bülow, Geraldo F. Busatto, Liliana Capitão, Colm G. Connolly, Baptiste Couvy‐Duchesne, Kathryn R. Cullen, Udo Dannlowski, Christopher G. Davey, Greig I. de Zubicaray, Danai Dima, Katharina Dohm, Verena Enneking, Tracy Erwin-Grabner, Ulrika Evermann, Cynthia H.Y. Fu, Paola Fuentes‐Claramonte, Beata R. Godlewska, Ali Saffet Gönül, Ian H. Gotlib, Roberto Goya‐Maldonado, Hans J. Grabe, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Tim Hahn, Geoffrey B. Hall, Ben J. Harrison, Walter Heindel, Marco Hermesdorf, Tiffany C. Ho, Naho Ichikawa, Eri Itai, Neda Jahanshad, Hamidreza Jamalabadi, Alec J. Jamieson, Andreas Jansen, Tilo Kircher, Bonnie Klimes‐Dougan, Bernd Krämer, Axel Krug, T. Lancaster, Elisabeth J. Leehr, Meng Li, David E.J. Linden, Frank P. MacMaster, Katie L. McMahon, Sarah E. Medland, David M. A. Mehler, Susanne Meinert, Benson Mwangi, Igor Nenadić, Go Okada, Yasumasa Okamoto, Nils Opel, Julia‐Katharina Pfarr, Edith Pomarol-Clotet, Marı́a J. Portella, Ronny Redlich, Liesbeth Reneman, Jonathan Repple, Kai G. Ringwald, Elena Rodríguez‐Cano, Pedro G. P. Rosa, Matthew D. Sacchet, Philipp G. Sämann, Raymond Salvador, Anouk Schrantee, Hotaka Shinzato, Kang Sim, Egle Simulionyte, Jair C. Soares, Dan J. Stein, Frederike Stein, Benjamin Straube, Lachlan T. Strike, Florian Thomas‐Odenthal, Sophia I. Thomopoulos, Paul M. Thompson, Marie‐José van Tol, Paula Usemann, Aslihan Uyar-Demir, Nic J.A. van der Wee, Steven van der Werff, Yolanda Vives‐Gilabert, Henry Völzke, Martin Walter, Sarah Whittle, Katharina Wittfeld, Adrian Wroblewski, Mon‐Ju Wu, Tony T. Yang, Giovana Zunta‐Soares, Dick J. Veltman, Lianne Schmaal, Laura S. van Velzen

Bibliographic record

VenueMolecular Psychiatry · 2025
Typearticle
Languageen
FieldMedicine
TopicTreatment of Major Depression
Canadian institutionsCapital District Health AuthorityMontreal Neurological Institute and HospitalIzaak Walton Killam Health CentreDalhousie UniversityMcMaster University
FundersNational Center for Research ResourcesNational Institute of Child Health and Human DevelopmentNational Institute of Biomedical Imaging and BioengineeringNational Institute of Mental HealthAgència de Gestió d'Ajuts Universitaris i de RecercaNational Health and Medical Research CouncilU.S. Department of Health and Human ServicesGratama StichtingUniversity of OxfordGeneralitat de CatalunyaNational Healthcare GroupBundesministerium für Bildung und ForschungNational Center for Complementary and Integrative HealthNational Institute for Health and Care ResearchUniversidade do MinhoInstituto de Salud Carlos IIIHessisches Ministerium für Wissenschaft und KunstLivaNovaUniversity of Texas Health Science Center at HoustonUniversitätsmedizin GöttingenEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentFundação para a Ciência e a TecnologiaCentro de Investigación Biomédica en Red de Salud MentalNational Alliance for Research on Schizophrenia and DepressionDeutsche ForschungsgemeinschaftJapan Agency for Medical Research and DevelopmentNational Center for Advancing Translational SciencesMedical Research CouncilAmerican Foundation for Suicide PreventionJohn S. Dunn FoundationCentres de Recerca de CatalunyaSunovionUniversity of MinnesotaNational Institutes of Health
KeywordsMajor depressive disorderBrain morphometryNeuroimagingParahippocampal gyrusAntidepressantBrain sizeCohortLingual gyrusHippocampal formationMirtazapine

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.276
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations1
Published2025
Admission routes1
Has abstractyes

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