Regional brain morphology and current antidepressant use: findings from 32 international cohorts from the ENIGMA major depressive disorder working group
Por:
Serrarens, C, Toenders, YJ, Pozzi, E, Aleman, A, Alexander, N, Basgöze, Z, Belov, V, Berger, K, Brosch, K, Bülow, R, Busatto, GF, Capitao, LP, Connolly, CG, Couvy-Duchesne, B, Cullen, KR, Dannlowski, U, Davey, CG, De Zubicaray, GI, Dima, D, Dohm, K, Enneking, V, Erwin-Grabner, T, Evermann, U, Fu, CHY, Fuentes-Claramonte, P, Godlewska, BR, Gonul, AS, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Hahn, T, Hall, G, Harrison, B, Heindel, W, Hermesdorf, M, Ho, TC, Ichikawa, N, Itai, E, Jahanshad, N, Jamalabadi, H, Jamieson, AJ, Jansen, A, Kircher, T, Klimes-Dougan, B, Krämer, B, Krug, A, Lancaster, TM, Leehr, EJ, Li, M, Linden, DEJ, MacMaster, F, McMahon, KL, Medland, SE, Mehler, DMA, Meinert, S, Mwangi, B, Nenadic, I, Okada, G, Okamoto, Y, Opel, N, Pfarr, JK, Pomarol-Clotet, E, Portella, MJ, Redlich, R, Reneman, L, Repple, J, Ringwald, K, Rodriguez-Cano, E, Rosa, PGP, Sacchet, MD, Sämann, PG, Salvador, R, Schrantee, A, Shinzato, H, Sim, K, Simulionyte, E, Soares, JC, Stein, DJ, Stein, F, Straube, B, Strike, LT, Thomas-Odenthal, F, Thomopoulos, SI, Thompson, PM, Van Tol, MJ, Usemann, P, Uyar, A, van der Wee, N, van der Werff, S, Vives-Gilabert, Y, Völzke, H, Walter, M, Whittle, S, Wittfeld, K, Wroblewski, A, Wu, MJ, Yang, TT, Zunta-Soares, GB, Veltman, DJ, Schmaal, L, van Velzen, LS
Publicada:
1 dic 2025
Ahead of Print:
1 nov 2025
Resumen:
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.
Filiaciones:
Serrarens, C:
Maastricht Univ, Mental Hlth & Neurosci Res Inst, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Changes GGZ, Breda, Netherlands
Toenders, YJ:
Orygen, Parkville, Vic, Australia
Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia
Leiden Univ, Dev & Educ Psychol, Leiden, Netherlands
Erasmus Univ, Erasmus Sch Social & Behav Sci, Rotterdam, Netherlands
Pozzi, E:
Orygen, Parkville, Vic, Australia
Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia
Aleman, A:
Univ Groningen, Univ Med Ctr Groningen, Cognit Neurosci Ctr, Dept Biomed Sci Cells & Syst, Groningen, Netherlands
Alexander, N:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Basgöze, Z:
Univ Minnesota, Dept Psychiat & Behav Sci, Minneapolis, MN USA
Belov, V:
Univ Med Ctr Gottingen UMG, Lab Syst Neurosci & Imaging Psychiat SNIP Lab, Gottingen, Germany
Berger, K:
Univ Munster, Inst Epidemiol & Social Med, Munster, Germany
Brosch, K:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Feinstein Inst Med Res, Inst Behav Sci, Manhasset, NY USA
Bülow, R:
Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany
German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany
Busatto, GF:
Univ Sao Paulo, Lab Psychiat Neuroimaging LIM 21, Dept & Inst Psiquiatria, Hosp Clin HCFMUSP,Fac Med, Sao Paulo, Brazil
Capitao, LP:
Univ Minho, Psychol Res Ctr CIPsi, Sch Psychol, Psychol Neurosci Lab, Braga, Portugal
Connolly, CG:
Florida State Univ, Dept Biomed Sci, Tallahassee, FL USA
Couvy-Duchesne, B:
Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia
Sorbonne Univ, Hop Pitie Salpetriere, AP HP,Paris Brain Inst ICM, CNRS,Inst Cerveau,INRIA,INSERM, Paris, France
Cullen, KR:
Univ Minnesota, Dept Psychiat & Behav Sci, Minneapolis, MN USA
Dannlowski, U:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Bielefeld Univ, Med Sch, Bielefeld, Germany
Univ Med Ctr OWL, Protestant Hosp, Dept Psychiat, Bethel Fdn, Bielefeld, Germany
Davey, CG:
Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
De Zubicaray, GI:
Queensland Univ Technol, Fac Hlth, Sch Psychol & Counseling, Kelvin Grove, Qld, Australia
Dima, D:
City Univ London, Sch Hlth & Psychol Sci, Dept Psychol, London, England
Kings Coll London, Dept Neuroimaging, Inst Psychiat Psychol & Neurosci, London, England
Dohm, K:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Enneking, V:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Erwin-Grabner, T:
Univ Med Ctr Gottingen UMG, Lab Syst Neurosci & Imaging Psychiat SNIP Lab, Gottingen, Germany
Evermann, U:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Fu, CHY:
Univ East London, Sch Psychol, London, England
Kings Coll London, Ctr Affect Disorders, Inst Psychiat Psychol & Neurosci, London, England
Fuentes-Claramonte, P:
FIDMAG Germanes Hosp, Res Fdn, Barcelona, Spain
CIBERSAM ISCIII, Madrid, Spain
Godlewska, BR:
Univ Oxford, Dept Psychiat, Clin Psychopharmacol Grp, Oxford, England
Gonul, AS:
Ege Univ, Sch Med, Dept Psychiat, SoCAT Lab, Izmir, Turkiye
Mercer Univ, Sch Med, Dept Psychiat & Behav Sci, Macon, GA USA
Gotlib, IH:
Stanford Univ, Dept Psychol, Stanford, CA USA
Goya-Maldonado, R:
Univ Med Ctr Gottingen UMG, Lab Syst Neurosci & Imaging Psychiat SNIP Lab, Gottingen, Germany
Grabe, HJ:
Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany
Groenewold, NA:
Univ Cape Town, Neurosci Inst, Dept Psychiat & Mental Hlth, Cape Town, South Africa
Grotegerd, D:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Gruber, O:
Heidelberg Univ Hosp, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany
Hahn, T:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Hall, G:
McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada
Harrison, B:
Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
Heindel, W:
Univ Munster, Univ Clin Radiol, Munster, Germany
Hermesdorf, M:
Univ Munster, Inst Epidemiol & Social Med, Munster, Germany
Ho, TC:
Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA
Ichikawa, N:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Psychiat & Neurosci, Hiroshima, Japan
Itai, E:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Psychiat & Neurosci, Hiroshima, Japan
Jahanshad, N:
Univ Southern Calif, Mark & Mary Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Keck Sch Med, Los Angeles, CA USA
Jamalabadi, H:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Jamieson, AJ:
Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
Jansen, A:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Univ Marburg, Fac Med, Core Unit Brainimaging, Marburg, Germany
Kircher, T:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Klimes-Dougan, B:
Univ Minnesota, Dept Psychol, Minneapolis, MN USA
Krämer, B:
Heidelberg Univ Hosp, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany
Krug, A:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Hosp Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany
Lancaster, TM:
Cardiff Univ, Brain Res Imaging Ctr CUBRIC, Maindy Rd, Cardiff, Wales
Univ Bath, Dept Psychol, Bath, England
Leehr, EJ:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Li, M:
Jena Univ Hosp, Dept Psychiat & Psychotherapy, Jena, Germany
Ctr Intervent & Res adapt & maladapt brain Circuit, Halle Jena, Magdeburg, Germany
Otto von Guericke Univ, Clin Affect Neuroimaging Lab, Magdeburg, Germany
Linden, DEJ:
Maastricht Univ, Mental Hlth & Neurosci Res Inst, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Cardiff Univ, Brain Res Imaging Ctr CUBRIC, Maindy Rd, Cardiff, Wales
MacMaster, F:
IWK Hlth, Halifax, NS, Canada
Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada
Medland, SE:
QIMR Berghofer Med Res Inst, Herston, Australia
Mehler, DMA:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Cardiff Univ, Brain Res Imaging Ctr CUBRIC, Maindy Rd, Cardiff, Wales
Rhein Westfal TH Aachen, Med Sch, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany
Meinert, S:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Mwangi, B:
Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Louis A Faillace MD Dept Psychiat & Behav Sci, Ctr Excellence Mood Disorders, Houston, TX USA
Nenadic, I:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Okada, G:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Psychiat & Neurosci, Hiroshima, Japan
Okamoto, Y:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Psychiat & Neurosci, Hiroshima, Japan
Opel, N:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Jena Univ Hosp, Dept Psychiat & Psychotherapy, Jena, Germany
Ctr Intervent & Res adapt & maladapt brain Circuit, Halle Jena, Magdeburg, Germany
German Ctr Mental Hlth DZPG, Partner Site Halle Jena, Magdeburg, Germany
Pfarr, JK:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
McGill, Montreal Neurol Inst, Origami Lab, Montreal, PQ, Canada
Pomarol-Clotet, E:
FIDMAG Germanes Hosp, Res Fdn, Barcelona, Spain
CIBERSAM ISCIII, Madrid, Spain
Portella, MJ:
CIBERSAM ISCIII, Madrid, Spain
Inst Recerca St Pau IR St PAU, Mental Hlth Res Grp, Barcelona, Spain
Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Barcelona, Spain
Redlich, R:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Univ Halle, Dept Psychol, Halle, Germany
German Ctr Mental Hlth, Halle Site, Halle, Germany
Reneman, L:
Univ Amsterdam, Dept Radiol & Nucl Med, Locat AMC, Med Ctr, Amsterdam, Netherlands
Repple, J:
Univ Munster, Inst Translat Psychiat, Munster, Germany
Goethe Univ, Dept Psychiat Psychosomat Med & Psychotherapy, Univ Hosp Frankfurt, Frankfurt, Germany
Ringwald, K:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Rodriguez-Cano, E:
FIDMAG Germanes Hosp, Res Fdn, Barcelona, Spain
CIBERSAM ISCIII, Madrid, Spain
Rosa, PGP:
Univ Sao Paulo, Lab Psychiat Neuroimaging LIM 21, Dept & Inst Psiquiatria, Hosp Clin HCFMUSP,Fac Med, Sao Paulo, Brazil
Sacchet, MD:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Meditat Res Program, Boston, MA USA
Sämann, PG:
Max Planck Inst Psychiat, Munich, Germany
Salvador, R:
FIDMAG Germanes Hosp, Res Fdn, Barcelona, Spain
CIBERSAM ISCIII, Madrid, Spain
Schrantee, A:
Univ Amsterdam, Dept Radiol & Nucl Med, Locat AMC, Med Ctr, Amsterdam, Netherlands
Shinzato, H:
Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Psychiat & Neurosci, Hiroshima, Japan
Univ Ryukyus, Grad Sch Med, Dept Neuropsychiat, Okinawa, Japan
Sim, K:
Inst Mental Hlth, West Reg, Singapore, Singapore
Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore
Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore
Simulionyte, E:
Heidelberg Univ Hosp, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany
Soares, JC:
Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Louis A Faillace MD Dept Psychiat & Behav Sci, Ctr Excellence Mood Disorders, Houston, TX USA
Stein, DJ:
Univ Cape Town, Dept Psychiat, SAMRC Unit Risk & Resilience, Cape Town, South Africa
Univ Cape Town, Neurosci Inst, Cape Town, South Africa
Stein, F:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Straube, B:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Strike, LT:
QIMR Berghofer Med Res Inst, Herston, Australia
Thomas-Odenthal, F:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Thomopoulos, SI:
Univ Southern Calif, Mark & Mary Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Keck Sch Med, Los Angeles, CA USA
Thompson, PM:
Univ Southern Calif, Mark & Mary Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Keck Sch Med, Los Angeles, CA USA
Van Tol, MJ:
Univ Groningen, Univ Med Ctr Groningen, Cognit Neurosci Ctr, Groningen, Netherlands
Usemann, P:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Univ Marburg, Ctr Mind Brain & Behav, Marburg, Germany
Uyar, A:
Ege Univ, Sch Med, Dept Psychiat, SoCAT Lab, Izmir, Turkiye
Mugla Training & Res Hosp, Dept Psychiat, Mugla, Turkiye
van der Wee, N:
Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands
Leiden Inst Brain & Cognit, Leiden, Netherlands
van der Werff, S:
Leiden Univ, Dept Psychiat, Med Ctr, Leiden, Netherlands
Leiden Inst Brain & Cognit, Leiden, Netherlands
Vives-Gilabert, Y:
Univ Valencia, Dept Elect Engn, Intelligent Data Anal Lab, Valencia, Spain
Völzke, H:
German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany
Univ Med Greifswald, Inst Community Med, Greifswald, Germany
Walter, M:
Jena Univ Hosp, Dept Psychiat & Psychotherapy, Jena, Germany
Ctr Intervent & Res adapt & maladapt brain Circuit, Halle Jena, Magdeburg, Germany
German Ctr Mental Hlth DZPG, Partner Site Halle Jena, Magdeburg, Germany
Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany
Whittle, S:
Univ Melbourne, Dept Psychiat, Parkville, Vic, Australia
Wittfeld, K:
Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany
Wroblewski, A:
Philipps Univ Marburg, Fac Med, Dept Psychiat & Psychotherapy, Marburg, Germany
Wu, MJ:
Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Louis A Faillace MD Dept Psychiat & Behav Sci, Ctr Excellence Mood Disorders, Houston, TX USA
Yang, TT:
UCSF, Weill Inst Neurosci, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat,Sch Med, San Francisco, CA USA
Zunta-Soares, GB:
Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Louis A Faillace MD Dept Psychiat & Behav Sci, Ctr Excellence Mood Disorders, Houston, TX USA
Veltman, DJ:
Vrije Univ Amsterdam, Dept Psychiat, Amsterdam UMC Locat, Amsterdam, Netherlands
Amsterdam Neurosci, Brain Imaging program, Amsterdam, Netherlands
Schmaal, L:
Orygen, Parkville, Vic, Australia
Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia
van Velzen, LS:
Orygen, Parkville, Vic, Australia
Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia
Queensland Univ Technol, Sch Clin Sci, Brisbane, Qld, Australia
Green Submitted, Green Published, hybrid
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