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

Chaira Serrarens^{1

2}, Yara J Toenders^{3

4

5

6}, Elena Pozzi^{3

4}, André Aleman⁷, Nina Alexander^{8

9}, Zeynep Başgöze¹⁰, Vladimir Belov¹¹, Klaus Berger¹², Katharina Brosch^{8

9

13}, Robin Bülow^{14

15}, Geraldo Filho Busatto¹⁶, Liliana P Capitão¹⁷, Colm G Connolly¹⁸, Baptiste Couvy-Duchesne^{19

20}, Kathryn R Cullen¹⁰, Udo Dannlowski^{21

22}, Christopher G Davey²³, Greig I de Zubicaray²⁴, Danai Dima^{25

26}, Katharina Dohm²¹, Verena Enneking²¹, Tracy Erwin-Grabner¹¹, Ulrika Evermann⁸, Cynthia H Y Fu^{27

28}, Paola Fuentes-Claramonte^{29

30}, Beata R Godlewska³¹, Ali Saffet Gonul^{32

33}, Ian H Gotlib³⁴, Roberto Goya-Maldonado¹¹, Hans J Grabe³⁵, Nynke A Groenewold³⁶, Dominik Grotegerd²¹, Oliver Gruber³⁷, Tim Hahn²¹, Geoffrey Hall³⁸, Ben J Harrison²³, Walter Heindel³⁹, Marco Hermesdorf¹², Tiffany C Ho⁴⁰, Naho Ichikawa⁴¹, Eri Itai⁴¹, Neda Jahanshad⁴², Hamidreza Jamalabadi^{8

9}, Alec J Jamieson²³, Andreas Jansen^{8

9

43}, Tilo Kircher^{8

9}, Bonnie Klimes-Dougan⁴⁴, Bernd Krämer³⁷, Axel Krug^{8

45}, Thomas M Lancaster^{46

47}, Elisabeth J Leehr²¹, Meng Li^{48

49

50}, David E J Linden^{1

46}, Frank MacMaster^{51

52}, Katie L McMahon⁵³, Sarah E Medland⁵⁴, David M A Mehler^{21

46

55}, Susanne Meinert²¹, Benson Mwangi⁵⁶, Igor Nenadić^{8

9}, Go Okada⁴¹, Yasumasa Okamoto⁴¹, Nils Opel^{21

48

49

57}, Julia-Katharina Pfarr^{8

9

58}, Edith Pomarol-Clotet^{29

30}, Maria J Portella^{30

59

60}, Ronny Redlich^{21

61

62}, Liesbeth Reneman⁶³, Jonathan Repple^{21

64}, Kai Ringwald⁸, Elena Rodriguez-Cano^{29

30}, Pedro G P Rosa¹⁶, Matthew D Sacchet⁶⁵, Philipp G Sämann⁶⁶, Raymond Salvador^{29

30}, Anouk Schrantee⁶³, Hotaka Shinzato^{41

67}, Kang Sim^{68

69

70}, Egle Simulionyte³⁷, Jair C Soares⁵⁶, Dan J Stein⁷¹, Frederike Stein^{8

9}, Benjamin Straube^{8

9}, Lachlan T Strike⁵⁴, Florian Thomas-Odenthal^{8

9}, Sophia I Thomopoulos⁴², Paul M Thompson⁴², Marie-Jose van Tol⁷², Paula Usemann^{8

9}, Aslihan Uyar^{32

73}, Nic van der Wee^{74

75}, Steven van der Werff^{74

75}, Yolanda Vives-Gilabert⁷⁶, Henry Völzke^{15

77}, Martin Walter^{48

49

57

78}, Sarah Whittle²³, Katharina Wittfeld³⁵, Adrian Wroblewski⁸, Mon-Ju Wu⁵⁶, Tony T Yang⁷⁹, Giovana B Zunta-Soares⁵⁶, Dick J Veltman^{80

81}, Lianne Schmaal^#^{82

83}, Laura S van Velzen^#^{3

4}

Affiliations

¹ Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
² Changes GGZ, Breda, the Netherlands.
³ Orygen, Parkville, VIC, Australia.
⁴ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
⁵ Leiden University, Developmental and Educational Psychology, Leiden, the Netherlands.
⁶ Erasmus University Rotterdam, Erasmus School of Social and Behavioural Sciences, Rotterdam, the Netherlands.
⁷ University of Groningen, Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells & Systems, University Medical Center Groningen, Groningen, the Netherlands.
⁸ Philipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
⁹ Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
¹¹ Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen (UMG), Göttingen, Germany.
¹² Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.
¹³ Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, USA.
¹⁴ Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
¹⁵ German Center for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
¹⁶ Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.
¹⁷ Psychological Neuroscience Laboratory, Psychology Research Centre (CIPsi), School of Psychology, University of Minho, Braga, Portugal.
¹⁸ Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
¹⁹ University of Queensland, Institute for Molecular Bioscience, St. Lucia, QLD, Australia.
²⁰ Sorbonne University, Paris Brain Institute (ICM), CNRS, INRIA, INSERM, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
²¹ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²² Bielefeld University, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Department of Psychiatry, Bielefeld, Germany.
²³ Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
²⁴ School of Psychology and Counseling, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.
²⁵ Department of Psychology, School of Health and Psychological Sciences, City, University of London, London, UK.
²⁶ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁷ University of East London, School of Psychology, London, UK.
²⁸ Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁹ FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
³⁰ CIBERSAM ISCIII, Madrid, Spain.
³¹ Clinical Psychopharmacology Group, Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
³² SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
³³ Mercer University School of Medicine Department of Psychiatry and Behavioral Sciences Macon GA, Macon, USA.
³⁴ Department of Psychology, Stanford University, Stanford, USA.
³⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁶ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³⁷ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
³⁸ Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada.
³⁹ University Clinic for Radiology, University of Münster, Münster, Germany.
⁴⁰ Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
⁴¹ Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁴² Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴³ Core-Facility Brainimagin, Faculty of Medicine, University of Marburg, Marburg, Germany.
⁴⁴ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴⁵ Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
⁴⁶ Cardiff University Brain Research Imaging Center (CUBRIC), Cardiff University, Maindy Road, Cardiff, UK.
⁴⁷ Department of Psychology, University of Bath, Claverton Down, Bath, UK.
⁴⁸ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁴⁹ Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Halle-Jena-, Magdeburg, Germany.
⁵⁰ Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
⁵¹ IWK Health, NS, Halifax, Canada.
⁵² Department of Psychiatry, Dalhousie University, Halifax, Canada.
⁵³ School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
⁵⁴ QIMR Berghofer Medical Research Institute, Herston, Australia.
⁵⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.
⁵⁶ Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.
⁵⁷ German Center for Mental Health (DZPG), partner site Halle-Jena-, Magdeburg, Germany.
⁵⁸ Origami Lab, Montreal Neurological Institute, McGill, Canada.
⁵⁹ Mental Health Research Group, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain.
⁶⁰ Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
⁶¹ Department of Psychology, University of Halle, Halle, Germany.
⁶² German Center of Mental Health - Halle Site, Halle, Germany.
⁶³ Amsterdam University Medical Centers, location AMC, department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands.
⁶⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
⁶⁵ Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁶⁷ Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁶⁸ West Region, Institute of Mental Health, Singapore, Singapore.
⁶⁹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷⁰ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁷¹ SAMRC Unit on Risk & Resilience, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁷² University Medical Center Groningen, Cognitive Neuroscience Center, University of Groningen, Groningen, the Netherlands.
⁷³ Department of Psychiatry, Muğla Training and Research Hospital, Muğla, Turkey.
⁷⁴ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁵ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
⁷⁶ Intelligent Data Analysis Laboratory, Department of Electronic Engineering, University of Valencia (UV), Valencia, Spain.
⁷⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁷⁸ Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute of Neurosciences, UCSF School of Medicine, San Francisco, USA.
⁸⁰ Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands.
⁸¹ Amsterdam Neuroscience, Brain Imaging program, Amsterdam, Netherlands.
⁸² Orygen, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
⁸³ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia. lianne.schmaal@unimelb.edu.au.

^# Contributed equally.

PMID: 41184571
PMCID: PMC12602329
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

Chaira Serrarens et al. Mol Psychiatry. 2025 Dec.

. 2025 Dec;30(12):5625-5636.

doi: 10.1038/s41380-025-03310-8. Epub 2025 Nov 3.

Authors

Affiliations

¹ Department of Psychiatry and Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
² Changes GGZ, Breda, the Netherlands.
³ Orygen, Parkville, VIC, Australia.
⁴ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
⁵ Leiden University, Developmental and Educational Psychology, Leiden, the Netherlands.
⁶ Erasmus University Rotterdam, Erasmus School of Social and Behavioural Sciences, Rotterdam, the Netherlands.
⁷ University of Groningen, Cognitive Neuroscience Center, Department of Biomedical Sciences of Cells & Systems, University Medical Center Groningen, Groningen, the Netherlands.
⁸ Philipps-Universität Marburg, Faculty of Medicine, Department of Psychiatry and Psychotherapy, Marburg, Germany.
⁹ Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
¹¹ Laboratory of Systems Neuroscience and Imaging in Psychiatry (SNIP-Lab), University Medical Center Göttingen (UMG), Göttingen, Germany.
¹² Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.
¹³ Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, USA.
¹⁴ Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
¹⁵ German Center for Cardiovascular Research, Partner Site Greifswald, Greifswald, Germany.
¹⁶ Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.
¹⁷ Psychological Neuroscience Laboratory, Psychology Research Centre (CIPsi), School of Psychology, University of Minho, Braga, Portugal.
¹⁸ Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
¹⁹ University of Queensland, Institute for Molecular Bioscience, St. Lucia, QLD, Australia.
²⁰ Sorbonne University, Paris Brain Institute (ICM), CNRS, INRIA, INSERM, AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
²¹ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²² Bielefeld University, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Department of Psychiatry, Bielefeld, Germany.
²³ Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
²⁴ School of Psychology and Counseling, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.
²⁵ Department of Psychology, School of Health and Psychological Sciences, City, University of London, London, UK.
²⁶ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁷ University of East London, School of Psychology, London, UK.
²⁸ Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁹ FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain.
³⁰ CIBERSAM ISCIII, Madrid, Spain.
³¹ Clinical Psychopharmacology Group, Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
³² SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, Izmir, Turkey.
³³ Mercer University School of Medicine Department of Psychiatry and Behavioral Sciences Macon GA, Macon, USA.
³⁴ Department of Psychology, Stanford University, Stanford, USA.
³⁵ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁶ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
³⁷ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
³⁸ Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada.
³⁹ University Clinic for Radiology, University of Münster, Münster, Germany.
⁴⁰ Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
⁴¹ Department of Psychiatry and Neurosciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁴² Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴³ Core-Facility Brainimagin, Faculty of Medicine, University of Marburg, Marburg, Germany.
⁴⁴ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁴⁵ Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
⁴⁶ Cardiff University Brain Research Imaging Center (CUBRIC), Cardiff University, Maindy Road, Cardiff, UK.
⁴⁷ Department of Psychology, University of Bath, Claverton Down, Bath, UK.
⁴⁸ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁴⁹ Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Halle-Jena-, Magdeburg, Germany.
⁵⁰ Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
⁵¹ IWK Health, NS, Halifax, Canada.
⁵² Department of Psychiatry, Dalhousie University, Halifax, Canada.
⁵³ School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
⁵⁴ QIMR Berghofer Medical Research Institute, Herston, Australia.
⁵⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.
⁵⁶ Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, USA.
⁵⁷ German Center for Mental Health (DZPG), partner site Halle-Jena-, Magdeburg, Germany.
⁵⁸ Origami Lab, Montreal Neurological Institute, McGill, Canada.
⁵⁹ Mental Health Research Group, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain.
⁶⁰ Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
⁶¹ Department of Psychology, University of Halle, Halle, Germany.
⁶² German Center of Mental Health - Halle Site, Halle, Germany.
⁶³ Amsterdam University Medical Centers, location AMC, department of Radiology and Nuclear Medicine, Amsterdam, the Netherlands.
⁶⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
⁶⁵ Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶⁶ Max Planck Institute of Psychiatry, Munich, Germany.
⁶⁷ Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
⁶⁸ West Region, Institute of Mental Health, Singapore, Singapore.
⁶⁹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷⁰ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁷¹ SAMRC Unit on Risk & Resilience, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁷² University Medical Center Groningen, Cognitive Neuroscience Center, University of Groningen, Groningen, the Netherlands.
⁷³ Department of Psychiatry, Muğla Training and Research Hospital, Muğla, Turkey.
⁷⁴ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁷⁵ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
⁷⁶ Intelligent Data Analysis Laboratory, Department of Electronic Engineering, University of Valencia (UV), Valencia, Spain.
⁷⁷ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁷⁸ Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute of Neurosciences, UCSF School of Medicine, San Francisco, USA.
⁸⁰ Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands.
⁸¹ Amsterdam Neuroscience, Brain Imaging program, Amsterdam, Netherlands.
⁸² Orygen, Parkville, VIC, Australia. lianne.schmaal@unimelb.edu.au.
⁸³ Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia. lianne.schmaal@unimelb.edu.au.

^# Contributed equally.

PMID: 41184571
PMCID: PMC12602329
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.

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Conflict of interest statement

Competing interests: PMT and NJ received partial grant support from Biogen, Inc., for research unrelated to this manuscript. DJS has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. HJG has received travel grants and speaker honoraria from Fresenius Medical Care, Neuraxpharm, Servier, Indorsia, and Janssen Cilag as well as research funding from Fresenius Medical Care.

Figures

**Fig. 1. Effect sizes for subcortical volume regions showing significant group-by-age interaction effects and main effect of group.**
Effect sizes for volume of the (A) thalamus and lateral ventricles showing a significant group-by-age (AD, nAD and HC group) interaction effect and of the (B) hippocampus showing a significant main effect of group. AD: cases with current AD use; nAD: cases not currently taking AD; HC: healthy controls.

**Fig. 2. Effect sizes for cortical thickness regions showing significant group-by-age interaction effects and main effect of group.**
Effect sizes for (A) significant group-by-age (AD, nAD and HC group) interaction effects and (B) significant main effect of group on cortical thickness regions, plotted on the right hemisphere. AD: cases with current AD use; nAD: cases not currently taking AD; HC: healthy controls.

**Fig. 3. Effect sizes for cortical surface area regions showing significant group-by-age interaction effects and main effect of group.**
Effect sizes for surface area of the (A) insula and lateral occipital cortex showing a significant group-by-age (AD, nAD and HC group) interaction effect and of the (B) isthmus cingulate cortex showing a significant main effect of group, plotted on the right hemisphere. AD: cases with current AD use; nAD: cases not currently taking AD; HC: healthy controls.

**Fig. 4. Significant group-by-age interaction effects on mean thickness of the middle temporal gyrus and inferior frontal gyrus (pars triangularis).**
Mean cortical thickness for these regions is presented corrected for sex (estimated marginal means). HC: Healthy controls; nAD: cases not currently taking AD; AD: cases with current AD use.

**Fig. 5. Effects sizes for subcortical volume, cortical thickness, and cortical surface area regions showing a significant difference between groups.**
Effects sizes for subcortical volume, cortical thickness, and cortical surface area regions showing a significant difference between (A) AD-nAD individuals, (B) AD-HC individuals, and (C) nAD-HC individuals. Cortical thickness and cortical surface area regions showing a significant difference between groups are plotted on the right hemisphere. AD: cases with current AD use; nAD: cases not currently taking AD; HC: healthy controls.

**Fig. 6. Significant age-by-type of AD medication use interaction effect for mean cortical thickness of the rostral anterior cingulate cortex.**
Mean cortical thickness for this region is presented corrected for sex (estimated marginal means). SNRI: Selective serotonin and noradrenalin reuptake inhibitor; SSRI: Selective serotonin reuptake inhibitor.

See this image and copyright information in PMC

References

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

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

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Conflict of interest statement

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