No alterations of brain structural asymmetry in major depressive disorder: An ENIGMA consortium analysis

Carolien G.F. De Kovel, Lyubomir Aftanas, André Aleman, Aaron F. Alexander-Bloch, Bernhard T. Baune, Ivan Brack, Robin Bülow, Geraldo Busatto Filho, Angela Carballedo, Colm G. Connolly, Kathryn R. Cullen, Udo Dannlowski, Christopher G. Davey, Danai Dima, Katharina Dohm, Tracy Erwin-Grabner, Thomas Frodl, Cynthia H.Y. Fu, Geoffrey B. Hall, David C. GlahnBeata Godlewska, Ian H. Gotlib, Roberto Goya-Maldonado, Hans Jörgen Grabe, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Mathew A. Harris, Ben J. Harrison, Sean N. Hatton, Ian B. Hickie, Tiffany C. Ho, Neda Jahanshad, Tilo Kircher, Bernd Krämer, Axel Krug, Jim Lagopoulos, Elisabeth J. Leehr, Meng Li, Frank P. MacMaster, Glenda MacQueen, Andrew M. McIntosh, Quinn McLellan, Sarah E. Medland, Bryon A. Mueller, Igor Nenadic, Evgeny Osipov, Martina Papmeyer, Maria J. Portella, Liesbeth Reneman, Pedro G.P. Rosa, Matthew D. Sacchet, Knut Schnell, Anouk Schrantee, Kang Sim, Egle Simulionyte, Lisa Sindermann, Aditya Singh, Dan J. Stein, Benjamin N. Ubani, Nic J.A. Van Der Wee, Steven J.A. Van Der Werff, Ilya M. Veer, Yolanda Vives-Gilabert, Henry Völzke, Henrik Walter, Martin Walter, Melinda Westlund Schreiner, Heather Whalley, Nils Winter, Katharina Wittfeld, Tony T. Yang, Dilara Yüksel, Dario Zaremba, Paul M. Thompson, Dick J. Veltman, Lianne Schmaal, Clyde Francks

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects. Methods: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processedwith a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1. Results: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. Conclusions: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

Original languageEnglish (US)
Pages (from-to)1039-1049
Number of pages11
JournalAmerican Journal of Psychiatry
Volume176
Issue number12
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
Sackler Trust. Dr. Sacchet reports a financial relationship with Vorso Corp. Dr. Stein has received research grants and/or consultancy honoraria from Lundbeck and Sun. Dr. Thompson has received research grant support from Biogen.

Funding Information:
Dr. de Kovel and Dr. Francks were funded by the Max Planck Society (Germany). In addition, the work presented here was supported by various funding sources: the ENIGMA Major Depressive Disorder Working Group received support from NIH Big Data to Knowledge (BD2K; award U54 EB020403 to Dr. Thompson) and NIH (grant R01 MH116147 to Dr. Thompson). Dr. Schmaal is supported by a National Health and Medical Research Council Medical Research Future Fund Career Development Fellowship (APP1140764). The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. MRI scans in SHIP and SHIP-TREND (the second SHIP cohort) have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. This work was also funded by the German Research Foundation (DFG: GR 1912/5-1). The Effects of Psychotropic Drugs On Developing Brain-methylphenidate and fluoxetine (ePODPharmo) work was supported by 11.32050.26 ERA-NET PRIOMED CHILD FP 6 (EU) and by faculty resources from the University of Amsterdam. Additional funding was received from NIH (grants R01MH085734 and R21AT009173 to Dr. Yang; grant K01MH117442 to Dr. Ho), the University of California, San Francisco, Research Evaluation and Allocation Committee (Dr. Yang), and the Brain and Behavior Research Foundation (Young Investigator Award to Dr. Yang). The research at Melbourne was supported by the National Health and Medical Research Council of Australia (project grants 1024570 [principal investigator, Dr. Davey] and 1064643 [principal investigator, Dr.Harrison]). The research at Novosibirsk was supported by the Russian Science Foundation (grant 16-15-00128 to Dr. Aftanas). The study at Barcelona was funded by two grants of the Fondo de Investigaci?n Sanitaria (PI 10/00372, 13/1057) from the Instituto de Salud Carlos III, by the Centro de Investigaci?n Biom?dica en Red de SaludMental (CIBERSAM).Dr. Portella is funded throughMiguel Servet research contract (CP16-0020), co-financed by the European Regional Development Fund (2016-2019). The study at Magdeburg was funded by SFB 779 (Dr. M. Walter). The study at Minnesota was funded by NIMH grant K23MH090421, the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (grant P41 RR008079 to the Center for Magnetic Resonance Research; Dr. Cullen). The work at DIP-Groningen was funded by the Gratama Foundation, the Netherlands (to Dr. Groenewold). The work at For2017 and Muenster Neuroimaging Cohort was funded by the German Research Foundation (DFG, grants FOR2107 DA1151/5-1 and DA1151/5-2 to Dr. Dannlowski; KI588/14-1, KI588/15-1, KI588/14-2, and KI588/15-2 to Dr.Kircher; KR3822/5-1 to Dr.Krug), and also by the German Research Foundation (DFG; SFB-TRR58, Projects C09 and Z02 to Dr. Dannlowski) and the Interdisciplinary Center for Clinical Research of the medical faculty of M?nster (grant Dan3/012/17 to Dr. Dannlowski). The work at Oxford was supported by the Medical Research Council (grant MR/K022202 to Dr. Godlewska). The work in Singapore was supported by the National Healthcare Group (grant SIG/15012 to Dr. Sim). The work at fMRI Biomarkers in Affective Disorders (AFFDIS) was supported by the UMG Starting Grant and by the German Federal Ministry of Education and Research (BMBF: 01ZX1507, "PreNeSt - e:Med"). The research leading to the Bipolar Family Study results received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 602450. This work was also supported by Wellcome Trust Strategic Award 104036/Z/14/Z and the IMAGEMEND grant. Dr. Grabe has received research support from the German Research Foundation, the Federal Ministry of Education and Research, and the DAMP Foundation. Dr. MacMaster was funded by Alberta Children's Hospital Foundation, Branch Out Neurological Foundation. Dr. Medland is supported by a National Health and Medical Research Council senior research fellowship (APP1103623). Dr. Stein is funded by the SA Medical Research Council.

Funding Information:
Send correspondence to Dr. Francks (clyde.francks@mpi.nl). Dr. de Kovel and Dr. Francks were funded by the Max Planck Society (Germany). In addition, the work presented here was supported by various funding sources: the ENIGMA Major Depressive Disorder Working Group received support from NIH Big Data to Knowledge (BD2K; award U54 EB020403 to Dr. Thompson) and NIH (grant R01 MH116147 to Dr. Thompson). Dr. Schmaal is supported by a National Health and Medical Research Council Medical Research Future Fund Career Development Fellowship (APP1140764). The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg–West Pomerania. MRI scans in SHIP and SHIP-TREND (the second SHIP cohort) have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. This work was also funded by the German Research Foundation (DFG: GR 1912/5-1). The Effects of Psychotropic Drugs On Developing Brain–methylphenidate and fluoxetine (ePOD-Pharmo) work was supported by 11.32050.26 ERA-NET PRIOMED CHILD FP 6 (EU) and by faculty resources from the University of Amsterdam. Additional funding was received from NIH (grants R01MH085734 and R21AT009173 to Dr. Yang; grant K01MH117442 to Dr. Ho), the University of California, San Francisco, Research Evaluation and Allocation Committee (Dr. Yang), and the Brain and Behavior Research Foundation (Young Investigator Award to Dr. Yang). The research at Melbourne was supported by the National Health and Medical Research Council of Australia (project grants 1024570 [principal investigator, Dr. Davey] and 1064643 [principal investigator, Dr. Harrison]). The research at Novosibirsk was supported by the Russian Science Foundation (grant 16-15-00128 to Dr. Aftanas). The study at Barcelona was funded by two grants of the Fondo de Investigación Sanitaria (PI 10/00372, 13/1057) from the Instituto de Salud Carlos III, by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Dr. Portella is funded through Miguel Servet research contract (CP16-0020), co-financed by the European Regional Development Fund (2016–2019). The study at Magdeburg was funded by SFB 779 (Dr. M. Walter). The study at Minnesota was funded by NIMH grant K23MH090421, the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (grant P41 RR008079 to the Center for Magnetic Resonance Research; Dr. Cullen). The work at DIP-Groningen was funded by the Gratama Foundation, the Netherlands (to Dr. Groenewold). The work at For2017 and Muenster Neuroimaging Cohort was funded by the German Research Foundation (DFG, grants FOR2107 DA1151/5-1 and DA1151/5-2 to Dr. Dannlowski; KI588/14-1, KI588/15-1, KI588/14-2, and KI588/15-2toDr.Kircher;KR3822/5-1toDr.Krug),andalsobytheGerman Research Foundation (DFG; SFB-TRR58, Projects C09 and Z02 to Dr. Dannlowski) and the Interdisciplinary Center for Clinical Research of the medical faculty of Münster (grant Dan3/012/17 to Dr. Dannlowski). The work at Oxford was supported by the Medical Research Council (grant MR/ K022202 to Dr. Godlewska). The work in Singapore was supported by the National Healthcare Group (grant SIG/15012 to Dr. Sim). The work at fMRI Biomarkers in Affective Disorders (AFFDIS) was supported by the UMG Starting Grant and by the German Federal Ministry of Education and Research (BMBF: 01ZX1507, “PreNeSt - e:Med”). The research leading to the Bipolar Family Study results received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement 602450. This work was also supported by Wellcome Trust Strategic Award 104036/Z/14/Z and the IMAGEMEND grant. Dr. Grabe has received research support from the German Research Foundation, the Federal Ministry of Education and Research, and the DAMP Foundation. Dr. MacMaster was funded by Alberta Children’s Hospital Foundation, Branch Out Neurological Foundation. Dr. Medland is supported by a National Health and Medical Research Council senior research fellowship (APP1103623). Dr. Stein is funded by the SA Medical Research Council. Dr. Bülow has received travel grants and speaker honoraria from Bayer Healthcare AG. Dr. Godlewska has received travel grants from Janssen. Dr. Grabe has received travel grants or speakers honoraria from Fresenius Medical Care, Neuraxpharm, and Janssen-Cilag. Dr. Harris has received funding from the Dr. Mortimer and Theresa Sackler Foundation. Dr. Jahanshad is has received research support from Biogen. Dr. McIntosh has received research support funding from Eli Lilly, Janssen, and the

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© 2019 American Psychiatric Association. All rights reserved.

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