Abstract
Background: Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior. Methods: Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects. Results: We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe. Conclusions: This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.
Original language | English |
---|---|
Pages (from-to) | 243-252 |
Number of pages | 10 |
Journal | Biological Psychiatry |
Volume | 90 |
Issue number | 4 |
DOIs | |
Publication status | Published - 15 Aug 2021 |
Keywords
- Major depressive disorder
- Structural magnetic resonance imaging
- Suicide attempt
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In: Biological Psychiatry, Vol. 90, No. 4, 15.08.2021, p. 243-252.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts
AU - Campos, Adrian I.
AU - Thompson, Paul M.
AU - Veltman, Dick J.
AU - Pozzi, Elena
AU - van Veltzen, Laura S.
AU - Jahanshad, Neda
AU - Adams, Mark J.
AU - Baune, Bernhard T.
AU - Berger, Klaus
AU - Brosch, Katharina
AU - Bülow, Robin
AU - Connolly, Colm G.
AU - Dannlowski, Udo
AU - Davey, Christopher G.
AU - de Zubicaray, Greig I.
AU - Dima, Danai
AU - Erwin-Grabner, Tracy
AU - Evans, Jennifer W.
AU - Fu, Cynthia H. Y.
AU - Gotlib, Ian H.
AU - Goya-Maldonado, Roberto
AU - Grabe, Hans J.
AU - Grotegerd, Dominik
AU - Harris, Matthew A.
AU - Harrison, Ben J.
AU - Hatton, Sean N.
AU - Hermesdorf, Marco
AU - Hickie, Ian B.
AU - Ho, Tiffany C.
AU - Kircher, Tilo
AU - Krug, Axel
AU - Lagopoulos, Jim
AU - Lemke, Hannah
AU - McMahon, Katie
AU - MacMaster, Frank P.
AU - Martin, Nicholas G.
AU - McIntosh, Andrew M.
AU - Medland, Sarah E.
AU - Meinert, Susanne
AU - Meller, Tina
AU - Nenadic, Igor
AU - Opel, Nils
AU - Redlich, Ronny
AU - Reneman, Liesbeth
AU - Repple, Jonathan
AU - Sacchet, Matthew D.
AU - Schmitt, Simon
AU - Schrantee, Anouk
AU - ENIGMA-MDD Working Group
AU - Sim, Kang
AU - Schmaal, Lianne
AU - Singh, Aditya
N1 - Funding Information: HJG has received travel grants and speaker’s honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care. CAZ is a full-time U.S. government employee. He is listed as a coinventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. CAZ has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. NJ and PMT are MPI of a research-related grant from Biogen, Inc., for work unrelated to this manuscript. IBH is funded by NHMRC Fellowship (2013–2017 and 2018–2022). He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government–funded Project Synergy (2017–2020). All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: The work reported here was supported in part by many public and private agencies across the world. Core funding for ENIGMA was provided by the National Institutes of Health (NIH) Big Data to Knowledge (BD2K) program (Consortium Grant No. U54 EB020403 [to PMT]), the University Medical Center G?ttingen and the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF: 01 ZX 1507, ??PreNeSt - e:Med?? [to AFFDIS]), as well by support to the BiDirect study (BMBF; Grant Nos. FKZ-01ER0816 and FKZ-01ER1506), the ETPB study at the NIH (funded by the National Institute of Mental Health [NIMH] Intramural Program), the FOR2107 study (German Research Foundation: Grant Nos. Ki588/14-1 and Ki588/14-2 [to TK]), the IMH Singapore cohort (National Healthcare Group Research: Grant No. SIG/15012 [to KS]), the LOND study (supported in part by the Biomedical Research Centre, South London, and Maudsley NHS Foundation Trust, London, United Kingdom), the Stanford study (supported in part by the NIMH Grant R37-MH101495 [to IHG]), the Melbourne study (Australia's National Health and Medical Research Council [NHMRC] Project Grants 1064643 [to principal investigator, BJH] and 1024570 [to principal investigator, CGD]), the QTIM study (National Institute of Child Health and Human Development Grant No. R01-HD050735 and NHMRC Australia Grant Nos. 486682 and 1009064 [to principal investigator, MJW]), the Pharmo study in Amsterdam (faculty resources of the Academic Medical Center, University of Amsterdam, and 11.32050.26 ERA-NET PRIOMEDCHILD FP 6 [EU]), and the UCSF study (funded in part by the NIMH Grant Nos. R01MH085734 and K01MH117442 [to TTY and TCH]; National Center for Complementary and Integrative Health [NCCIH Grant No. 1R61AT009864]; and the American Foundation for Suicide Prevention [AFSP]). The Edinburgh group is funded by a Wellcome Trust Strategic Award ?Stratifying Resilience and Depression Longitudinally? (STRADL) (Reference 104036/Z/14/Z [to AMM]). The SHIP cohort is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg?West Pomerania. This work was also supported by a UQ Research Training Scholarship from The University of Queensland (UQ [to AIC]), the NHMRC and Australian Research Council (ARC) through a Research Fellowship (Grant No. APP1102821 [to MER]), NHMRC Career Development Fellowships (Grant Nos. 1124472 and 1061757, respectively [to BJH and CGD]), NHMRC (Grant Nos. APP1103623, APP1158127, and APP1172917 [to SEM]), NCCIH (Grant No. 1R61AT009864 [to TTY]), and the NIMH of the NIH (U.S.) under Award Number R01-MH117601 (to LS and NJ). MER and LS conceived and jointly supervised the study. Authors from all site cohorts were involved in data collection, processing, analysis, and funding for their samples. AIC implemented the analysis pipeline, performed all statistical analyses, and generated the tables and figures. AIC, MER, and LS drafted the first draft of the manuscript with feedback and input from all coauthors. All authors approved the content of this manuscript. A previous version of this article was published as a preprint on medRxiv: https://www.medrxiv.org/content/10.1101/2020.05.06.20090191v1. This project used data from the UK Biobank under application number 25331. HJG has received travel grants and speaker's honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag as well as research funding from Fresenius Medical Care. CAZ is a full-time U.S. government employee. He is listed as a coinventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. CAZ has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. NJ and PMT are MPI of a research-related grant from Biogen, Inc. for work unrelated to this manuscript. IBH is funded by NHMRC Fellowship (2013?2017 and 2018?2022). He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government?funded Project Synergy (2017?2020). All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: The work reported here was supported in part by many public and private agencies across the world. Core funding for ENIGMA was provided by the National Institutes of Health (NIH) Big Data to Knowledge (BD2K) program (Consortium Grant No. U54 EB020403 [to PMT] ), the University Medical Center Göttingen and the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF: 01 ZX 1507, ‘‘PreNeSt - e:Med’’ [to AFFDIS]), as well by support to the BiDirect study (BMBF; Grant Nos. FKZ-01ER0816 and FKZ-01ER1506), the ETPB study at the NIH (funded by the National Institute of Mental Health [NIMH] Intramural Program), the FOR2107 study (German Research Foundation: Grant Nos. Ki588/14-1 and Ki588/14-2 [to TK]), the IMH Singapore cohort (National Healthcare Group Research: Grant No. SIG/15012 [to KS]), the LOND study (supported in part by the Biomedical Research Centre, South London, and Maudsley NHS Foundation Trust, London, United Kingdom), the Stanford study (supported in part by the NIMH Grant R37-MH101495 [to IHG]), the Melbourne study (Australia’s National Health and Medical Research Council [NHMRC] Project Grants 1064643 [to principal investigator, BJH] and 1024570 [to principal investigator, CGD]), the QTIM study ( National Institute of Child Health and Human Development Grant No. R01-HD050735 and NHMRC Australia Grant Nos. 486682 and 1009064 [to principal investigator, MJW]), the Pharmo study in Amsterdam (faculty resources of the Academic Medical Center, University of Amsterdam, and 11.32050.26 ERA-NET PRIOMEDCHILD FP 6 [EU]), and the UCSF study (funded in part by the NIMH Grant Nos. R01MH085734 and K01MH117442 [to TTY and TCH]; National Center for Complementary and Integrative Health [NCCIH Grant No. 1R61AT009864]; and the American Foundation for Suicide Prevention [AFSP]). The Edinburgh group is funded by a Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z [to AMM]). The SHIP cohort is part of the Community Medicine Research Network of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg–West Pomerania. This work was also supported by a UQ Research Training Scholarship from The University of Queensland (UQ [to AIC]), the NHMRC and Australian Research Council (ARC) through a Research Fellowship (Grant No. APP1102821 [to MER]), NHMRC Career Development Fellowships (Grant Nos. 1124472 and 1061757, respectively [to BJH and CGD]), NHMRC (Grant Nos. APP1103623, APP1158127, and APP1172917 [to SEM]), NCCIH (Grant No. 1R61AT009864 [to TTY]), and the NIMH of the NIH (U.S.) under Award Number R01-MH117601 (to LS and NJ). Publisher Copyright: © 2021 Society of Biological Psychiatry Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/15
Y1 - 2021/8/15
N2 - Background: Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior. Methods: Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects. Results: We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe. Conclusions: This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.
AB - Background: Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior. Methods: Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects. Results: We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe. Conclusions: This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.
KW - Major depressive disorder
KW - Structural magnetic resonance imaging
KW - Suicide attempt
UR - http://www.scopus.com/inward/record.url?scp=85110547363&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.biopsych.2021.03.015
DO - https://doi.org/10.1016/j.biopsych.2021.03.015
M3 - Article
C2 - 34172278
SN - 0006-3223
VL - 90
SP - 243
EP - 252
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 4
ER -