Transdiagnostic alterations in white matter microstructure associated with suicidal thoughts and behaviours in the ENIGMA Suicidal Thoughts and Behaviours consortium

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we examined WM alterations associated with STBs. Data processing was standardised across sites, and resulting WM microstructure measures (fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity and radial diffusivity) for 24 WM tracts and one global measure were pooled across 40 cohorts. We compared these measures among individuals with a psychiatric diagnosis and lifetime history of suicide attempt (n = 652; mean age = 35.4 ± 14.7; female = 71.8%), individuals with a psychiatric diagnosis but no STB (i.e., clinical controls; n = 1871; mean age = 34 ± 14.8; female = 59.8%), and individuals with no psychiatric diagnosis and no STB (i.e., healthy controls; n = 642; mean age = 29.6 ± 13.1; female = 62.9%). We also compared these measures among individuals with recent suicidal ideation (n = 714; mean age = 36.3 ± 15.3; female = 66.1%), clinical controls (n = 1184; mean age = 36.8 ± 15.6; female = 63.1%), and healthy controls (n = 1240; mean age = 31.6 ± 15.5; female = 61.0%). We found subtle but statistically significant effects, such as lower FA associated with a history of suicide attempt, over and above the effect of psychiatric diagnoses. These effects were strongest in the corona radiata, thalamic radiation, fornix/stria terminalis, corpus callosum and superior longitudinal fasciculus. Recent suicidal ideation was associated with higher AD in the cingulum. Effect sizes were small (partial eta-squared < 0.015). This large-scale coordinated mega-analysis revealed subtle regional and global alterations in WM microstructure in individuals with a history of suicide attempt and recent suicidal ideation. Longitudinal studies are needed to confirm whether these alterations are a risk factor for suicidal behaviour or ideation.

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Journal
Translational Psychiatry
Published
2025-10-24
DOI
https://doi.org/10.1038/s41398-025-03602-1
Primary Topic
Advanced Neuroimaging Techniques and Applications
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article
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article

Transdiagnostic alterations in white matter microstructure associated with suicidal thoughts and behaviours in the ENIGMA Suicidal Thoughts and Behaviours consortium

Zuriel Ceja, Fabrício Pereira, Martin Walter, Kathryn R. Cullen et al.
Translational Psychiatry
Advanced Neuroimaging Techniques and Applications
article

Transdiagnostic alterations in white matter microstructure associated with suicidal thoughts and behaviours in the ENIGMA Suicidal Thoughts and Behaviours consortium

Zuriel Ceja, Fabrício Pereira, Martin Walter, Kathryn R. Cullen, Alexander S. Hatoum, Anne‐Laura van Harmelen, Elizabeth D. Ballard, Lianne Schmaal, Mon‐Ju Wu, Andrew Mark McIntosh, Baptiste Couvy‐Duchesne, Federica Piras, Rosa Ayesa‐Arriola, Tomáš Hájek, Negar Fani, Martin Alda, Yoshiyuki Hirano, Ingrid Agartz, Lauren E. Salminen, Elisabeth Johanna Leehr, Hannah S. Savage, Miguel E. Rentería, Neda Jahanshad, Melissa Klug, Lejla Čolić, Naomi P. Friedman, Colm G. Connolly, Rafael Romero-García, Dominik Grotegerd, Frank Iorfino, Susanne L. Meinert, Niousha Dehestani, Romain Valabrègue, Fabrizio Piras, Benedicto Crespo‐Facorro, Benson Mwangi, Romain Colle, Fabrice Jollant, Manuel Canal‐Rivero, Ivan I. Maximov, Johanna Valencia‐Echeverry, Nic J.A. van der Wee, Francesco Benedetti, Yuki Ikemizu, Elisa Melloni, Stener Nerland, Lorielle M. F. Dietze, Kees van Heeringen, Sheri‐Michelle Koopowitz, Laura S. van Velzen, Jochen Bauer, Andrew E. Reineberg, Giovana Zunta‐Soares, Benjamin Straube, Tiffany Cheing Ho, Florian Thomas‐Odenthal, Nina Alexander, Yara J. Toenders, Gloria Roberts, Eiji Shimizu, Elizabeth Lippard, Maria R. Dauvermann, Ian H. Gotlib, J. Douglas Steele, Víctor Ortiz‐García de la Foz, Igor Nenadić, Zeynep Başgöze, Jérémy Deverdun, Frederike Stein, Luca M. Villa, Ana M. Díaz‐Zuluaga, Carl M. Sellgren, Carlos López‐Jaramillo, Alyssa H. Zhu, Paula Usemann, Klaus Berger, Udo Dannlowski, Tilo T. J. Kircher, Andrea Parolin Jackowski, Nynke A. Groenewold, Ian Bernard Hickie, Émilie Olié, Hilary P. Blumberg, Gordon D. Waiter, Simon Červenka, Philippe Courtet, Dan Joseph Stein, Anna Kraus, Giovanni Abrahão Salum, Sanne J.H. van Rooij, Marco Hermesdorf, Harry R. Smolker, Carlotta Barkhau, Emmanuelle Corruble, Axel Krug, Katharina Brosch, André Zugman, Sara Poletti, Bianca Besteher, Gerd Wagner, Anca‐Larisa Sandu, Sean R. McWhinney, Jair C. Soares, Jonathan Ipser, Heather C. Whalley, Katie A. McLaughlin, Lea Teutenberg, Pedro Mário Pan, Nerisa Banaj, Meng Li, Adrián I. Campos, Matthew D. Sacchet, Philip Bowden Mitchell, Tony T. Yang, Jennifer W. Evans, Paul M. Thompson, Y. Isobe, Carlos A. Zarate, Kira Flinkenflügel
article en

Abstract

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we examined WM alterations associated with STBs. Data processing was standardised across sites, and resulting WM microstructure measures (fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity and radial diffusivity) for 24 WM tracts and one global measure were pooled across 40 cohorts. We compared these measures among individuals with a psychiatric diagnosis and lifetime history of suicide attempt (n = 652; mean age = 35.4 ± 14.7; female = 71.8%), individuals with a psychiatric diagnosis but no STB (i.e., clinical controls; n = 1871; mean age = 34 ± 14.8; female = 59.8%), and individuals with no psychiatric diagnosis and no STB (i.e., healthy controls; n = 642; mean age = 29.6 ± 13.1; female = 62.9%). We also compared these measures among individuals with recent suicidal ideation (n = 714; mean age = 36.3 ± 15.3; female = 66.1%), clinical controls (n = 1184; mean age = 36.8 ± 15.6; female = 63.1%), and healthy controls (n = 1240; mean age = 31.6 ± 15.5; female = 61.0%). We found subtle but statistically significant effects, such as lower FA associated with a history of suicide attempt, over and above the effect of psychiatric diagnoses. These effects were strongest in the corona radiata, thalamic radiation, fornix/stria terminalis, corpus callosum and superior longitudinal fasciculus. Recent suicidal ideation was associated with higher AD in the cingulum. Effect sizes were small (partial eta-squared < 0.015). This large-scale coordinated mega-analysis revealed subtle regional and global alterations in WM microstructure in individuals with a history of suicide attempt and recent suicidal ideation. Longitudinal studies are needed to confirm whether these alterations are a risk factor for suicidal behaviour or ideation.

Translational PsychiatryVol. 15(1)
Florida State University (US), South African Medical Research Council (ZA), University of Fukui (JP), University of Southern California (US), Leiden University (NL), Uppsala University (SE), Centre National de la Recherche Scientifique (FR), The University of Sydney (AU), Dalhousie University (CA), National Institutes of Health (US), Universidade Federal do Rio Grande do Sul (BR), Universidad de Cantabria (ES), Feinstein Institute for Medical Research (US), Harvard University (US), Deakin University (AU), Emory University (US), Vita-Salute San Raffaele University (IT), Inserm (FR), University of Cape Town (ZA), Chiba University (JP), Philipps University of Marburg (DE), University of California, Los Angeles (US), The University of Queensland (AU), The University of Melbourne (AU), University of Dundee (GB), Western Norway University of Applied Sciences (NO), University of California, San Francisco (US), University of Oregon (US), University of Oslo (NO), Regeneron (United States) (US), University of Colorado Boulder (US), University of Aberdeen (GB), Université de Montpellier (FR), Østfold University of Applied Sciences (NO), Washington University in St. Louis (US), QIMR Berghofer Medical Research Institute (AU), University of Münster (DE), University of Cambridge (GB), Université Paris-Saclay (FR), University Hospital Bonn (DE), Leiden University Medical Center (NL), Ghent University Hospital (BE), Instituto de Salud Carlos III (ES), Edinburgh Cancer Research (GB), Karolinska Institutet (SE), UNSW Sydney (AU), Yale University (US), Universidad de Antioquia (CO), Sorbonne Université (FR), Massachusetts General Hospital (US), Centro de Investigación Biomédica en Red de Salud Mental (ES), Orygen Youth Health (AU), Hospital de Clínicas de Porto Alegre (BR), Assistance Publique – Hôpitaux de Paris (FR), Marqués de Valdecilla University Hospital (ES), Neurobehavioral Systems (US), Child Mind Institute (US), University Hospital Münster (DE), Centre de recherche en Epidémiologie et Santé des Populations (FR), Hôpital Gui de Chauliac (FR), Orygen (AU), Instituto de Investigación Marqués de Valdecilla (ES), Brain (Germany) (DE), Institut de Myologie (FR), Fondation de l'Avenir (FR), Diakonhjemmet Hospital (NO), Hôpital Lapeyronie (FR), Instituto de Biomedicina de Sevilla (ES), Jena University Hospital (DE), University of Minnesota Medical Center (US), Stockholm Health Care Services (SE), University Hospital Magdeburg (DE), Fondazione Santa Lucia (IT), Institut du Cerveau (FR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Hospital Universitario Virgen del Rocío (ES), National Institute of Mental Health (US), The University of Texas Health Science Center (US), Center for Forensic Mental Health, Chiba University (JP), Bicêtre Hospital (FR), Hôpital Paul-Brousse (FR), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), McGill University (CA), Université de Nîmes (FR), University of Birmingham (GB), The University of Texas at Austin (US), Universidade Federal de São Paulo (BR), Erasmus University Rotterdam (NL), The University of Texas Health Science Center at Houston (US), Stanford University (US), University of Edinburgh (GB)
Bill and Melinda Gates Foundation, Brain and Behavior Research Foundation, American Foundation for Suicide Prevention, John S. Dunn Foundation, University of Minnesota, Universidad de Sevilla, Japan Agency for Medical Research and Development, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Scottish Government, University of Texas Health Science Center at Houston, Nova Scotia Health Research Foundation, Scottish Funding Council, European Commission, South African Medical Research Council, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Universiteit Leiden, Bundesministerium für Bildung und Forschung, Dalhousie University, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministerio de Ciencia e Innovación, Junta de Andalucía, Instituto de Investigación Marqués de Valdecilla, National Institutes of Health, University of California, San Francisco, Chief Scientist Office, Scottish Government Health and Social Care Directorate, Canadian Institutes of Health Research, Medical Research Council, Engineering and Physical Sciences Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, National Institute of Mental Health, National Center for Advancing Translational Sciences, National Center for Complementary and Integrative Health, Weill Institute for Neurosciences, University of California, San Francisco
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Advanced Neuroimaging Techniques and Applications
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