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[Preprint]. 2024 Nov 7:2024.11.07.24316876.

doi: 10.1101/2024.11.07.24316876.

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

Laura S van Velzen^{1

2}, Lejla Colic^{3

4

5}, Zuriel Ceja^{6

7}, Maria R Dauvermann^{8

9}, Luca M Villa³, Hannah S Savage^{2

10}, Yara J Toenders^{1

2

11}, Niousha Dehestani^{10

12}, Alyssa H Zhu¹³, Adrian I Campos¹⁴, Lauren E Salminen¹³, Ingrid Agartz^{15

16

17}, Nina Alexander^{18

19}, Rosa Ayesa-Arriola²⁰, Elizabeth D Ballard²¹, Nerisa Banaj²², Carlotta Barkhau²³, Zeynep Başgöze²⁴, Jochen Bauer²⁵, Francesco Benedetti²⁶, Klaus Berger²⁷, Bianca Besteher^{4

5}, Katharina Brosch^{18

19

28}, Manuel Canal-Rivero^{29

30}, Simon Cervenka^{17

31}, Romain Colle³², Colm G Connolly³³, Emmanuelle Corruble³², Philippe Courtet^{34

35}, Baptiste Couvy-Duchesne^{36

37}, Benedicto Crespo-Facorro^{29

30

38}, Kathryn R Cullen²⁴, Udo Dannlowski²³, Jeremy Deverdun^{39

40}, Ana M Diaz-Zuluaga^{41

42}, Lorielle M F Dietze⁴³, Jennifer W Evans²¹, Negar Fani⁴⁴, Kira Flinkenflügel²³, Naomi P Friedman⁴⁵, Ian H Gotlib⁴⁶, Nynke A Groenewold⁴⁷, Dominik Grotegerd²³, Tomas Hajek⁴³, Alexander S Hatoum⁴⁸, Marco Hermesdorf²⁷, Ian B Hickie⁴⁹, Yoshiyuki Hirano^{50

51}, Tiffany C Ho^{52

53}, Yuki Ikemizu^{50

54}, Frank Iorfino⁴⁹, Jonathan C Ipser⁴⁷, Yuko Isobe^{50

51}, Andrea P Jackowski^{55

56}, Fabrice Jollant^{57

58

59

32}, Tilo Kircher^{18

19}, Melissa Klug²³, Sheri-Michelle Koopowitz⁴⁷, Anna Kraus²³, Axel Krug^{18

60}, Emmanuelle Le Bars^{39

40}, Elisabeth J Leehr²³, Meng Li^{4

5}, Elizabeth T C Lippard^{61

62}, Carlos Lopez-Jaramillo⁴², Ivan I Maximov^{15

63}, Andrew M McIntosh⁶⁴, Katie A McLaughlin^{65

66}, Sean R McWhinney⁴³, Susanne Meinert^{23

67}, Elisa Melloni²⁶, Philip B Mitchell⁶⁸, Benson Mwangi^{69

70}, Igor Nenadić^{18

19}, Stener Nerland^{15

16}, Emilie Olie^{34

35}, Victor Ortiz-García de la Foz²⁰, Pedro M Pan⁵⁶, Fabricio Pereira^{71

72}, Fabrizio Piras²², Federica Piras²², Sara Poletti²⁶, Andrew E Reineberg⁷³, Gloria Roberts⁶⁸, Rafael Romero-García^{9

29}, Matthew D Sacchet⁷⁴, Giovanni A Salum^{75

76}, Anca-Larisa Sandu⁷⁷, Carl M Sellgren^{17

78}, Eiji Shimizu^{50

51

54}, Harry R Smolker⁷⁹, Jair C Soares^{69

70}, Gianfranco Spalletta^{22

80}, J Douglas Steele⁸¹, Frederike Stein^{18

19}, Dan J Stein⁸², Benjamin Straube^{18

19}, Lea Teutenberg^{18

19}, Florian Thomas-Odenthal^{18

19}, Paula Usemann^{18

19}, Romain Valabregue^{83

84}, Johanna Valencia-Echeverry⁴², Gerd Wagner^{4

85}, Gordon Waiter⁷⁷, Martin Walter^{4

5

86

87}, Heather C Whalley^{64

88}, Mon-Ju Wu^{69

70}, Tony T Yang⁸⁹, Carlos A Zarate²¹, Andre Zugman⁹⁰, Giovana B Zunta-Soares^{69

70}, Kees van Heeringen⁹¹, Sanne J H van Rooij⁴⁴, Nic van der Wee^{92

93}, Steven van der Werff^{92

93}, Paul M Thompson¹³, Hilary P Blumberg^{3

94

95}, Anne-Laura van Harmelen^{9

96}, Miguel E Rentería^{6

7}, Neda Jahanshad¹³; ENIGMA Suicidal Thoughts and Behaviours Consortium; Lianne Schmaal^{1

2}

Affiliations

¹ Orygen, Parkville, VIC, Australia.
² Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
³ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁴ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁵ DZPG (German Center for Mental Health), partner site Halle/Jena/Magdeburg.
⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁷ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁸ Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK.
⁹ Department of Psychiatry, University of Cambridge, Cambridge, UK.
¹⁰ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Victoria, Australia.
¹¹ Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, the Netherlands.
¹² School of Psychology, Deakin University, Victoria, Australia.
¹³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
¹⁴ Regeneron Genetics Center, Tarrytown, NY, USA.
¹⁵ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁶ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
¹⁷ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
¹⁸ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
¹⁹ Center for Mind, Brain, and Behavior (CMBB), University of Marburg, Marburg, Germany.
²⁰ Department of Psychiatry. Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.
²¹ Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda MD, USA.
²² Laboratory of Neuropsychiatry, Clinical Neuroscience and Neurorehabilitation Department, Santa Lucia Foundation IRCCS, Rome, Italy.
²³ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²⁴ Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA.
²⁵ Clinic for Radiology, University Hospital Münster, Münster, Germany.
²⁶ Division of Neuroscience, Psychiatry and Psychobiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁷ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
²⁸ Institute of Behavioral Sciences, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
²⁹ Instituto de Biomedicina de Sevilla (IBiS)/HUVR/CSIC/Universidad de Sevilla. CIBERSAM (ISCIII).
³⁰ Mental Health Service, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
³¹ Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden.
³² MOODS Team, INSERM 1018, CESP, Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France.
³³ Department of Biomedical Sciences, Florida State University, Tallahassee, FL.
³⁴ Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.
³⁵ IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.
³⁶ Institute for Molecular Bioscience, the University of Queensland, St Lucia, QLD, Australia.
³⁷ Sorbonne University, Paris Brain Institute - ICM, CNRS, Inria, Inserm, AP-HP, Hôpital de la Pitié Salpêtrière, F-75013, Paris, France.
³⁸ Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM), Madrid, Spain.
³⁹ Institut d'Imagerie Fonctionnelle Humaine, I2FH, Department of Neuroradiology, Gui de Chauliac Hospital and University of Montpellier, Montpellier, France.
⁴⁰ Department of Neuroradiology, Gui de Chauliac Hospital and University of Montpellier, Montpellier, France.
⁴¹ Center for Neurobehavioral Genetics,Semel Institute for Neuroscience and Behavior David Geffen School of Medicine, University of California Los Angeles.
⁴² Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Columbia.
⁴³ Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
⁴⁴ Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA.
⁴⁵ Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
⁴⁶ Department of Psychology, Stanford University, Stanford, CA 94305 USA.
⁴⁷ Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴⁸ Department of Psychological & Brain Sciences, Washington University in St. Louis.
⁴⁹ The University of Sydney, Sydney, Australia.
⁵⁰ Research Center for Child Mental Development, Chiba University.
⁵¹ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University and University of Fukui.
⁵² Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵³ Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA.
⁵⁴ Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University.
⁵⁵ Østfold University College Department of Education, ICT and Learning, Halden, Norway.
⁵⁶ Universidade Federal de São Paulo, Brazil.
⁵⁷ Faculty of medicine, University Paris-Saclay & Bicetre hospital, APHP, Le Kremlin-Bicetre, France.
⁵⁸ Department of psychiatry, CHU Nîmes, Nîmes, France.
⁵⁹ Department of psychiatry, McGill University, Montreal, Canada.
⁶⁰ Department of Psychiatry, University Hospital Bonn, Bonn, Germany.
⁶¹ Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas at Austin.
⁶² University of Texas at Austin.
⁶³ Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway.
⁶⁴ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
⁶⁵ Ballmer Institute for Children's Behavioral Health, University of Oregon.
⁶⁶ Department of Psychology, Harvard University.
⁶⁷ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁶⁸ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia.
⁶⁹ Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston.
⁷⁰ UTHealth Houston School of Behavioral Health Sciences.
⁷¹ MIPA, Université de Nîmes, Nimes, France.
⁷² Division for clinical research and innovation, University Hospital Center of Nimes, Nimes, France.
⁷³ Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
⁷⁴ Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷⁵ Child Mind Institute, New York.
⁷⁶ Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre - Porto Alegre, Brazil.
⁷⁷ Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK.
⁷⁸ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
⁷⁹ Institute for Cognitive Science, University of Colorado Boulder, Boulder, CO, USA.
⁸⁰ Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
⁸¹ Division of Imaging Science and Technology, Medical School, University of Dundee, Dundee UK.
⁸² SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town.
⁸³ Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
⁸⁴ Centre de Neuro-Imagerie de Recherche, CENIR, ICM, Paris, France.
⁸⁵ Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Jena-Magdeburg-Halle, Jena, Germany.
⁸⁶ Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany.
⁸⁷ Leibniz Institute for Neurobiology, Magdeburg, Germany.
⁸⁸ Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
⁸⁹ Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
⁹⁰ National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
⁹¹ Ghent University, Ghent, Belgium.
⁹² Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁹³ Leiden Institute for Brain and Cognition. Leiden University Medical Center, Leiden, The Netherlands.
⁹⁴ Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
⁹⁵ Child Study Center, Yale School of Medicine, New Haven, CT, USA.
⁹⁶ Education and Child Studies, Leiden University, Leiden, the Netherlands.

PMID: 39802789
PMCID: PMC11722476
DOI: 10.1101/2024.11.07.24316876

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

Laura S van Velzen et al. medRxiv. 2024.

[Preprint]. 2024 Nov 7:2024.11.07.24316876.

doi: 10.1101/2024.11.07.24316876.

Authors

Affiliations

¹ Orygen, Parkville, VIC, Australia.
² Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia.
³ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁴ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁵ DZPG (German Center for Mental Health), partner site Halle/Jena/Magdeburg.
⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁷ School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁸ Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK.
⁹ Department of Psychiatry, University of Cambridge, Cambridge, UK.
¹⁰ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Victoria, Australia.
¹¹ Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, the Netherlands.
¹² School of Psychology, Deakin University, Victoria, Australia.
¹³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
¹⁴ Regeneron Genetics Center, Tarrytown, NY, USA.
¹⁵ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁶ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
¹⁷ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
¹⁸ Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
¹⁹ Center for Mind, Brain, and Behavior (CMBB), University of Marburg, Marburg, Germany.
²⁰ Department of Psychiatry. Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.
²¹ Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda MD, USA.
²² Laboratory of Neuropsychiatry, Clinical Neuroscience and Neurorehabilitation Department, Santa Lucia Foundation IRCCS, Rome, Italy.
²³ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
²⁴ Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA.
²⁵ Clinic for Radiology, University Hospital Münster, Münster, Germany.
²⁶ Division of Neuroscience, Psychiatry and Psychobiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁷ Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
²⁸ Institute of Behavioral Sciences, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
²⁹ Instituto de Biomedicina de Sevilla (IBiS)/HUVR/CSIC/Universidad de Sevilla. CIBERSAM (ISCIII).
³⁰ Mental Health Service, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
³¹ Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden.
³² MOODS Team, INSERM 1018, CESP, Université Paris-Saclay, Faculté de Médecine Paris-Saclay, Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Saclay, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France.
³³ Department of Biomedical Sciences, Florida State University, Tallahassee, FL.
³⁴ Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.
³⁵ IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.
³⁶ Institute for Molecular Bioscience, the University of Queensland, St Lucia, QLD, Australia.
³⁷ Sorbonne University, Paris Brain Institute - ICM, CNRS, Inria, Inserm, AP-HP, Hôpital de la Pitié Salpêtrière, F-75013, Paris, France.
³⁸ Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM), Madrid, Spain.
³⁹ Institut d'Imagerie Fonctionnelle Humaine, I2FH, Department of Neuroradiology, Gui de Chauliac Hospital and University of Montpellier, Montpellier, France.
⁴⁰ Department of Neuroradiology, Gui de Chauliac Hospital and University of Montpellier, Montpellier, France.
⁴¹ Center for Neurobehavioral Genetics,Semel Institute for Neuroscience and Behavior David Geffen School of Medicine, University of California Los Angeles.
⁴² Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Columbia.
⁴³ Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
⁴⁴ Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA.
⁴⁵ Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
⁴⁶ Department of Psychology, Stanford University, Stanford, CA 94305 USA.
⁴⁷ Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴⁸ Department of Psychological & Brain Sciences, Washington University in St. Louis.
⁴⁹ The University of Sydney, Sydney, Australia.
⁵⁰ Research Center for Child Mental Development, Chiba University.
⁵¹ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University and University of Fukui.
⁵² Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵³ Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA.
⁵⁴ Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University.
⁵⁵ Østfold University College Department of Education, ICT and Learning, Halden, Norway.
⁵⁶ Universidade Federal de São Paulo, Brazil.
⁵⁷ Faculty of medicine, University Paris-Saclay & Bicetre hospital, APHP, Le Kremlin-Bicetre, France.
⁵⁸ Department of psychiatry, CHU Nîmes, Nîmes, France.
⁵⁹ Department of psychiatry, McGill University, Montreal, Canada.
⁶⁰ Department of Psychiatry, University Hospital Bonn, Bonn, Germany.
⁶¹ Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas at Austin.
⁶² University of Texas at Austin.
⁶³ Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway.
⁶⁴ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
⁶⁵ Ballmer Institute for Children's Behavioral Health, University of Oregon.
⁶⁶ Department of Psychology, Harvard University.
⁶⁷ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
⁶⁸ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia.
⁶⁹ Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston.
⁷⁰ UTHealth Houston School of Behavioral Health Sciences.
⁷¹ MIPA, Université de Nîmes, Nimes, France.
⁷² Division for clinical research and innovation, University Hospital Center of Nimes, Nimes, France.
⁷³ Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
⁷⁴ Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷⁵ Child Mind Institute, New York.
⁷⁶ Universidade Federal do Rio Grande do Sul, Hospital de Clinicas de Porto Alegre - Porto Alegre, Brazil.
⁷⁷ Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK.
⁷⁸ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
⁷⁹ Institute for Cognitive Science, University of Colorado Boulder, Boulder, CO, USA.
⁸⁰ Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
⁸¹ Division of Imaging Science and Technology, Medical School, University of Dundee, Dundee UK.
⁸² SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town.
⁸³ Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
⁸⁴ Centre de Neuro-Imagerie de Recherche, CENIR, ICM, Paris, France.
⁸⁵ Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (C-I-R-C), Jena-Magdeburg-Halle, Jena, Germany.
⁸⁶ Department of Psychiatry and Psychotherapy, University Tübingen, Tübingen, Germany.
⁸⁷ Leibniz Institute for Neurobiology, Magdeburg, Germany.
⁸⁸ Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
⁸⁹ Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
⁹⁰ National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
⁹¹ Ghent University, Ghent, Belgium.
⁹² Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
⁹³ Leiden Institute for Brain and Cognition. Leiden University Medical Center, Leiden, The Netherlands.
⁹⁴ Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
⁹⁵ Child Study Center, Yale School of Medicine, New Haven, CT, USA.
⁹⁶ Education and Child Studies, Leiden University, Leiden, the Netherlands.

PMID: 39802789
PMCID: PMC11722476
DOI: 10.1101/2024.11.07.24316876

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, axial diffusivity, mean diffusivity and radial diffusivity) for 25 WM tracts 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 mental disorder 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 fractional anisotropy 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. Effect sizes were small (Cohen's d < 0.25). Recent suicidal ideation was not associated with alterations in WM microstructure. This large-scale coordinated mega-analysis revealed subtle regional and global alterations in WM microstructure in individuals with a history of suicide attempt. Longitudinal studies are needed to confirm whether these alterations are a risk factor for suicidal behaviour.

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Conflict of interest statement

Conflicts of interest ALvH receives consultancy fees from the Augeo foundation. CAZ is a full-time US government employee. He is listed as a co-inventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. Dr. Zarate 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. HPB has consulted to the Milken Institute. MW is a member of the following advisory boards and gave presentations to the following companies: Bayer AG, Germany; Boehringer Ingelheim, Germany; and Biologische Heilmittel Heel GmbH, Germany. MW has further conducted studies with institutional research support from HEEL and Janssen Pharmaceutical Research for a clinical trial (IIT) on ketamine in patients with MDD, unrelated to this investigation. MW did not receive any financial compensation from the companies mentioned above. IA received speakers honorarium from Lundbeck. IBH is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies. AC reports being currently an employee of the Regeneron Genetics Center, and may own Regeneron stock or stock options. JCS acknowledge to be related with the next companies ALKERMES (Advisory Board), BOEHRINGER Ingelheim (Consultant), COMPASS Pathways (Research Grant), JOHNSON & JOHNSON (Consultant), LIVANOVA (Consultant), RELMADA (Research Grant), SUNOVION (Research Grant),Mind Med (Research Grant). PMP received payment or honoraria for lectures and presentations in educational events for Sandoz, Daiichi Sankyo, Eurofarma, Abbot, Libbs, Instituto Israelita de Pesquisa e Ensino Albert Einstein, Instituto D’Or de Pesquisa e Ensino. All other authors report no biomedical financial interests, disclosures or potential conflicts of interest.

Figures

**Figure 1.**
Cohen’s d map represents significant ROIs without the global covariate and threshold of pFDR < 0.05. From left to right, middle slices of sagittal, axial, and coronal views were used, except for C, where only the sagittal view was used. The figure includes three sections: A) FA and RD for individuals with a lifetime history of suicide attempt versus HC, B) FA for individuals with a lifetime history of suicide attempt versus CLC and C) FA and RD for individuals with recent suicidal ideation versus HC. Abbreviations: CLC= clinical control group ; FA= fractional anisotropy; HC= healthy control group; pFDRR= p value corrected using Benjamini Hochberg correction; RD= radial diffusivity; ROI= region of interest; SA= individuals with a lifetime history of suicide attempt; SI= individuals with recent suicidal ideation.

See this image and copyright information in PMC

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

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

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