Transdiagnostic alterations in white matter microstructure associated with suicidal thoughts and behaviours in the ENIGMA Suicidal Thoughts and Behaviours consortium
Authors: van Velzen Laura S. , Colic Lejla , Ceja Zuriel , Dauvermann Maria R. , Villa Luca M. , Savage Hannah S. , Toenders Yara J. , Dehestani Niousha , Zhu Alyssa H. , Campos Adrian I. , Salminen Lauren E. , Agartz Ingrid , Alexander Nina , Ayesa-Arriola Rosa , Ballard Elizabeth D. , Banaj Nerisa , Barkhau Carlotta , Başgöze Zeynep , Bauer Jochen , Benedetti Francesco , Berger Klaus , Besteher Bianca , Brosch Katharina , Canal-Rivero Manuel , Cervenka Simon , Colle Romain , Connolly Colm G. , Corruble Emmanuelle , Courtet Philippe , Couvy-Duchesne Baptiste , Crespo-Facorro Benedicto , Cullen Kathryn R , Dannlowski Udo , Deverdun Jeremy , Diaz-Zuluaga Ana M. , Dietze Lorielle M.F. , Evans Jennifer W , Fani Negar , Flinkenflügel Kira , Friedman Naomi P. , Gotlib Ian H. , Groenewold Nynke A. , Grotegerd Dominik , Hajek Tomas , Hatoum Alexander S. , Hermesdorf Marco , Hickie Ian B. , Hirano Yoshiyuki , Ho Tiffany C. , Ikemizu Yuki , Iorfino Frank , Ipser Jonathan C. , Isobe Yuko , Jackowski Andrea P. , Jollant Fabrice , Kircher Tilo , Klug Melissa , Koopowitz Sheri-Michelle , Kraus Anna , Krug Axel , Bars Emmanuelle Le , Leehr Elisabeth J. , Li Meng , Lippard Elizabeth T.C. , Lopez-Jaramillo Carlos , Maximov Ivan I. , McIntosh Andrew M. , McLaughlin Katie A. , McWhinney Sean R. , Meinert Susanne , Melloni Elisa , Mitchell Philip B. , Mwangi Benson , Nenadić Igor , Nerland Stener , Olie Emilie , Ortiz-García de la Foz Victor , Pan Pedro M. , Pereira Fabricio , Piras Fabrizio , Piras Federica , Poletti Sara , Reineberg Andrew E. , Roberts Gloria , Romero-García Rafael , Sacchet Matthew D. , Salum Giovanni A. , Sandu Anca-Larisa , Sellgren Carl M. , Shimizu Eiji , Smolker Harry R. , Soares Jair C. , Spalletta Gianfranco , Steele J. Douglas , Stein Frederike , Stein Dan J. , Straube Benjamin , Teutenberg Lea , Thomas-Odenthal Florian , Usemann Paula , Valabregue Romain , Valencia-Echeverry Johanna , Wagner Gerd , Waiter Gordon , Walter Martin , Whalley Heather C. , Wu Mon-Ju , Yang Tony T. , Zarate Carlos A. , Zugman Andre , Zunta-Soares Giovana B. , van Heeringen Kees , van Rooij Sanne J.H. , van der Wee Nic , van der Werff Steven , Thompson Paul M. , Blumberg Hilary P. , van Harmelen Anne-Laura , Rentería Miguel E. , Jahanshad Neda ,   ENIGMA Suicidal Thoughts and Behaviours Consortium, Schmaal Lianne 
Published: November 2024

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’sd< 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.