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

Van Velzen, L. S.; Colic, L.; Ceja, Z.; Dauvermann, M. R.; Villa, L. M.; Savage, H. S.; Toenders, Y. J.; Dehestani, N.; Zhu, A. H.; Campos, A. I.; Salminen, L. E.; Alda, M.; Agartz, I.; Alexander, N.; Ayesa-Arriola, R.; Ballard, E. D.; Banaj, N.; Barkhau, C.; Basgoze, Z.; Bauer, J.; Benedetti, F.; Berger, K.; Besteher, B.; Brosch, K.; Canal-Rivero, M.; Cervenka, S.; Colle, R.; Connolly, C. G.; Corruble, E.; Courtet, P.; Couvy-Duchesne, B.; Crespo-Facorro, B.; Cullen, K. R.; Dannlowski, U.; Deverdun, J.; Diaz-Zuluaga, A. M.; Dietze, L. M. F.; Evans, J. W.; Fani, N.; Flinkenflugel, K.; Friedman, N. P.; Gotlib, I. H.; Groenewold, N. A.; Grotegerd, D.; Hajek, T.; Hatoum, A. S.; Hermesdorf, M.; Hickie, I. B.; Hirano, Y.; T. C., Ho; Ikemizu, Y.; Iorfino, F.; Ipser, J. C.; Isobe, Y.; Jackowski, A. P.; Jollant, F.; Kircher, T.; Klug, M.; Koopowitz, S. -M.; Kraus, A.; Krug, A.; Le Bars, E.; Leehr, E. J.; Li, M.; Lippard, E. T. C.; Lopez-Jaramillo, C.; Maximov, I. I.; Mcintosh, A. M.; Mclaughlin, K. A.; Mcwhinney, S. R.; Meinert, S.; Melloni, E.; Mitchell, P. B.; Mwangi, B.; Nenadic, I.; Nerland, S.; Olie, E.; Ortiz-Garcia de la Foz, V.; Pan, P. M.; Pereira, F.; Piras, F.; Piras, F.; Poletti, S.; Reineberg, A. E.; Roberts, G.; Romero-Garcia, R.; Sacchet, M. D.; Salum, G. A.; Sandu, A. -L.; Sellgren, C. M.; Shimizu, E.; Smolker, H. R.; Soares, J. C.; Steele, J. D.; Stein, F.; Stein, D. J.; Straube, B.; Teutenberg, L.; Thomas-Odenthal, F.; Usemann, P.; Valabregue, R.; Valencia-Echeverry, J.; Wagner, G.; Waiter, G.; Walter, M.; Whalley, H. C.; M. -J., Wu; Yang, T. T.; Zarate, C. A.; Zugman, A.; Zunta-Soares, G. B.; Van Heeringen, K.; Van Rooij, S. J. H.; Van Der Wee, N.; Van Der Werff, S.; Thompson, P. M.; Blumberg, H. P.; Van Harmelen, A. -L.; Renteria, M. E.; Jahanshad, N.; Van Rooij, S. J. H.; Van Heeringen, K.; De La Foz, V. O. -G.; Le Bars, E.; Van Velzen, L. S.; Schmaal, L.

doi:10.1038/s41398-025-03602-1

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.

Transdiagnostic alterations in white matter microstructure associated with suicidal thoughts and behaviours in the ENIGMA Suicidal Thoughts and Behaviours consortium / Van Velzen, L. S.; Colic, L.; Ceja, Z.; Dauvermann, M. R.; Villa, L. M.; Savage, H. S.; Toenders, Y. J.; Dehestani, N.; Zhu, A. H.; Campos, A. I.; Salminen, L. E.; Alda, M.; Agartz, I.; Alexander, N.; Ayesa-Arriola, R.; Ballard, E. D.; Banaj, N.; Barkhau, C.; Basgoze, Z.; Bauer, J.; Benedetti, F.; Berger, K.; Besteher, B.; Brosch, K.; Canal-Rivero, M.; Cervenka, S.; Colle, R.; Connolly, C. G.; Corruble, E.; Courtet, P.; Couvy-Duchesne, B.; Crespo-Facorro, B.; Cullen, K. R.; Dannlowski, U.; Deverdun, J.; Diaz-Zuluaga, A. M.; Dietze, L. M. F.; Evans, J. W.; Fani, N.; Flinkenflugel, K.; Friedman, N. P.; Gotlib, I. H.; Groenewold, N. A.; Grotegerd, D.; Hajek, T.; Hatoum, A. S.; Hermesdorf, M.; Hickie, I. B.; Hirano, Y.; Ho, T. C.; Ikemizu, Y.; Iorfino, F.; Ipser, J. C.; Isobe, Y.; Jackowski, A. P.; Jollant, F.; Kircher, T.; Klug, M.; Koopowitz, S. -M.; Kraus, A.; Krug, A.; Le Bars, E.; Leehr, E. J.; Li, M.; Lippard, E. T. C.; Lopez-Jaramillo, C.; Maximov, I. I.; Mcintosh, A. M.; Mclaughlin, K. A.; Mcwhinney, S. R.; Meinert, S.; Melloni, E.; Mitchell, P. B.; Mwangi, B.; Nenadic, I.; Nerland, S.; Olie, E.; Ortiz-Garcia de la Foz, V.; Pan, P. M.; Pereira, F.; Piras, F.; Piras, F.; Poletti, S.; Reineberg, A. E.; Roberts, G.; Romero-Garcia, R.; Sacchet, M. D.; Salum, G. A.; Sandu, A. -L.; Sellgren, C. M.; Shimizu, E.; Smolker, H. R.; Soares, J. C.; Steele, J. D.; Stein, F.; Stein, D. J.; Straube, B.; Teutenberg, L.; Thomas-Odenthal, F.; Usemann, P.; Valabregue, R.; Valencia-Echeverry, J.; Wagner, G.; Waiter, G.; Walter, M.; Whalley, H. C.; Wu, M. -J.; Yang, T. T.; Zarate, C. A.; Zugman, A.; Zunta-Soares, G. B.; Van Heeringen, K.; Van Rooij, S. J. H.; Van Der Wee, N.; Van Der Werff, S.; Thompson, P. M.; Blumberg, H. P.; Van Harmelen, A. -L.; Renteria, M. E.; Jahanshad, N.; Van Rooij, S. J. H.; Van Heeringen, K.; De La Foz, V. O. -G.; Le Bars, E.; Van Velzen, L. S.; Schmaal, L.. - In: TRANSLATIONAL PSYCHIATRY. - ISSN 2158-3188. - 15:1(2025). [10.1038/s41398-025-03602-1]