Structural and functional neural correlates of developmental and psychosocial risk factors for lifetime suicidal ideation: a transdiagnostic neuroimaging study

Background

Suicidal ideation (SI) is a major public health concern, yet its neurobiological underpinnings remain poorly understood. While developmental and psychosocial factors such as childhood maltreatment, personality, and cognitive emotion regulation have been associated with risk [1], the neural pathways linking these factors to SI remain unexplored. Large-scale ENIGMA-STB analyses found no significant associations between SI and cortical or subcortical measures [2]. This study examined structural and functional neural correlates of developmental and psychosocial risk factors for SI in a transdiagnostic sample.

Methods

Data were obtained from the Transdiagnostic Connectome Project [3], an openly available multi-site dataset (OpenNeuro ds005237). The final sample comprised 170 participants (89 lifetime SI, 81 without; 106 patients, 64 controls; mean age 32.9; 60% female). Thirty-five measures from nine instruments spanning personality, cognitive regulation, childhood trauma, temperament, impulsivity, rumination, social support, and attachment were compared between SI groups. Associations between SI-related measures and 30 a priori grey matter volumes were examined using regression, controlling for age, diagnostic group, sex, site, and intracranial volume. Direct SI group comparisons were tested via ROI analysis and whole-brain voxel-based morphometry. Based on structural findings, a medial temporal lobe (MTL) seed set comprising bilateral anterior/posterior hippocampus and medial/lateral amygdala was selected for seed-based resting-state FC analysis. FC between MTL seeds and 426 non-MTL targets was compared between SI groups, controlling for age, group, sex, site, and mean framewise displacement. The FC finding was additionally examined across three C-SSRS severity levels: no SI (n = 81), ideation only (n = 65), and plan or attempt (n = 24). All analyses were FDR-corrected.

Results

Twenty of 35 measures were significantly associated with SI after FDR correction, spanning childhood trauma, personality, cognitive regulation, temperament, impulsivity, and attachment. Self-blame was negatively associated with right (β = −0.024, pFDR = .034) and left hippocampal volume (β = −0.023, pFDR = .034), and openness positively with left amygdala volume (β = +0.003, pFDR = .031). No direct structural differences were observed between SI groups. Seed-based FC revealed increased right amygdala–dorsal attention network (superior parietal lobule) connectivity in the SI group (t = 4.56, pFDR = .034). Supplementary whole-brain, network-level, and within-network analyses yielded no significant differences. Amygdala–dorsal attention connectivity increased progressively across SI severity groups (linear trend p < .001), though ideation-only and plan/attempt groups did not differ significantly.

Conclusions

Self-blame and openness are associated with medial temporal lobe structure, yet SI groups show no direct volumetric differences. Resting-state FC analysis revealed increased amygdala–dorsal attention coupling in the SI group, with a progressive increase across severity levels. Altered amygdala connectivity has been reported in prior studies of suicidal thoughts and behaviours, with varying target regions across clinical samples [4], and altered dorsal attention network connectivity has been observed in suicidal depression [5]. The present study extends these findings by identifying a specific amygdala–parietal pathway in a transdiagnostic sample. The identification of a cortical target within the dorsal attention network may inform future research on neuromodulation-based approaches.

References

1. O’Connor, R. C., & Nock, M. K. (2014). The psychology of suicidal behaviour. The Lancet Psychiatry, 1(1), 73-85.
2. Van Velzen, L. S., Dauvermann, M. R., Colic, L., Villa, L. M., Savage, H. S., Toenders, Y. J., … & Schmaal, L. (2022). Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium. Molecular psychiatry, 27(11), 4550-4560.
3. Chopra, S., Cocuzza, C. V., Lawhead, C., Ricard, J. A., Labache, L., Patrick, L. M., … & Holmes, A. J. (2025). The Transdiagnostic Connectome Project: an open dataset for studying brain-behavior relationships in psychiatry. Scientific Data, 12(1), 923.
4. Schmaal, L., van Harmelen, A. L., Chatzi, V., Lippard, E. T., Toenders, Y. J., Averill, L. A., … & Blumberg, H. P. (2020). Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies. Molecular psychiatry, 25(2), 408-427.
5. Lee, S., Lee, S. M., Kang, W. S., Jahng, G. H., Ryu, C. W., & Park, J. K. (2019). Altered resting-state functional connectivity in depressive disorder patients with suicidal attempts. Neuroscience Letters, 696, 174-178.