Brain structural changes and their role in increasing depression risk following spinal cord injury: evidence from the UK biobank

Spinal cord injury (SCI) markedly increases the risk of depression, affecting 16-30% of patients and contributing to elevated mortality. In this study, we used UK Biobank data to explore the relationship between SCI and depression, with a particular focus on structural brain changes as potential mediators. Cox regression models, adjusted for sociodemographic and lifestyle factors, demonstrated that participants with SCI had a significantly higher incidence of depression than those without, with the effect more pronounced in women. Genetic predisposition further intensified the risk, with SCI associated with a 2.1-fold, 2.7-fold, and 3.6-fold increase in depression risk at low, medium, and high polygenic risk score levels, respectively. Neuroimaging analysis revealed cortical thinning in frontal areas, ventricular enlargement, and thalamic signal intensity changes, while mediation analysis indicated that brain structural alterations accounted for 6-9% of depression risk after SCI, particularly involving the right S. interm. prim. Jensen, left lateral ventricle, and thalamus. These findings underscore the complex interplay of structural brain changes, sex differences, and genetic susceptibility in mediating depression risk following SCI, and suggest potential targets for therapeutic intervention.