Mediation on the Association Between Stressful Life Events and Depression by Abnormal White Matter Microstructures

BACKGROUND: Stressful life events (SLEs) are an important causal factor in depression; however, the mechanism by which SLEs cause depression remains unclear. Recent studies suggested that white matter (WM) microstructures might be a potential mediator between SLEs and depression. Hence, we aimed to investigate the concrete correspondence among them using mediation effect models. METHODS: In participants (N = 194) with SLEs experience prospectively recruited from six residential communities, WM microstructures were detected with diffusion tensor imaging. The interrelationship among SLEs, WM microstructures, and depression was explored with multiple linear regression models and logistic regression models. Furthermore, the influence of WM microstructures on the association between SLEs and depression was tested with mediation effect models. RESULTS: Successfully established mediation effect models showed the specific influence of fractional anisotropy of the corpus callosum and left uncinate fasciculus on the association between SLEs and depression onset (ab path = 0.032; ab path = 0.026, respectively) and between SLEs and depressive severity (ab path = 0.052; ab path = 0.067, respectively). In addition, significant total mediation effects on the association between SLEs and depression onset (ab path = 0.031) and severity (ab path = 0.075) through fractional anisotropy of the corpus callosum and left uncinate fasciculus were noted. CONCLUSIONS: WM microstructure alterations impose a substantial mediation effect on the association between SLEs and depression, which suggest that changes in WM microstructure integrity might increase the risk of depression onset and unfavorable disease courses induced by the SLEs.