Interleukin-6-white matter network differences explained the susceptibility to depression after stressful life events

Background: Stressful life events (SLEs) are well-established proximal predictors of the onset of depression. However, the fundamental causes of interindividual differences in depression outcomes are poorly understood. This study addressed this depression susceptibility mechanism using a well-powered sample of adults living in China. Methods: Healthy participants with SLEs (n = 185; mean = 47.51 years, 49.73% female), drawn from a longi-tudinal study on the development of depression, underwent diffusion tensor imaging, interleukin-6 (IL-6) level measurement, and trimonthly standardized clinical and scale evaluations within a two-year period. Results: Receiver operating characteristic analyses indicated that reduced feeder connection and HIP.R nodal efficiency improved the predictive accuracy of post-SLEs depression (ORfeeder = 0.623, AUC = 0.869, P < 0.001; ORHIP = 0.459, AUC = 0.855, P < 0.001). The successfully established path analysis model confirmed the significant partial effect of SLEs-IL-6-white matter (WM) network differences-depression (onset and severity) (x2/8 = 1.453, goodness-of-fit [GFI] = 0.935, standard root-mean-square error of approximation [SRMR] = 0.024). Females, individuals with lower exercise frequency (EF) or annual household income (AHI) were more likely to have higher IL-6 level after SLEs (beta(int-female*SLEs) =-0.420, P < 0.001; beta(int-exercise*SLEs) =-0.412, P < 0.001; beta(int-income*SLEs) =-0.302, P = 0.005). Limitations: The sample size was restricted due to the limited incidence rate and prospective follow-up design. Conclusions: Our results suggested that among healthy adults after SLEs, those who exhibited abnormal IL-6-WM differences were susceptible to developing depression. Females, lower AHI or EF might account for an increased risk of developing these abnormal IL-6-WM differences.

Automated summary

This study examined the impact of stressful life events (SLEs) on the susceptibility to depression. The results showed that individuals with abnormal IL-6-white matter differences were more likely to develop depression after SLEs. Females, lower annual household income, and lower exercise frequency were factors associated with an increased risk of developing these abnormal differences.