The Analysis On Mediation Effect Of Whiter Matter Micro-strutures On Stressful Life Events And Depression Based On Diffusion Tensor Imaging

Objective1.To explore the effects of stressful life events(SLEs)on the brain white matter micro-structures by using the diffusion tensor imaging(DTI)technique,and to find a better indicator that could reflect the damage degree of white matter micro-structures caused by SLEs.2.To investigate the characteristic changes of white matter micro-structures in depression patients with SLEs experience based on DTI technique.In addition,we could further explore whether the white matter micro-structures mediated the influence of SLEs on depression though analyzing the relationships among SLEs,white matter micro-structures and depression,which is helpful to reveal the specific corresponding relationship between SLEs and depression.Methods1.The 46 healthy participants with SLEs experience(SLEs group)and 46age-and sex-matched healthy participants without SLEs experience(non-SLEs group)underwent DTI-MRI scanning,and analysis was performed using the tract-based spatial statistics(TBSS).The presence and level of SLEs that occurred over the previous 12 months were assessed using the Holmes and Rahe Social Readjustment Rating Scale(SRRS).The white matter micro-structures between the SLEs and the non-SLEs groups were compared with two-sample t-test.The correlation between abnormal white matter micro-structures and SLEs were analyzed by Pearson correlation.2.A total of 300 participants with SLEs experience,as a high-risk group for depression,were prospectively recruited from the community for a 2-year longitudinal study,and were followed every 3 months.The white matter micro-structures of all participants were detected with DTI,the SLEs impact were evaluated using the SRRS,the presence of depression mental state was determined using the Structured Clinical Interview of the DSM-IV(SCID),and the depressive severity was evaluated using 17-item Hamilton Depression Rating Scale(HDRS).At the end of follow-up,the participants were divided into depression and non-depression groups based on the presence or absence of depression,and the white matter micro-structures of the two groups were compared using TBSS.The relationship with each other among SLEs,WM micro-structures and depression were respectively explored with multiple linear regression models and logistic regression models.Furthermore,the influence of white matter micro-structures on the association between SLEs and depression was tested with the mediation effect models.Results1.Compared with the non-SLEs group,the SLEs group showed significantly decreased fractional anisotropy(FA)values in the right superior corona radiata,the corpus callosum,the right cingulate and left uncinate fasciculus and significantly increased mean diffusivity(MD)values in the corpus callosum and bilateral anterior corona radiata as well as significantly increased radial diffusivity(RD)values in the corpus callosum,the right cingulate and right posterior thalamic radiation.2.After controlling for age and sex covariates,there were significantly negative correlation between the FA values of right superior corona radiata,the corpus callosum,the right cingulate and left uncinate fasciculus and SRRS sum scores in the SLEs group(r =-0.503,P = 0.001;r =-0.638,P = 0.001;r =-0.607,P = 0.001;r =-0.453,P = 0.001),while there were significantly positive correlation between MD values of the corpus callosum and bilateral anterior corona radiata(r = 0.575,P =0.001;r = 0.398,P = 0.006;r = 0.432,P = 0.003)as well as RD values of the corpus callosum,the right cingulate and right posterior thalamic radiation(r = 0.565,P =0.001;r = 0.342,P = 0.020;r = 0.320,P = 0.030)and SRRS sum scores.Additionally,compared with MD values and RD values,FA values in differential brain region(corpus callosum and right cingulate)had a higher absolute value ofcorrelation coefficient with SRRS sum scores.3.During the 2-year longitudinal study,30(15.0%)of the 194 participants with SLEs experience eventually were diagnosed with depression.4.There were significant differences in SRRS sum scores between depression group and non-depression group after being controlled for age,sex,annual income level and HDRS scores(baseline).Moreover,the logistic regression model revealed that the SLEs effectively predicted depression onset(OR = 1.037,95% CI: 1.013-1.063;P = 0.003).Furthermore,the multiple linear regression model showed a significantly positive correlation between SRRS sum scores and HDRS scores(follow-up)(β = 0.366,P = 0.024)in depression,controlling these related covariates.5.Compared with the non-depression group,the depression group showed significant FA values differences in the corpus callosum and left uncinate fasciculus.6.Multiple regression models showed there were significantly negative correlations between SRRS sum scores and FA values of the corpus callosum and left uncinate fasciculus in the depression group(β =-0.383,P = 0.016;β =-0.451,P =0.001),and the significant correlations also were found in all participants(β =-0.538,P = 0.001;β =-0.502,P = 0.001).7.Logistic regression models showed that effective predictions of depression onset based on FA values of the corpus callosum and the left uncinate fasciculus(OR= 0.345,95% CI: 0.240-0.530,P = 0.001;OR = 0.322,95% CI: 0.185-0.529,P =0.001)could respectively be achieved.Moreover,FA values of the corpus callosum and left uncinate fasciculus were respectively significantly negatively correlated with depressive severity in the depression(β =-0.593,P = 0.001;β =-0.636,P = 0.001).8.Mediation effect models showed that the FA values of corpus callosum significantly mediated the relationship between SLEs and depression onset and depressive severity,respectively(ab path = 0.032,SE = 0.009,95% CI: 0.018-0.054;ab path = 0.052,SE = 0.029,95% CI: 0.006-0.116).A similar mediation effect also was found in the FA values of left uncinate fasciculus(ab path = 0.026,SE = 0.008,95% CI: 0.009-0.040;ab path = 0.067,SE = 0.031,95% CI: 0.018-0.135).Furthermore,in the combined mediation model with FA values of the corpus callosum and left uncinate fasciculus as the mediator variables,there were significantly total mediation effects on the association between SLEs and depression onset and severity through FA values of the corpus callosum and left uncinate fasciculus,respectively(ab path = 0.031,SE = 0.010,95% CI: 0.016-0.054;ab path = 0.075,SE = 0.034,95% CI: 0.022-0.154).Conclusion1.The SLEs experience adversely affected brain white matter micro-structures.In addition,FA values,as the most common diffusion characteristic in DTI technology,could be a better neurobiological indicator to reflect the influence of SLEs on the integrity of white matter micro-structures.2.Depression,SLEs and white matter micro-structures were closely related with each other.Differential white matter micro-structures(FA values of the corpus callosum and left uncinate fasciculus)could significantly mediate the influence of SLEs on the depression onset and severity.