【作者】 王向； 刘倩； 樊洁； 高峰； 夏结； 朱熊兆；

【Author】 Xiang Wang;Qian Liu;Jie Fan;Feng Gao;Jie Xia;Xiongzhao Zhu;Medical Psychological Center,the Second Xiangya Hospital,Central South University;Medical Psychological Institute of Central South University;National Clinical Research Center for Mental Disorders;

【机构】 中南大学湘雅二医院医学心理中心； 中南大学医学心理研究所； 国家精神心理疾病临床医学研究中心；

【摘要】 目的:童年创伤(Childhood trauma,CT)已被证明是抑郁症(Major depressive disorder,MDD)的重要风险因素。然而CT在MDD发生发展中的具体作用及其神经机制尚不清楚。本研究的目的是在MDD患者及健康被试(Healthy controls,HC)中,探索童年创伤相关的静息态脑自发活动和功能连接(Functional connectivity,FC)特征,并明确其在CT和抑郁关系间的作用。方法:本研究纳入性别、年龄及言语智商上均匹配的四组被试:有CT的MDD患者(n=91)、无CT的MDD患者(n=32)、有CT的HC(n=33)以及无CT的HC(n=46)。所有被试完成贝克抑郁量表、状态特质焦虑问卷、压力知觉量表评估以及静息态功能磁共振扫描。采用2(CT:有/无)×2(诊断:MDD/HC)析因设计,探索低频振幅(ALFF)值存在CT主效应及CT和诊断交互效应的脑区,并将其作为感兴趣区(ROI)进行基于种子点的全脑FC,探索FC存在CT主效应或CT和诊断交互效应的脑区。对有显著差异脑区的FC值与临床症状之间进行偏相关分析及中介效应检验,来探讨CT影响抑郁的潜在神经机制。以上统计分析均控制人口学变量,在涉及CT的影响时,将压力知觉作为额外的控制变量。结果:ALFF值存在CT主效应的脑区为左侧颞下回(FWE矫正,p<0.05,39体素)。FC分析显示左侧颞下回与双侧楔前叶的FC存在童年创伤与诊断的交互效应(FWE矫正,p<0.05,50体素);简单效应分析表明,CT使得MDD患者左侧颞下回-楔前叶FC减弱,但在HC中,CT则使得该FC增强。偏相关性分析及中介效应检验显示,在MDD中,左侧颞下回-楔前叶FC值与抑郁得分显著相关(r=-0.30,p=0.001),且FC完全中介情感忽视和抑郁水平的关系(β=0.10,95%CI:0.03-0.29);在HC中,左侧颞下回-楔前叶FC值与特质焦虑得分显著相关(r=0.38,p=0.001),FC完全中介性虐待与特质焦虑的关系(β=0.09,95%CI:0.07-1.02)。结论:相比于无CT的被试,有CT的被试左侧颞下回脑自发活动减弱,然而CT相关的左侧颞下回-楔前叶的FC异常改变在MDD患者和HC中的表现不同。左侧颞下回脑自发活动及其与楔前叶功能连接异常改变可能在童年创伤影响抑郁症发生发展的机制中产生重要影响。更多还原

【Abstract】 Purpose: Childhood trauma(CT) has been proven to be a high-risk factor for major depressive disorder(MDD), but the specific role of CT in the occurrence and development of MDD and its neural mechanisms are still unclear. The purpose of this study is to explore the characteristics of resting state brain spontaneous activity and functional connectivity(FC) related to CT in MDD patients and healthy controls(HC), and to clarify its role in the relationship between childhood trauma and depression. Methods: Four age, gender, verbal IQ matched groups of subjects were included in this study: MDD patients with CT(n=91), MDD patients without CT(n=32), HC with CT(n=33), and HC without CT(n=46). All subjects completed clinical assessments including Beck Depression Inventory(BDI), Spielberger State-Trait Anxiety Inventory(STAI), and Perceived Stress Scale(PSS), as well as resting-state functional magnetic resonance scan. 2(CT: yes/no) × 2(MDD/HC) factorial design was used to explore the brain regions of the main effect of CT and/or the effect of MDD diagnosis-by-CT interactions on the low-frequency amplitude(ALFF) value. Then, the regions showed altered ALFF value related to CT were chosen as regions of interest(ROIs) for whole brain FC analysis to explore the brain areas where the main effect of CT or the effect of MDD diagnosis-by-CT interactions on seed-based FC existed. Finally, the partial correlation analyses between altered FC values related to CT and the clinical symptoms were performed, and the mediation tests were further carried out to explore the potential neural mechanism of the effect of childhood trauma on depression. Age, gender, and verbal IQ were controlled in all steps. The recent stress level(PSS) was additionally controlled when investigating the effects involving CT. Results: The left inferior temporal gyrus(left ITG) was detected as the region of the main effect of CT on ALFF value(FWE corrected, p<0.05, voxel size = 39). Thus, left ITG was chosen as the region of interest(ROI) to perform the seed-to voxel FC. For FC based on left ITG seed, there was significant effect of MDD diagnosis-by-CT interactions was observed in bilateral precuneus(FWE corrected, p<0.05, voxel size = 50). Simple effect analysis shows that in MDD patient group, CT weakened the left ITG-precuneus FC, but in HC group, CT could enhance the FC between left ITG and bilateral precuneus. Partial correlation analyses and mediation tests showed that in MDD group, the left ITG-precuneus FC value was significantly correlated with the BDI score(r =-0.30, p = 0.001), and FC completely mediates the relationship between emotional neglect and depression level(β =0.10, 95% CI: 0.03 to 0.29); in HC group, left ITG-precuneus FC value is significantly correlated with trait anxiety(r= 0.38, p = 0.001), FC completely mediates the relationship between sexual abuse and trait anxiety(β = 0.09, 95% CI:0.07 to 1.02). Conclusion: Independent of MDD diagnosis, participants with CT indicated decreased spontaneous brain activity(ALFF) in the left inferior temporal gyrus. However, the effect of CT on altered FCs of the left ITG-precuneus are different in MDD group and HC group. The altered spontaneous activity of the left inferior temporal gyrus and its FC with the precuneus may play an important role in the mechanism of the effect of childhood trauma on depression.更多还原