【摘要】 目的：重度抑郁障碍（major depressive disorder,MDD）是一种常见的情感障碍，其病因复杂，病理机制仍未阐明。伏隔核（nucleus accumbens,NAc）在奖赏处理、动机调节和情绪整合等生理过程中扮演核心角色。神经影像学研究提示NAc的结构和功能异常在MDD的发病机制中起关键作用。然而，目前关于MDD患者NAc的结构-功能耦合（structure-function coupling,SFC）变化特征尚未阐明。本研究旨在通过结合功能磁共振成像（functional magnetic resonance imaging,fMRI）和弥散张量成像（diffusion tensor imaging,DTI）技术，系统探索MDD患者NAc的异常功能连接（functional connectivity,FC）及SFC。方法：采用病例-对照研究设计，纳入符合MDD当前发作诊断标准及17项汉密尔顿抑郁量表（17-item Hamilton Rating Scale for Depression,HAMD-17）评分≥17的MDD患者（MDD组），并设立与之在性别、年龄和受教育时间匹配的健康对照（healthy controls,HCs）组。所有研究对象均由3.0T MR系统采集高分辨率T₁结构像、静息态f MRI和DTI数据。fMRI数据采用SPM12（Statistical Parametric Mapping 12）和DPARSF（Data Processing Assistant for Resting-State fMRI）软件进行预处理，DTI数据采用FSL（FMRIB Software Library）进行预处理。基于脑网络组图谱将大脑灰质分割成246个脑区，分别计算双侧NAc与全脑的FC值和基于概率纤维追踪的结构连接强度（strength of structural connectivity,sSC）值，并采用区域水平Spearman相关方法计算双侧NAc的SFC值（sSC值与FC值之间的Spearman秩相关系数ρ）。建立以FC值为因变量，以年龄、性别、受教育时间及头动参数为自变量的多元线性回归模型，采用最小二乘法进行拟合，并提取回归残差作为校正后的FC值。采用独立样本t检验比较MDD组和HCs组之间校正后的FC值并对检验结果进行错误发现率（false discovery rate,FDR）校正，显著性水平设定为P<0.1。采用协方差分析比较SFC值在2组间的差异，模型中纳入年龄、性别及受教育时间作为协变量。显著性水平设定为P<0.05。将MDD组与HCs组相比差异存在统计学意义的FC值、双侧NAc的SFC值与其HAMD-17总分进行Spearman相关分析。结果：MDD组和HCs组在性别（χ²=0.792,P=0.373）、年龄（t=-0.930,P=0.292）和受教育时间（t=0.003,P=0.059）方面的差异均无统计学意义。与HCs组比较，MDD组BG.L.3（左侧NAc）-IPL.R.4（右侧顶下小叶）、BG.R.3（右侧NAc）-IPL.R.4、BG.R.3-Tha.R.8（右侧外侧前额叶丘脑）、BG.R.3-MFG.R.4（右侧额中回）之间的FC值显著升高（经FDR校正后，P<0.1）。MDD组双侧NAc的SFC值均显著低于HCs组（左侧：F=11.768,P=0.001；右侧：F=4.386,P=0.047）。Spearman相关分析结果显示：MDD组与HCs组相比差异存在统计学意义的FC值、双侧NAc的SFC值与其HAMD-17总分之间均无显著相关性（均P>0.05）。结论：MDD患者NAc的FC增强，且主要集中在NAc与顶下小叶、额中回等认知相关脑区之间，这为奖赏环路与认知调控脑区之间的失衡提供了证据。同时，MDD患者双侧NAc的SFC显著减弱，反映了MDD患者双侧NAc结构与功能的协同整合水平受损。本研究结果为NAc参与MDD的病理机制提供了神经影像学证据。更多还原

【Abstract】 Objective: Major depressive disorder（MDD） is a common affective disorder with complex etiologies and largely unclear pathophysiological mechanisms. The nucleus accumbens（NAc） plays a central role in reward processing, motivational regulation, and emotional integration. Neuroimaging studies suggest that structural and functional abnormalities of the NAc are key contributors to the pathogenesis of MDD. However, the alterations in structure-function coupling（SFC） of the NAc in MDD remain poorly understood. This study aims to systematically investigate abnormal functional connectivity（FC） and SFC of the NAc in patients with MDD by integrating functional magnetic resonance imaging（fMRI） and diffusion tensor imaging（DTI） techniques.Methods: A case-control design was adopted. Patients who met diagnostic criteria for a current depressive episode of MDD and had a 17-item Hamilton Rating Scale for Depression（HAMD-17） total score ≥17 were enrolled as the MDD group, while age-, sex-, and education-matched healthy controls（HCs） were included as the HC group. All participants underwent high-resolution T₁-weighted structural imaging, resting-state fMRI, and DTI scanning using a 3.0T MR system. fMRI data preprocessing was performed using SPM12（Statistical Parametric Mapping 12） and DPARSF（Data Processing Assistant for Resting-State fMRI）, while DTI preprocessing was conducted using FSL（FMRIB Software Library）. Based on the Brainnetome Atlas, the cerebral cortex was parcellated into 246 regions. FC values between bilateral NAc and the whole brain and the strength of structural connectivity（sSC） derived from probabilistic tractography were calculated. SFC values of bilateral NAc were computed using region-wise Spearman correlations between sSC and FC（ρ）. A multiple linear regression model was constructed using FC as the dependent variable and age, gender, years of education, and head motion parameters as covariates, and corrected FC values were extracted from the regression residuals. Group differences in corrected FC values were assessed using independent-sample t-tests with false discovery rate（FDR） correction at a significance level of P<0.1. Analysis of covariance was used to compare SFC values between groups, controlling for age, gender, and years of education（a significance level of P<0.05）. FC values showing significant intergroup differences and SFC values of bilateral NAc were correlated with HAMD-17 total scores using Spearman correlation analysis.Results: There were no significant differences between the MDD and the HC groups in gender（χ2=0.792, P=0.373）, age（t=-0.930, P=0.292）, or years of education（t=0.003, P=0.059）. Compared with HCs, patients with MDD exhibited significantly increased FC in the following connections: BG.L.3（left NAc）-IPL.R.4（right inferior parietal lobule）, BG.R.3（right NAc）-IPL. R. 4, BG. R. 3-Tha. R. 8（right lateral prefrontal thalamus）, and BG. R. 3-MFG. R. 4（right middle frontal gyrus）（all FDR-corrected P<0.1）. The SFC values of bilateral NAc were significantly reduced in the MDD group compared with the HC group（left: F=11.768, P=0.001; right: F=4.386, P=0.047）. Spearman correlation analyses showed no significant associations between altered FC or bilateral NAc SFC values and HAMD-17 total scores in the MDD group（all P>0.05）.Conclusion: Patients with MDD exhibit enhanced NAc FC, predominantly between the NAc and cognition-related regions such as the inferior parietal lobule and middle frontal gyrus, suggesting imbalance between the reward circuit and cognitive regulatory networks. Moreover, the significantly reduced SFC of bilateral NAc indicated impaired structuralfunctional integration in MDD. These findings provide potential neuroimaging evidence supporting the involvement of the NAc in the pathophysiological mechanisms of MDD.更多还原