Zhou Huan, Li Hailong, Liu Shiyu, Cao Lingxiao, Chai Shuangwei, Gao Yingxue, Liang Kaili, Tang Mengyue, Zhang Lianqing, Wang Yidan, Hu Xinyue, Qiu Changjian, Gong Qiyong, Huang Xiaoqi
Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Functional and Molecular lmaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Mental Health Center, West China Hospital of Sichuan University, Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, Sichuan, China.
J Psychiatr Res. 2025 Feb;182:430-437. doi: 10.1016/j.jpsychires.2025.01.047. Epub 2025 Jan 24.
Generalized anxiety disorder (GAD) is a prevalent anxiety disorder often comorbid with major depressive disorder (MDD). Previous neuroimaging studies have shown that white matter (WM) microstructural alterations are critical for efficient communication between brain regions, and play an important role in the pathology of GAD. However, the exact profile of WM abnormalities in GAD with and without comorbid MDD remain unclear. This study aimed to uncover them using a novel global probabilistic tractography technology named Tracts Constrained by Underlying Anatomy (TRACULA), and to assess the correlations between fascicle integrity and symptom severity.
We recruited 20 pure GAD (p-GAD) patients, 14 GAD comorbid with MDD (GAD + MDD) patients, and 41 age- and sex-matched healthy controls (HCs). All participants underwent T1 magnetic resonance imaging and diffusion tensor imaging. For each subject, 42 WM fiber bundles of the whole brain were successfully tracked and calculated with five metrics including volume, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Group comparison were firstly performed between the whole GAD patients and HCs. Then, we compared the differences among the three groups (the p-GAD, GAD + MDD patients and HCs) using the one-way ANCOVA and post hoc analysis with the Bonferroni correction. Furthermore, correlations between abnormal WM metrics and clinical symptom severity were examined using partial correlations analyses among patients.
Compare to HCs, both p-GAD and GAD + MDD patients exhibited decreased FA values in left superior longitudinal fasciculus (SLF) II, and right dorsal of cingulum bundle (CBD); Moreover, GAD + MDD patients showed decreased FA, increased MD and RD values in the central and temporal section of the body of the corpus callosum (CC-BODY), right SLF I and II compared to HCs. Within the GAD + MDD group, GAD-7 scores were negatively correlated with FA values (r = -0.75, p = 0.008) and positively correlated with RD values (r = 0.7, p = 0.017) in the right CBD.
This study identified both shared and distinctive changes in GAD patients with and without MDD. The shared WM disruption in the p-GAD and GAD + MDD groups located in the left SLF and right CBD, while only GAD + MDD patients showed distinctive changes in the central and temporal sections of the CC-BODY and right SLF. Current study gave a comprehensive characterization of WM abnormalities among these patients, and highlighted TRACULA's value in identifying critical WM changes.
广泛性焦虑障碍（GAD）是一种常见的焦虑障碍，常与重度抑郁症（MDD）共病。以往的神经影像学研究表明，白质（WM）微观结构改变对于脑区之间的有效沟通至关重要，并且在GAD的病理过程中起重要作用。然而，伴有和不伴有共病MDD的GAD患者中WM异常的确切情况仍不清楚。本研究旨在使用一种名为“基于潜在解剖结构约束的纤维束成像”（TRACULA）的新型全局概率纤维束成像技术来揭示这些情况，并评估纤维束完整性与症状严重程度之间的相关性。
我们招募了20名单纯GAD（p-GAD）患者、14名合并MDD的GAD（GAD + MDD）患者以及41名年龄和性别匹配的健康对照者（HCs）。所有参与者均接受了T1磁共振成像和扩散张量成像。对于每个受试者，成功追踪并计算了全脑42条WM纤维束，并使用包括体积、分数各向异性（FA）、平均扩散率（MD）、径向扩散率（RD）和轴向扩散率（AD）在内的五个指标进行分析。首先在所有GAD患者和HCs之间进行组间比较。然后，我们使用单因素协方差分析和经Bonferroni校正的事后分析比较了三组（p-GAD、GAD + MDD患者和HCs）之间的差异。此外，使用患者之间的偏相关分析检查了异常WM指标与临床症状严重程度之间的相关性。
与HCs相比，p-GAD和GAD + MDD患者左侧上纵束（SLF）II和右侧扣带束（CBD）背侧的FA值均降低；此外，与HCs相比，GAD + MDD患者胼胝体体部（CC-BODY）中央和颞部、右侧SLF I和II的FA值降低，MD和RD值升高。在GAD + MDD组中，右侧CBD的GAD-7评分与FA值呈负相关（r = -0.75，p = 0.008）且与RD值呈正相关（r = 0.7，p = 0.017）。
本研究确定了伴有和不伴有MDD的GAD患者中共同的和独特的变化。p-GAD和GAD + MDD组中共同的WM破坏位于左侧SLF和右侧CBD，而只有GAD + MDD患者在CC-BODY中央和颞部以及右侧SLF显示出独特的变化。当前研究全面描述了这些患者中WM异常情况，并突出了TRACULA在识别关键WM变化方面的价值。
