School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Medical Imaging Department, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Psychol Med. 2019 Nov;49(15):2608-2616. doi: 10.1017/S0033291718003616. Epub 2018 Dec 6.
We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).
We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of 'TNF-α × treatment' in the regions with between-group FC difference.
Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of 'TNF-α × treatment' was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.
These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
我们假设肿瘤坏死因子-α（TNF-α）可能在干扰选择性 5-羟色胺再摄取抑制剂（SSRI）对重度抑郁症（MDD）患者纹状体连接的作用方面发挥作用。
我们通过结合静息态功能磁共振成像（rs-fMRI）和生化分析进行了纵向观察，以确定 MDD 患者纹状体连接的异常，并评估 TNF-α 水平在 SSRI 治疗过程中对这些异常连接的影响。从 25 名 MDD 患者和 35 名健康对照者中采集了 85 次 rs-fMRI 扫描，并且所有患者在 SSRI 治疗前和治疗后均重复了这些扫描。通过将 rs-fMRI 时间序列与纹状体种子（即放置在纹状体中的球形区域）之间的每个体素相关联，计算全脑体素功能连接（FC）。通过 Milliplex 测定法评估血清中 TNF-α 的水平。通过因子分析评估“TNF-α×治疗”在组间 FC 差异区域的交互作用效应。
与对照组相比，在 SSRI 治疗前，MDD 患者的内侧前额叶皮质（MPFC）和双侧中/上颞叶皮质的纹状体 FC 明显更高（p <0.001，未校正）。此外，在 MDD 患者的 MPFC-纹状体 FC 中发现了“TNF-α×治疗”的显著交互作用效应（p = 0.002），并且在调整年龄，性别，头部运动和疾病发作后，该效应仍然存在。
这些发现提供了证据表明，与治疗相关的大脑连接变化取决于 MDD 患者的 TNF-α 水平，并且 MPFC-纹状体连接可能是大脑中的重要靶标。
