经皮耳甲迷走神经刺激对难治性抑郁症的即刻脑效应研究

Instant Brain Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Treatment-Resistant Depression

目的 观察经皮耳甲迷走神经刺激(ta VNS)治疗难治性抑郁症(TRD)的即刻脑功能调制效应。资料与方法 选择2018年9月—2020年1月纳入包括中国中医科学院广安门医院、宣武医院、清华大学玉泉医院就诊的TRD患者(n=34)及同期在网上招募的健康志愿者(对照组,n=34)进行前瞻性研究。评估每位受试者的汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)、抑郁自评量表(SDS)、焦虑自评量表(SAS)、冗思反应量表(RRS),并于即刻刺激前后(30 min)采集受试者的静息态功能磁共振成像数据。采用度中心度(DC)方法,比较两组治疗前后的DC特征,进一步提取差异脑区的DC值,分析DC差值(刺激后-刺激前)与HAMD-17、HAMA、SDS、SAS、RRS评分的相关性。结果 与对照组比较,TRD组在左侧海马旁回/杏仁核/伏隔核、双侧背外侧前额叶(左侧额中回、右侧额中回/额上回)的DC值较高、左侧枕中回/枕上回DC较低,两组刺激前后的差值在前扣带回膝部/眶回内侧部存在差异,以上差异脑区均经高斯随机场校正(体素水平阈值P<0.01,簇水平P<0.05);事后分析显示,刺激前TRD组DC值高于对照组,TRD组刺激后DC值明显低于刺激前(t=2.531、-4.029,P均<0.016);TRD组在前扣带回膝部/眶回内侧部刺激前后的DC差值与RRS、SDS评分呈负相关(r=-0.132,P=0.042;r=-0.389,P=0.023)。结论 TRD除情绪中枢存在功能异常外,还发现与奖赏及认知功能损害有关;ta VNS对情绪为主的相关脑区存在即刻调节作用。

Purpose To investigate the instant brain effect of transcutaneous auricular vagus nerve stimulation(taVNS) on treatmentresistant depression(TRD). Materials and Methods Thirty-four TRD patients were prospectively enrolled in four hospitals including Guang’anmen Hospital, China Academy of Traditional Chinese Medical Sciences, Xuanwu Hospital and Tsinghua University Yuquan Hospital from September 2018 to January 2020, and healthy volunteers(control group, n=34) were enrolled online during the same period. The scores of 17-item Hamilton depression scale(HAMD-17), Hamilton anxiety scale(HAMA), self-rating depression scale(SDS), self-rating anxiety scale(SAS), ruminative response scale(RRS) were recorded for every subject, and all subjects were then stimulated by taVNS for 30 minutes,and the rest stating functional MRI data were collected twice before and after stimulation immediately, respectively. By using the method of degree centrality(DC), the DC values were further compared between TRD group and control group. The correlation between DC difference(post stimulation-pre stimulation) and HAMD-17, HAMA, SDS, SAS and RRS scores was analyzed respectively. Results The DC values in the left parahippocampal gyrus/amygdala/nucleus accumbens, bilateral dorsolateral prefrontal lobe gyrus(left middle frontal gyrus, right middle frontal gyrus/superior frontal gyrus) in TRD group were significantly higher than those in control group, while in left middle occipital/superior occipital gyrus were significantly lower in TRD. There were significantly differences between the two groups before and after the stimulation in anterior cingulate gyrus in the pregenual/medial orbital gyrus(Gaussian random field correction, voxel P<0.01, cluster P<0.05),and post-hoc analysis showed that the DC value of TRD group before stimulation was significantly higher than those of control group, and the DC value of TRD group after stimulation was significantly lower than before(t=2.531,-4.029, all P<0.016). The DC difference(post-pre) of the TRD patients in this area was negatively correlated with the SDS, RRS scores(r=-0.132, P=0.042;r=-0.389, P=0.023). Conclusion TRD shows several abnormal functional brain network nodes associated with emotion dysfunction, reward deficit and cognitive impairment.ta VNS elicits an immediate effect on brain regions associated with emotional regulation.