经皮耳穴迷走神经电刺激治疗难治性及非难治性抑郁症的脑效应比较

Comparison of brain effects of transcutaneous auricular vagus nerve stimulation for treatment-resistant and nontreatment-resistant depression

目的:比较经皮耳穴迷走神经电刺激(taVNS)治疗难治性抑郁症(TRD)与非难治性抑郁症(nTRD)患者的脑功能效应机制。方法:纳入24例TRD(TRD组)与31例nTRD(nTRD组)患者,2组均行8周的taVNS治疗,治疗前后均行静息态fMRI扫描。采用17项汉密尔顿抑郁量表(HAMD-17)作为主要临床疗效指标,冗思量表(RRS)为次要临床疗效指标。采用混合效应分析比较2组治疗前后的低频振幅(ALFF)差异。结果:治疗后2组HAMD-17评分均显著下降,nTRD组RRS评分显著下降(均P<0.001)。fMRI结果显示,治疗前nTRD组在左侧丘脑/下丘脑/苍白球及右侧初级视觉皮质ALFF值均显著低于TRD组(均P<0.001)。治疗后,nTRD组左侧中央后回与右侧中央前回ALFF值显著升高(P<0.005,P<0.001),右侧岛叶ALFF值显著降低(P<0.001);TRD组左侧中央后回ALFF值显著升高(P<0.005),右侧岛叶ALFF值显著降低(P<0.001)。混合效应分析显示,左侧眶部额中回与右侧小脑Crus2是2组治疗前后的差异脑区(均P<0.005);nTRD组治疗后左侧眶部额中回与右侧小脑Crus2的ALFF值均显著降低(P<0.05,P<0.001),TRD组治疗后左侧眶部额中回与右侧小脑Crus2的ALFF值均显著升高(P<0.001,P<0.05)。结论:taVNS治疗抑郁症有效,但对TRD患者反刍思维改善方面疗效欠佳。TRD与nTRD的脑机制存在差异。taVNS可调制抑郁症关键脑区,如岛叶、眶部额中回,小脑可能与taVNS调制抑郁症的脑机制有关,这可能是其治疗TRD与nTRD的多个靶点;taVNS治疗TRD与nTRD可能存在不同的脑效应机制。这些不同的脑区突出了抑郁症治疗的复杂性和个体化性质,需进一步研究以充分了解TRD和nTRD的神经生物学基础。

Objective:To compare the brain effects of transcutaneous auricular vagus nerve stimulation(taVNS)on brain function in patients with treatment-resistant depression(TRD)and non-treatment-resistant depression(nTRD).Methods:24 patients with TRD and 31 patients with nTRD were enrolled.All patients received taVNS treatment for eight weeks.Resting-state fMRI(fMRI)was performed before and after treatment.The 17-item Hamilton Rating Scale for Depression(HAMD-17)was used as the primary clinical efficacy indicator,while the Ruminative Response Scale(RRS)served as the secondary indicator.The amplitude of low-frequency fluctuation(ALFF)values before and after treatment between the two groups were compared by mixed effect analysis.Results:After treatment,the HAMD-17 scores of the two groups and the RRS scores of the nTRD group showed a significant reduction(both P<0.001).In the fMRI results,ALFF values of the left thalamus/hypothalamus/globus pallidum and the right primary visual cortex in the nTRD group were significantly lower than those of the TRD group before treatment(both P<0.001).After treatment,the nTRD group demonstrated a significant increase in ALFF values in the left posterior central gyrus and the right precentral gyrus and a significant decrease in ALFF value in the right insular lobe(all P<0.05);the TRD group demonstrated a significant increase in ALFF value in the left posterior central gyrus and a significant decrease in ALFF value in the right insular lobe(both P<0.05).Mixed-effect analysis results showed that the left orbitofrontal gyrus and right cerebellar Crus2 were the different brain regions between the TRD group and the nTRD group before and after treatment;the nTRD group had a significant decrease in ALFF values in the left orbitofrontal gyrus and right cerebellar Crus2 after treatment,while the TRD group had a significant increase in ALFF values in the left orbitofrontal gyrus and the right cerebellum Crus2(all P<0.05).Conclusions:TaVNS is effective in treating depression,but not effective in improving rumination in TRD patients.The brain mechanisms of TRD and nTRD are different.TaVNS has the ability to modulate crucial brain regions involved in depression,including the insula and orbitofrontal medial gyrus.The cerebellum may play a role in the brain mechanism of taVNS modulation of depression.These distinct brain regions may be multiple targets for the treatment of TRD and nTRD.The brain effect mechanisms of taVNS in the treatment of TRD and nTRD are different.These distinct mechanisms highlight the complexities and individualized nature of depression treatment,and further research is needed to fully understand the neurobiological basis of TRD and nTRD.