Wang Mingqia, Chen Xiaoyu, Hu Yiru, Zhou Yangling, Wang Chengyu, Zheng Wei, Liu Weijian, Lan Xiaofeng, Ning Yuping, Zhang Bin
PsyNI Lab, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, Guangdong, China.
Depress Anxiety. 2022 May;39(5):352-362. doi: 10.1002/da.23238. Epub 2021 Dec 28.
Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce.
This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis.
In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders.
These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.
最近，一种抑郁症动物模型显示，N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂氯胺酮通过阻断外侧缰核（Hb）中依赖NMDAR的爆发式放电，产生快速起效的抗抑郁作用。然而，来自人体研究的证据仍然很少。
本研究探讨了在氯胺酮治疗前后，被诊断为单相或双相抑郁症的有反应者和无反应者中Hb静息态功能连接（FC）的变化。反应被定义为在第13天（第六次输注后24小时）时，与基线评分相比，蒙哥马利-艾斯伯格抑郁量表总分降低≥50%。进行相关性分析，以确定症状改善与上述成像分析中检测到的显著不同脑区信号之间的关联。
在事后的感兴趣区域分析中，与无反应者相比，有反应者（2周时蒙哥马利-艾斯伯格量表降低≥50%）中观察到Hb与默认模式网络的几个枢纽（包括角回、楔前叶、内侧前额叶皮质和颞中皮质）之间的基线FC增强。
这些初步研究结果可能提示了一种潜在的神经机制，通过该机制氯胺酮通过下调缰核与默认模式网络部分的异常功能连接，发挥其强大的抗抑郁疗效。
