Placebo effects and neuromodulation for depression: a meta-analysis and evaluation of shared mechanisms
Placebo effects and neuromodulation for depression: a meta-analysis and evaluation of shared mechanisms
复制标题
DOI：
10.1038/s41380-021-01397-3
复制
发表时间：
2021-12-14
影响因子：
11
通讯作者：
Santarnecchi, Emiliano
中科院分区：
文献类型：
--
作者：
Burke, Matthew J.;Romanella, Sara M.;Santarnecchi, Emiliano
越来越多的证据表明，安慰剂效应可以有意义地调节大脑。然而，很少有人考虑这些变化是否可能与抑郁症治疗的靶向区域/回路重叠，以及这种重叠对安慰剂对照临床试验中测量疗效的影响。在本系统性综述和荟萃分析中，我们检索了PubMed/Medline和Google Scholar中关于安慰剂效应的功能性MRI和PET神经影像学研究。纳入了招募健康受试者和患者人群的研究。提取神经成像坐标并纳入激活可能性估计（ALE）荟萃分析。然后，我们搜索了经颅磁刺激（TMS）和脑深部电刺激（DBS）治疗抑郁症的干预性研究，并提取了目标坐标，用于与安慰剂效应图进行比较空间分析。在识别的1169篇文章中，纳入了34项安慰剂效应的神经影像学研究。有三个显著的激活集群：左背外侧前额叶皮层（DLPFC）（x =-41，y = 16，z = 34），左膝下前扣带皮层（sgACC）/腹侧纹状体（x =-8，y = 18，z =-15）和右喙前扣带皮层（rACC）（x = 4，y = 42，z = 10）。有两个显著的失活簇：右侧基底神经节（x = 20，y = 2，z = 7）和右侧背侧前扣带皮层（dACC）（x = 1，y =-5，z = 45）。用于抑郁症治疗的TMS和DBS目标分别与左侧DLPFC簇和sgACC簇重叠。我们的研究结果确定了健康个体和患者人群中与安慰剂效应有关的一组常见大脑区域，并提供了这些区域与抑郁症治疗目标重叠的证据。我们模拟了这种重叠的统计影响，并证明了对该领域临床试验疗效测量的重要影响。
There is growing evidence that placebo effects can meaningfully modulate the brain. However, there has been little consideration of whether these changes may overlap with regions/circuits targeted by depression treatments and what the implications of this overlap would be on measuring efficacy in placebo-controlled clinical trials. In this systematic review and meta-analysis, we searched PubMed/Medline and Google Scholar for functional MRI and PET neuroimaging studies of placebo effects. Studies recruiting both healthy subjects and patient populations were included. Neuroimaging coordinates were extracted and included for Activation Likelihood Estimation (ALE) meta-analysis. We then searched for interventional studies of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) for depression and extracted target coordinates for comparative spatial analysis with the placebo effects maps. Of 1169 articles identified, 34 neuroimaging studies of placebo effects were included. There were three significant clusters of activation: left dorsolateral prefrontal cortex (DLPFC) (x = -41, y = 16, z = 34), left sub-genual anterior cingulate cortex (sgACC)/ventral striatum (x = -8, y = 18, z = -15) and the right rostral anterior cingulate cortex (rACC) (x = 4, y = 42, z = 10). There were two significant deactivation clusters: right basal ganglia (x = 20, y = 2, z = 7) and right dorsal anterior cingulate cortex (dACC) (x = 1, y = -5, z = 45). TMS and DBS targets for depression treatment overlapped with the left DLPFC cluster and sgACC cluster, respectively. Our findings identify a common set of brain regions implicated in placebo effects across healthy individuals and patient populations, and provide evidence that these regions overlap with depression treatment targets. We model the statistical impacts of this overlap and demonstrate critical implications on measurements of clinical trial efficacy for this field.