Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
Mol Psychiatry. 2018 May;23(5):1094-1112. doi: 10.1038/mp.2018.2. Epub 2018 Feb 27.
Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD. Major electronic databases were searched to identify preclinical and clinical studies that have investigated the effects of DBS on depression-related outcomes. Overall, 92 references met inclusion criteria, and have evaluated six unique DBS targets namely the subcallosal cingulate gyrus (SCG), nucleus accumbens (NAc), ventral capsule/ventral striatum or anterior limb of internal capsule (ALIC), medial forebrain bundle (MFB), lateral habenula (LHb) and inferior thalamic peduncle for the treatment of unrelenting TRD. Electrical stimulation of these pertinent brain regions displayed differential effects on mood transition in patients with TRD. In addition, 47 unique references provided preclinical evidence for putative neurobiological mechanisms underlying antidepressant effects of DBS applied to the ventromedial prefrontal cortex, NAc, MFB, LHb and subthalamic nucleus. Preclinical studies suggest that stimulation parameters and neuroanatomical locations could influence DBS-related antidepressant effects, and also pointed that modulatory effects on monoamine neurotransmitters in target regions or interconnected brain networks following DBS could have a role in the antidepressant effects of DBS. Among several neuromodulatory targets that have been investigated, DBS in the neuroanatomical framework of the SCG, ALIC and MFB yielded more consistent antidepressant response rates in samples with TRD. Nevertheless, more well-designed randomized double-blind, controlled trials are warranted to further assess the efficacy, safety and tolerability of these more promising DBS targets for the management of TRD as therapeutic effects have been inconsistent across some controlled studies.
虽然深部脑刺激（DBS）是治疗帕金森病（PD）、特发性震颤和运动障碍的一种既定治疗选择，但它在治疗难治性抑郁症（TRD）方面的有效性仍不清楚。在此，我们对 DBS 治疗难治性 TRD 的主要神经解剖靶点进行了综合回顾。本文的目的是批判性地讨论临床前研究和临床试验中确定的 DBS 产生抗抑郁作用的潜在机制，并确定考虑到 TRD 的急性和维持治疗，哪个脑靶点产生了最有希望的结果。主要电子数据库被搜索以确定研究 DBS 对抑郁相关结果影响的临床前和临床研究。总的来说，有 92 篇参考文献符合纳入标准，并评估了六个独特的 DBS 靶点，即：扣带回下脚（SCG）、伏隔核（NAc）、腹侧被盖区/腹侧纹状体或内囊前肢（ALIC）、内侧前脑束（MFB）、外侧缰核（LHb）和丘脑下脚，用于治疗顽固性 TRD。这些相关脑区的电刺激对 TRD 患者的情绪转变显示出不同的影响。此外，47 篇独特的参考文献提供了 DBS 应用于腹侧前额叶皮质、NAc、MFB、LHb 和丘脑底核的抗抑郁作用的潜在神经生物学机制的临床前证据。临床前研究表明，刺激参数和神经解剖位置可能会影响 DBS 相关的抗抑郁作用，并且还指出 DBS 后目标区域或相互连接的脑网络中的单胺能神经递质的调节作用可能在 DBS 的抗抑郁作用中发挥作用。在已经研究的几个神经调节靶点中，在 SCG、ALIC 和 MFB 的神经解剖框架内进行 DBS 治疗 TRD 患者时，产生了更一致的抗抑郁反应率。然而，需要更多设计良好的随机双盲对照试验来进一步评估这些更有希望的 DBS 靶点治疗 TRD 的疗效、安全性和耐受性，因为一些对照研究中的治疗效果不一致。
