BACKGROUND Non-convulsive neurostimulation is a rapidly-developing alternative to traditional treatment approaches in depression. Modalities such as repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Direct Current Stimulation (tDCS), Vagal Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS) are now recognized as potential treatments. How non-convulsive neurostimulation interventions impact the neurohormonal and neuroimmune changes that accompany depression remains relatively unknown. If this type of intervention can drive endocrine, immune, as well symptom changes in depression, non-convulsive neurostimulation may represent a viable, multi-faceted treatment approach in depression. We were therefore interested to understand the state of the literature in this developing area. METHODS A systematic review of all studies that examined the impact of non-convulsive neurostimulation interventions on the hypothalamic-pituitary-adrenal (HPA) axis and immune function in the form of cytokine production in depression. RESULTS We identified 15 human studies, 9 that examined rTMS, 2 that examined tDCS, 2 that examined VNS and 2 that examined electroacupuncture. 11 animal studies were also identified, 3 that examined rTMS, 2 that examined DBS and 6 that examined electroacupuncture. All types of non-convulsive neurostimulation were able to revert the increases in cortisol, ACTH and other components of the HPA axis that are seen in depressed patients, as well as to modulate the levels of key cytokines known to be up-regulated in depression, such as IL-1β, IL-6 and TNF-α. Changes in the HPA axis and levels of cytokines in response to non-convulsive neurostimulation often did not correlate with change in depressive symptoms. Most studies were not controlled trials and thus, significant methodologic variability existed. Furthermore, many human studies lacked a sham stimulation comparator arm. We were unable to conduct relevant meta-analyses due to the design heterogeneities, heterogeneity in the reported outcome measures and the limited number of studies retrieved. Animal studies generally supported the findings of those in human, but again, significant variability in methodology and study design were evident. CONCLUSIONS Non-convulsive neurostimulation interventions show promise in their ability to alter the endocrine and immune disturbances that accompany depression. Further research, which includes blinded, sham-controlled comparator designs is required.

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非惊厥性神经刺激对抑郁症的内分泌和免疫作用：系统评价

背景非惊厥性神经刺激是一种快速发展的替代抑郁症传统治疗方法的方法。诸如重复经颅磁刺激 (rTMS)、经颅直流电刺激 (tDCS)、迷走神经刺激 (VNS) 和深部脑刺激 (DBS) 等方式现在被认为是潜在的治疗方法。非惊厥性神经刺激干预如何影响伴随抑郁症的神经激素和神经免疫变化仍然相对未知。如果这种类型的干预可以驱动内分泌、免疫以及抑郁症的症状变化，那么非痉挛性神经刺激可能代表一种可行的、多方面的抑郁症治疗方法。因此，我们有兴趣了解这个发展中地区的文献状况。方法 对所有研究的系统评价，这些研究检查了非惊厥性神经刺激干预对抑郁症中细胞因子产生形式的下丘脑 - 垂体 - 肾上腺 (HPA) 轴和免疫功能的影响。结果 我们确定了 15 项人体研究，其中 9 项检查 rTMS，2 项检查 tDCS，2 项检查 VNS 和 2 项检查电针。还确定了 11 项动物研究，其中 3 项检查了 rTMS，2 项检查了 DBS，6 项检查了电针。所有类型的非痉挛性神经刺激都能够逆转抑郁症患者中皮质醇、ACTH 和 HPA 轴其他成分的增加，以及调节已知在抑郁症中上调的关键细胞因子的水平，如 IL-1β、IL-6 和 TNF-α。HPA 轴的变化和细胞因子水平对非惊厥性神经刺激的反应通常与抑郁症状的变化无关。大多数研究不是对照试验，因此存在显着的方法学差异。此外，许多人体研究缺乏假刺激比较臂。由于设计异质性、报告结果测量的异质性以及检索到的研究数量有限，我们无法进行相关的荟萃分析。动物研究通常支持人类的研究结果，但同样，方法和研究设计的显着差异是显而易见的。结论 非惊厥性神经刺激干预在改变伴随抑郁症的内分泌和免疫紊乱的能力方面显示出前景。进一步的研究，包括盲法，