Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression
Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression
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DOI：
10.1016/j.euroneuro.2017.12.012
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发表时间：
2018-03-01
影响因子：
5.6
通讯作者：
Kranaster, Laura
中科院分区：
文献类型：
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作者：
Hoyer, Carolin;Sartorius, Alexander;Kranaster, Laura
Klotho是一种具有多效性的体液因子。最值得注意的是，Klotho缺乏症与包括伴随衰老的器官表现（包括动脉粥样硬化和认知障碍）的表型相关。关于Klotho在情感障碍中的作用的研究很少，这是令人惊讶的，因为抑郁症与加速的细胞衰老以及在Klotho缺乏症中观察到的衰老相关表型和合并症有关。基于这些理由，我们调查了Klotho水平的脑脊液（CSF）和血清中的8名老年患者接受电休克治疗（ECT）的严重抑郁症。我们假设ECT作为一种高效的抗抑郁治疗可以提高Klotho水平。我们发现ECT前后CSF Klotho之间存在显著差异（792.5 pg/ml vs. 991.3 pg/ml，p=0.0020），但血清Klotho无差异（602.5 vs. 594.3，p=0.32）。此外，CSF Klotho增加与每例患者中进行的单次ECT治疗次数呈正相关（F1，6）=7.84，p=0.031）。同时，我们的小样本探索性研究结果表明，ECT对Klotho的中枢神经系统特异性影响，这反过来可能参与介导ECT的抗抑郁作用。我们建议调制的神经炎症过程，这已被归因于病理生理相关性的概念框架内的神经炎症假说的抑郁症，通过ECT作为一个潜在的机制，Klotho是增强响应于治疗。进一步的临床前和临床研究应旨在精确鉴定Klotho在抑郁症中的作用。(C)2017 Elsevier B.V.和ECNP。All rights reserved.
Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5 pg/ml vs. 991.3 pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system -specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder. (C) 2017 Elsevier B.V. and ECNP. All rights reserved.