Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system
Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system
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DOI：
10.1016/j.euroneuro.2013.03.009
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发表时间：
2013-11-01
影响因子：
5.6
通讯作者：
Bensenor, I. M.
中科院分区：
文献类型：
--
作者：
Brunoni, A. R.;Kemp, A. H.;Bensenor, I. M.
经颅直流电刺激(Tdcs)作为一种非药物治疗抑郁症(MDD)的方法已被广泛研究。虽然许多研究已经检验了抗抑郁药物的遗传预测因素，但这个问题仍有待于对tDCs进行调查。在目前的研究中，我们评估了BDNF Val66Met和5-HTT(5-HTTLPR)基因多态是否与tdcs抗抑郁反应相关。我们使用了一项因子试验的数据，该试验评估了tdcs和舍曲林的疗效，并招募了120名中到重度、不服用抗抑郁药的参与者。在本研究中，我们使用方差分析来评估BDNF(Val/Val与Met-Carry)和5-HTTLPR等位基因(长/长与短携带者)是否是tDCS(主动/假)和舍曲林(舍曲林/安慰剂)反应的预测因子。分别对这些多态进行了分析，并对其相互作用进行了分析。基因频率符合Hardy-Weinberg平衡。脑源性神经营养因子基因多态性与治疗反应无关。我们发现，5-HTTLPR预测了tDCs的影响，因为长/长纯合子与活动的tDCs相比显示出更大的改善，而短等位基因携带者则没有。还提出了长等位基因的活性-假性差异之间的剂量-反应关系。这些结果加强了5-羟色胺能系统在tdcs抗抑郁作用中的作用，并扩展了先前报道的tdcs的作用机制部分涉及5-羟色胺能受体。因此，我们假设tdcs是一种神经调节技术，通过调节5-羟色胺能系统对抑郁起作用，tdcs“自上而下”的抗抑郁作用在杏仁核过度活跃引起自下而上效应的脑网络中可能不是最佳的，就像在短载体中发生的那样。(C)2013年爱思唯尔和ECNP。版权所有。
Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. In the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS "top-down" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.