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COMT val158met 对老年人大脑直流电刺激诱导认知增强的影响。

Impact of COMT val158met on tDCS-induced cognitive enhancement in older adults.

机构信息

Department of Neurology, University Medicine Greifswald, Greifswald, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Department of Neurology, NeuroCure Clinical Research Center, Berlin, Germany.

Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.

出版信息

Behav Brain Res. 2021 Mar 5;401:113081. doi: 10.1016/j.bbr.2020.113081. Epub 2021 Jan 4.

Abstract

BACKGROUND

Previous studies suggest that genetic polymorphisms and aging modulate inter-individual variability in brain stimulation-induced plasticity. However, the relationship between genetic polymorphisms and behavioral modulation through transcranial direct current stimulation (tDCS) in older adults remains poorly understood.

OBJECTIVE

Link individual tDCS responsiveness, operationalized as performance difference between tDCS and sham condition, to common genetic polymorphisms in healthy older adults.

METHODS

106 healthy older participants from five tDCS-studies were re-invited to donate blood for genotyping of apoliproprotein E (APOE: ε4 carriers and ε4 non-carriers), catechol-O-methyltransferase (COMT: val/val, val/met, met/met), brain-derived neurotrophic factor (BDNF: val/val, val/met, met/met) and KIdney/BRAin encoding gene (KIBRA: C/C, C/T, T/T). Studies had assessed cognitive performance during tDCS and sham in cross-over designs. We now asked whether the tDCS responsiveness was related to the four genotypes using a linear regression models.

RESULTS

We found that tDCS responsiveness was significantly associated with COMT polymorphism; i.e., COMT val carriers (compared to met/met) showed higher tDCS responsiveness. No other significant associations emerged.

CONCLUSION

Using data from five brain stimulation studies conducted in our group, we showed that only individual variation of COMT genotypes modulated behavioral response to tDCS. These findings contribute to the understanding of inherent factors that explain inter-individual variability in functional tDCS effects in older adults, and might help to better stratify participants for future clinical trials.

摘要

背景

先前的研究表明,遗传多态性和衰老调节了脑刺激诱导可塑性的个体间变异性。然而,遗传多态性与经颅直流电刺激(tDCS)在老年人中的行为调节之间的关系仍知之甚少。

目的

将个体 tDCS 反应性(定义为 tDCS 与假刺激条件之间的表现差异)与健康老年人中的常见遗传多态性联系起来。

方法

从五个 tDCS 研究中重新邀请了 106 名健康的老年参与者捐献血液进行载脂蛋白 E(APOE:ε4 携带者和 ε4 非携带者)、儿茶酚-O-甲基转移酶(COMT:val/val、val/met、met/met)、脑源性神经营养因子(BDNF:val/val、val/met、met/met)和 Kidney/Brain encoding gene(KIBRA:C/C、C/T、T/T)的基因分型。这些研究采用交叉设计评估了 tDCS 和假刺激期间的认知表现。我们现在询问 tDCS 反应性是否与四种基因型有关,使用线性回归模型。

结果

我们发现 tDCS 反应性与 COMT 多态性显著相关;即 COMT val 携带者(与 met/met 相比)表现出更高的 tDCS 反应性。没有出现其他显著关联。

结论

使用我们小组进行的五项脑刺激研究的数据,我们表明只有 COMT 基因型的个体变异调节了对 tDCS 的行为反应。这些发现有助于理解解释老年人功能性 tDCS 效果个体间变异性的内在因素,并可能有助于更好地为未来的临床试验分层参与者。

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