The COMT Val158Met polymorphism modulates working memory performance under acute stress
The COMT Val158Met polymorphism modulates working memory performance under acute stress
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DOI：
10.1016/j.psyneuen.2012.03.014
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发表时间：
2012-11-01
影响因子：
3.7
通讯作者：
Fiebach, Christian J.
中科院分区：
文献类型：
--
作者：
Buckert, Magdalena;Kudielka, Brigitte M.;Fiebach, Christian J.
背景：关于认知和情绪表型研究最广泛的遗传多态之一是COMT Val158Met多态，它影响前额叶皮质(PFC)的多巴胺供应。PFC是工作记忆等高级认知功能的关键大脑结构，也是心理内分泌应激反应的重要调节部位和靶点。多巴胺被认为以一种倒U形的方式影响PFC功能。因此，前额叶多巴胺的应激相关增加被假设为对工作记忆成绩产生不同的影响，这取决于基因决定的PFC中的基线多巴胺水平。方法：33名COMT Val158Met基因纯合的健康年轻受试者从更大的预基因分型样本中选择。在暴露于实验室心理社会压力诱导范式(Trier Social Stress Test for Groups；TSST-G)后，他们进行了n-back工作记忆任务。结果：在压力下，Met纯合子的工作记忆表现显著低于Val纯合子。重要的是，这种基因效应仅限于n-back任务的中等难度水平。结论：我们的结果表明，工作记忆在应激状态下的表现受到前额叶多巴胺水平遗传变异的影响。更广泛地说，我们的结果指出了考虑基因、环境和任务变量之间复杂交互作用的重要性。(C)2012爱思唯尔有限公司。保留所有权利。
Background: One of the most widely studied genetic polymorphisms regarding cognitive and emotional phenotypes is the COMT Val158Met polymorphism that influences dopamine availability in the prefrontal cortex (PFC). The PFC is the key brain structure for higher cognitive functions such as working memory, as well as an important regulatory site and target of the psychoendocrine stress response. Dopamine is thought to influence PFC functions in an inverted u-shaped manner. Thus, a stress-related increase in prefrontal dopamine is hypothesized to exert differential effects on working memory performance depending on the genetically determined baseline dopamine level in the PFC.Method: Thirty-three healthy young subjects homozygous for the COMT Val158Met polymorphism were selected from a larger pre-genotyped sample. They performed an n-back working memory task after exposure to a laboratory psychosocial stress induction paradigm (The Trier Social Stress Test for Groups; TSST-G).Results: Under stress, working memory performance of Met homozygotes was significantly worse than working memory performance of Val homozygotes. Importantly, this genotype effect was restricted to the medium difficulty level of the n-back task.Conclusion: Our results demonstrate that working memory performance under stress is influenced by genetic variation in prefrontal dopamine levels. More generally, our results point to the importance of considering the complex interaction of genes, environment, and task variables. (c) 2012 Elsevier Ltd. All rights reserved.