The impact of COMT inhibition on behaviour and neural activity, and its modulation by genotype and acute stress.

COMT 抑制对行为和神经活动的影响及其基因型和急性应激的调节。

• 批准号: MR/K013092/1
• 负责人: Paul Harrison
• 金额: $ 59.68万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK013092%2F1
• 关键词: impact; COMT; inhibition; behaviour; neural

Dopamine is a chemical messenger important for many brain functions, including memory, emotion and motivation. It needs to be maintained at the right level for these functions to be optimal, and either too much or too little is harmful, as seen in various brain diseases. COMT is an enzyme, a biological catalyst, which destroys dopamine. As a result, dopamine levels are influenced by the activity of COMT. Some people have a genetic variant that gives them low COMT activity, whilst others have a variant that leads to high activity. COMT's activity can also be reduced by drugs which prevent it working (a 'COMT inhibitor'). We and others have shown that both of these influences on COMT activity (from the gene, and from the drug) can affect memory and how people take risks, because of COMT's effects on dopamine. Other studies suggest that COMT also affects people's emotional state. This grant aims to help us understand better the potential of COMT inhibitor drugs for treating psychiatric disorders, many of which include problems with memory, risk taking, and controlling emotion. First, we will measure how the drug and the genetic variant interact to affect people's emotions and how they deal with risk and reward. Second, there is evidence that the genetic variation in COMT affects how well people cope with stress, and stress can have negative effects on memory and emotional state. We will therefore study how this relationship is affected by the COMT inhibitor and what exactly is going on in the brain during and after a stressful situation. The results of these studies will help us understand much better the potential of COMT inhibitors as useful drugs for psychiatric disorders, and whether a person's genetic make-up affects how they respond to them. The research will also provide information of wider value about how COMT regulates dopamine and its abnormal function in brain diseases.

多巴胺是一种化学信使，对包括记忆、情感和动机在内的许多大脑功能都很重要。这些功能需要保持在正确的水平才能达到最佳，过多或过少都是有害的，就像在各种脑部疾病中所看到的那样。COMT是一种酶，一种生物催化剂，可以破坏多巴胺。因此，多巴胺水平受到COMT活性的影响。一些人的基因变异使他们的COMT活性较低，而另一些人的基因变异导致他们的活性较高。COMT的活性也可以通过阻止其发挥作用的药物(一种COMT抑制剂)来降低。我们和其他人已经证明，由于COMT对多巴胺的影响，这些对COMT活动的影响(来自基因和药物)都可以影响记忆和人们如何冒险。其他研究表明，COMT也会影响人们的情绪状态。这笔赠款旨在帮助我们更好地了解COMT抑制剂药物治疗精神障碍的潜力，其中许多包括记忆、冒险和情绪控制问题。首先，我们将测量药物和基因变体如何相互作用来影响人们的情绪，以及他们如何处理风险和回报。其次，有证据表明，COMT的遗传变异会影响人们应对压力的能力，而压力可能会对记忆和情绪状态产生负面影响。因此，我们将研究COMT抑制剂是如何影响这种关系的，以及在压力情况下大脑到底发生了什么。这些研究的结果将有助于我们更好地了解COMT抑制剂作为治疗精神疾病有用药物的潜力，以及一个人的基因构成是否会影响它们对它们的反应。这项研究还将提供关于COMT如何调节多巴胺及其在脑部疾病中的异常功能的更广泛价值的信息。

项目成果

Catechol-O-methyltransferase activity does not affect emotional processing in men.

儿茶酚-O-甲基转移酶活性不会影响男性的情绪处理。

• 发表时间: 2022
• 期刊: Journal of Psychopharmacology
• 影响因子: 4.1
• 作者: Martens MAG

Catechol-O-methyltransferase (COMT) influences the connectivity of the prefrontal cortex at rest.

• DOI: 10.1016/j.neuroimage.2012.11.059
• 发表时间: 2013-03
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Tunbridge, Elizabeth M.;Farrell, Sarah M.;Harrison, Paul J.;Mackay, Clare E.
• 通讯作者: Mackay, Clare E.

Catechol-O-methyltransferase activity does not influence emotional processing in men.

• DOI: 10.1177/02698811221089032
• 发表时间: 2022-06
• 期刊: Journal of psychopharmacology (Oxford, England)
• 作者: Martens MA;Dalton N;Scaife J;Harmer CJ;Harrison PJ;Tunbridge EM
• 通讯作者: Tunbridge EM

Supplementary_table - Supplemental material for It feels real: physiological responses to a stressful virtual reality environment and its impact on working memory

Supplementary_table - 感觉真实的补充材料：对有压力的虚拟现实环境的生理反应及其对工作记忆的影响

• DOI: 10.25384/sage.8864036
• 发表时间: 2019
• 作者: Martens M