Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
CNS Neurol Disord Drug Targets. 2012 May;11(3):209-21. doi: 10.2174/187152712800672481.
Catechol-O-methyltransferase (COMT) is a promising target for modulation of cognitive functions and dysfunctions. COMT dominates the regulation of dopamine metabolism in the prefrontal cortex. Thus, COMT effects are particularly evident in prefrontal cortex-dependent cognitive functions including executive control, working memory, attentional control and long-term memory. This has been determined by both genetic and pharmacological studies that we will highlight in the present review. In particular, we will discuss how common functional variants of the COMT gene may predict individual variation in selective cognitive abilities and vulnerability to cognitive deficits that characterize several neuropsychiatric disorders. Moreover, COMT genetic variants represent one source of individual differences in the cognitive responses to medications such as those used in psychiatric illnesses. COMT genetic testing may then predict some cognitive dysfunctions often seen in certain psychiatric illnesses even from presymptomatic stages and the efficacy/dosage of drugs used to treat them. The consideration of COMT-dependent differences may be important for the development of more efficient personalized healthcare.
儿茶酚-O-甲基转移酶（COMT）是调节认知功能和功能障碍的有前途的靶点。COMT 主导前额叶皮层中多巴胺代谢的调节。因此，COMT 的作用在前额叶皮层依赖的认知功能中尤为明显，包括执行控制、工作记忆、注意力控制和长期记忆。这是通过遗传和药理学研究确定的，我们将在本综述中重点介绍。特别是，我们将讨论 COMT 基因的常见功能变体如何预测个体在选择性认知能力上的差异，以及对几种神经精神疾病特征的认知缺陷的易感性。此外，COMT 遗传变异是个体对药物（如精神疾病中使用的药物）的认知反应存在差异的一个来源。因此，COMT 基因检测可以预测某些精神疾病中经常出现的一些认知功能障碍，甚至在出现症状前阶段和用于治疗这些疾病的药物的疗效/剂量方面。考虑 COMT 依赖性差异对于开发更有效的个性化医疗保健可能很重要。
