Genetic and neurochemical modulation of prefrontal cognitive functions in children
Genetic and neurochemical modulation of prefrontal cognitive functions in children
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DOI：
10.1176/appi.ajp.161.1.125
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发表时间：
2004-01-01
影响因子：
17.7
通讯作者：
Gehlbach, L
中科院分区：
文献类型：
--
作者：
Diamond, A;Briand, L;Gehlbach, L
目的：儿茶酚o -甲基转移酶（COMT）基因影响多巴胺在前额皮质的作用时间。蛋氨酸多态性导致前额叶多巴胺分解较慢，与更好的成人前额叶皮质功能有关。作者研究了COMT基因多态性与儿童认知能力的关系。方法：对儿童进行认知任务测试，这些任务依赖于背外侧前额叶皮层，似乎对那里的多巴胺水平敏感（点状混合任务），依赖于该神经区域，但似乎对其多巴胺含量不敏感（自我有序指向），并依赖于其他神经系统（回忆记忆和心理旋转）。数据收集后，采集所有儿童的口腔拭子。提取DNA，用聚合酶链反应对COMT基因进行分型。结果：蛋氨酸多态性为纯合子的儿童在点混合任务中表现明显更好，而在其他任务中表现不佳。结论：研究结果提供了一个存在的证据，基因型差异可能与正常发育儿童的认知表现差异有关。作者达到了前所未有的特异性水平；通过任务的认知要求是否对多巴胺水平敏感，发现COMT多态性与与同一前额叶区域相关的任务的表现存在差异。这些结果挑战了公认的观念，因为多巴胺对依赖于前额皮质的某些认知功能很重要，所以它对所有人都很重要。不同认知能力对特定神经递质的不同敏感性可能使有针对性的药物干预成为可能。
Objective: The catechol O-methyltransferase (COMT) gene affects how long dopamine acts in the prefrontal cortex. The Methionine polymorphism, which results in a slower breakdown of prefrontal dopamine, is associated with better adult prefrontal cortex function. The authors investigated the relation between the COMT gene polymorphism and cognitive performance in children.Method: Children were tested on cognitive tasks that depend on the dorsolateral prefrontal cortex and seem to be sensitive to the level of dopamine there (dots-mixed task), depend on that neural region but appear insensitive to its dopamine content (self-ordered pointing), and depend on other neural systems (recall memory and mental rotation). After data collection, cheek swabs were obtained from all children. DNA was extracted and genotyped for the COMT gene with polymerase chain reaction.Results: Children who were homozygous for the Methionine polymorphism performed significantly better on the dots-mixed task but not on others.Conclusions: The findings provide an existence proof that genotypic differences can relate to differences in cognitive performance in typically developing children. The authors achieved a level of specificity never previously attempted; the COMT polymorphism was found to be differentially related to performance on tasks linked to the same prefrontal region by whether cognitive requirements of the tasks were sensitive to the level of dopamine found. These results challenge accepted notions that since dopamine is important for some cognitive functions dependent on the prefrontal cortex, it is important for all. The differential sensitivity of distinct cognitive abilities to specific neurotransmitters may make possible targeted pharmacological interventions.