Consequences of variations in genes that affect dopamine in prefrontal cortex
Consequences of variations in genes that affect dopamine in prefrontal cortex
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DOI：
10.1093/cercor/blini082
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发表时间：
2007-09-01
期刊：
影响因子：
3.7
通讯作者：
Diamond, Adele
中科院分区：
文献类型：
--
作者：
Diamond, Adele
Patricia Goldman-Rakic在研究背外侧前额叶皮层的认知功能以及多巴胺在其中的关键作用方面发挥了开创性的作用。这里讨论的工作是建立在这一基础上的，包括：1）对预测前额叶多巴胺水平较低但大脑基本正常的儿童（苯丙酮尿症[PKU]治疗的儿童）的研究。这些研究改变了医疗指南，改善了儿童的生活。2)研究PKU儿童在出生后第一周内由于视网膜多巴胺减少和苯丙氨酸过量而导致的视觉障碍（对比敏感度和运动感知）。这些研究也改变了医疗指南。3)研究了典型发育儿童的工作记忆和抑制控制差异，这是由于儿茶酚-O-甲基转移酶（COMT）基因型的差异，它选择性地影响前额多巴胺水平。4)COMT基因型对老年人认知能力影响的性别差异研究5)关于注意缺陷多动障碍（ADHD）（包括多动）和注意力不集中型AND之间的根本差异的假设。假设这些疾病在受影响的神经系统、潜在遗传学、对药物的反应性、合并症以及认知和行为特征方面不同。这些听起来很不相干，但它们都是在帕特里夏·戈德曼-拉基奇奠定的基础上系统地发展起来的。
Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children's lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and AND of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic.