Henriquez-Henriquez Marcela, Zamorano-Mendieta Francisco, Rothhammer-Engel Francisco, Aboitiz Francisco
Centro de Investigaciones Medicas Pontificia Universidad Catolica de Chile, Santiago de Chile, Chile.
Rev Neurol. 2010;50(2):109-16.
The influence of genetics in attention deficit hyperactivity disorder (ADHD) is well confirmed. However, identification of the specific genes involved in the pathogenesis of the disorder has proved to be difficult. Some authors suggest that the statistical power of molecular genetic studies could improve by replacing the diagnosis of the disease on the basis of clinical phenotype by quantitative risk markers closer to underlying genetic pathophysiology and gene action. Such markers, generically called 'endophenotypes', have attracted considerable scientific interest. When searching for new endophenotypes, priority must be given to markers that are based or anchored in the actual neuro-cognitive etiological models for ADHD.
To describe the principal concepts involved in current models of ADHD and to briefly discuss their implication for identification of endophenotypes in ADHD.
Herein we discuss the evolution of causal models for ADHD, from simple core deficit models to complex multiple-pathways models. Additionally, we describe the thalamo-cortico-striatal circuits, which is the common anatomic substrate for all causal models for ADHD.
Thalamo-cortico-striatal circuits are recognized as the anatomic and functional substrate for all causal neuro-cognitive models for ADHD. In this context, any electrophysiological, behavioral, neuro-humoral or anatomic marker related with functions commanded by such system (mainly executive functions and reward functions) could be a promising endophenotype for ADHD. Special interest must be taken in markers that potentially allow us to 'dissect' parallels etiological pathways, like electrophysiological parameters or functional neuroimages. Finally, the psychometric properties of potential endophenotypes must be adequate for a reliable, sensitive and specific quantification.
遗传学在注意力缺陷多动障碍（ADHD）中的影响已得到充分证实。然而，要确定该疾病发病机制中涉及的具体基因却颇具难度。一些作者认为，通过用更接近潜在遗传病理生理学和基因作用的定量风险标志物取代基于临床表型的疾病诊断，分子遗传学研究的统计效力可能会提高。这类标志物通常被称为“内表型”，已引起了相当大的科学关注。在寻找新的内表型时，必须优先考虑基于ADHD实际神经认知病因模型或与之相关的标志物。
描述当前ADHD模型中涉及的主要概念，并简要讨论它们对ADHD内表型识别的意义。
在此，我们讨论ADHD因果模型的演变，从简单的核心缺陷模型到复杂的多途径模型。此外，我们描述了丘脑 - 皮质 - 纹状体回路，它是所有ADHD因果模型共有的解剖学基础。
丘脑 - 皮质 - 纹状体回路被认为是所有ADHD因果神经认知模型的解剖学和功能基础。在这种情况下，任何与该系统所支配功能（主要是执行功能和奖赏功能）相关的电生理、行为、神经体液或解剖学标志物都可能是ADHD有前景的内表型。对于那些可能使我们“剖析”平行病因途径的标志物，如电生理参数或功能性神经影像，必须给予特别关注。最后，潜在内表型的心理测量特性必须足以进行可靠、敏感和特异的量化。
