Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms.
Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms.
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DOI：
10.1016/s2215-0366(16)00096-1
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Posner J
中科院分区：
文献类型：
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作者：
Gallo EF;Posner J
注意力缺陷多动障碍 (ADHD) 是一种神经发育障碍，其特征是注意力不集中以及多动或冲动的发育水平不适当。长期以来，其临床表现的异质性、对治疗的不同反应以及不同的预后表明了无数的潜在原因。在过去的十年中，临床和基础研究工作发现了许多与多动症相关的行为和神经生物学改变，从基因到高阶神经网络。在这里，我们通过关注与该疾病有关的神经回路来回顾多动症的神经生物学，并讨论回路异常与症状表现和治疗的关系。我们总结了与 ADHD 的发展可能相关的遗传变异的文献，以及这些变异如何反过来影响回路功能和相关行为。这些潜在的神经生物学因素是否与症状表现存在因果关系仍然悬而未决。因此，我们评估了旨在理清因果关系问题的努力，并展示了临床和临床前环境中向内表型细化的研究格局的转变。此外，我们回顾了正在开发的用于了解这种复杂疾病的神经生物学基础的方法，包括动物模型的使用、神经调节和药物成像研究。
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder including the use of animal models, neuromodulation, and pharmaco-imaging studies.