The autism diagnosis in translation: shared affect in children and mouse models of ASD.
The autism diagnosis in translation: shared affect in children and mouse models of ASD.
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DOI：
10.1002/aur.216
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发表时间：
2011-10
期刊：
影响因子：
4.7
通讯作者：
Lahvis, Garet P.
中科院分区：
文献类型：
--
作者：
Bishop, Somer L.;Lahvis, Garet P.
近年来，自闭症谱系障碍（ASD）的评估和诊断程序有了显着改善。标准化的诊断工具已经开发出来，促进了临床医生之间诊断实践的一致性。对于临床研究人员来说，这些工具通过提供评估ASD症状的标准化指标，促进了不同站点之间的合作。然而，由于ASD仍然是一种基于行为定义的诊断，因此在实验室动物中建模ASD社会行为存在重大挑战。为了更有效地研究ASD症状和行为的原因，需要开发新的方法来测量可应用于非人类物种的社会行为。重要的是，虽然临床医生和患者之间的口头对话是临床诊断不可或缺的，但它不能用于动物模型的研究。然而，类似自闭症的社会互动的观察可以在动物中建模。在这方面，临床和基础科学专业人员之间的沟通是必要的，以打破复杂的诊断为单位的社会损害，可以更可行地衡量不同物种。本文介绍了一位动物研究者和一位临床心理学家之间的讨论。以共享情感为例，我们探索了提高动物模型效用的潜在途径，以使我们更好地理解ASD中社会障碍的机制。在缺乏可用于诊断ASD的分子生物标志物的情况下，当前的诊断工具依赖于行为的临床评估。人类受试者的研究工作已经成功地利用了标准化的诊断工具，其中包括临床医生与父母的访谈和对儿童本身的直接观察。然而，由于临床工具是半结构化的，并且严重依赖于动态的社会过程和临床技能，因此这些措施的分数不一定直接用于ASD原因的实验研究。自闭症的神经生物学研究需要实验动物模型。在这方面，小鼠特别适用于阐明对社会功能损伤的遗传和毒理学贡献。行为测试已经开发出与自闭症相关的测试，包括重复行为，社会行为和声音交流的测量。研究进展还包括开发了高通量的小鼠社会性测量方法，可用于可靠地比较近交系小鼠品系，以及社会奖励和同情心的测量方法。随着与ASD中的遗传联系直接相关的小鼠基因靶向小鼠的不断产生，仍然迫切需要利用全套小鼠行为测试，以全面评估与ASD相关的社会困难的范围。以共同情感障碍为例，本文探讨了临床和基础科学家之间合作的潜在途径，在充分考虑的翻译框架。
In recent years, there have been significant improvements in assessment and diagnostic procedures for autism spectrum disorders (ASD). Standardized diagnostic instruments have been developed, promoting consistent diagnostic practices among clinicians. For clinical researchers, these instruments have facilitated collaborations across different sites by providing standardized metrics with which to evaluate ASD symptoms. Nevertheless, because ASD remains a diagnosis that is defined on the basis of behavior, there are significant challenges associated with modeling ASD social behaviors in laboratory animals. In order to more effectively study the causes of ASD symptoms and behaviors, there is a need to develop new ways of measuring social behaviors that can be applied to non-human species. Critically, while verbal dialogue between the clinician and patient is integral to clinical diagnoses, it cannot be employed for studies of animal models. However, observations of autistic-like social interactions can be modeled in animals. In this regard, communication between professionals in the clinical and basic sciences is necessary to break down the complex diagnosis into units of social impairment that can be more feasibly measured in different species. This paper presents a discussion between an animal researcher and a clinical psychologist. Using shared affect as an example, we explore potential avenues for increasing the utility of animal models to move us toward a better understanding of the mechanisms underlying social impairments in ASD. In the absence of molecular biomarkers that can be used to diagnose ASD, current diagnostic tools depend upon clinical assessments of behavior. Research efforts with human subjects have successfully utilized standardized diagnostic instruments, which include clinician interviews with parents and direct observation of the children themselves. However, because clinical instruments are semi-structured and rely heavily on dynamic social processes and clinical skill, scores from these measures do not necessarily lend themselves directly to experimental investigations into the causes of ASD. Studies of the neurobiology of autism require experimental animal models. Mice are particularly useful, in this regard, for elucidating genetic and toxicologjcal contributions to impairments in social function. Behavioral tests have been developed that are relevant to autism, including measures of repetitive behaviors, social behavior, and vocal communication. Advances also include development of high-throughput measures of mouse sociability that can be used to reliably compare inbred mouse strains, as well as measures of social reward and empathy. With continued generation of mouse gene-targeted mice that are directly relevant to genetic linkages in ASD, there remains an urgent need to utilize a full suite of mouse behavioral tests that allows for a comprehensive assessment of the spectrum of social difficulties relevant to ASD. Using impairments in shared affect as an example, this paper explores potential avenues for collaboration between clinical and basic scientists, within an amply considered translational framework.
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