Cincinnati Children's Hospital Medical Center (CCHMC), Division of Developmental and Behavioral Pediatrics, Ohio, USA.
Autism Res. 2011 Oct;4(5):317-35. doi: 10.1002/aur.216. Epub 2011 Aug 31.
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 [Risi et al., 2006]. 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 for elucidating genetic and toxicological contributions to impairments in social function [Halladay et al., 2009]. Behavioral tests have been developed that are relevant to autism [Crawley, 2004, 2007], including measures of repetitive behaviors [Lewis, Tanimura, Lee, & Bodfish, 2007; Moy et al., 2008], social behavior [Brodkin, 2007; Lijam et al., 1997; Moretti, Bouwknecht, Teague, Paylor, & Zoghbi, 2005], and vocal communication [D'Amato et al., 2005; Panksepp et al., 2007; Scattoni et al., 2008]. Advances also include development of high-throughput measures of mouse sociability that can be used to reliably compare inbred mouse strains [Moy et al., 2008; Nadler et al., 2004], as well as measures of social reward [Panksepp & Lahvis, 2007] and empathy [Chen, Panksepp, & Lahvis, 2009; Langford et al., 2006]. 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.
在缺乏可用于诊断 ASD 的分子生物标志物的情况下,目前的诊断工具依赖于对行为的临床评估。 对人类受试者的研究成功地利用了标准化的诊断工具,包括临床医生对父母的访谈和对儿童自身的直接观察[Risi 等人,2006 年]。 但是,由于临床仪器是半结构化的,并且严重依赖于动态的社会过程和临床技能,因此这些测量结果并不一定直接适用于对 ASD 病因的实验研究。 自闭症神经生物学的研究需要实验动物模型。 老鼠特别有助于阐明遗传和毒理学对社会功能障碍的贡献[Halladay 等人,2009 年]。 已经开发出与自闭症相关的行为测试[Crawley,2004 年,2007 年],包括重复性行为的测量[Lewis,Tanimura,Lee 和 Bodfish,2007 年; Moy 等人,2008 年],社会行为[Brodkin,2007 年; Lijam 等人,1997 年; Moretti,Bouwknecht,Teague,Paylor 和 Zoghbi,2005 年]和发声交流[D'Amato 等人,2005 年; Panksepp 等人,2007 年; Scattoni 等人,2008 年]。 进展还包括开发高通量的小鼠社交能力测量方法,可用于可靠地比较近交系小鼠[Moy 等人,2008 年; Nadler 等人,2004 年],以及社交奖励的测量[Panksepp 和 Lahvis,2007 年]和同理心[Chen,Panksepp 和 Lahvis,2009 年; Langford 等人,2006 年]。 随着与 ASD 遗传关联直接相关的基因靶向小鼠的不断产生,仍然迫切需要利用一套全面的小鼠行为测试,以便对与 ASD 相关的社交困难进行全面评估。 本文以共享情感障碍为例,探讨了临床和基础科学家之间在充分考虑转化框架内进行合作的潜在途径。