Clinical biomarkers carry great potential to enhance quality of life outcomes for those with autism spectrum disorder (ASD). Current biomarker research has set the stage for this breakthrough. At the federal level, the US Centers for Disease Control and National Institutes of Health Interagency Autism Coordinating Committee led the way in recognizing the need for biomarkers that facilitate ASD research. Significant public and private funding have been directed toward biomarker development over the last 5 to 7 years. As a result, major efforts in the US (e.g. Autism Biomarkers Consortium for Clinical Trials) and Europe (e.g. European Autism Interventions – A Multicentre Study for Developing New Medications) are underway and building off of prior biomarker work to identify etiological mechanisms, subgroup or stratify patients with ASD, detect early target engagement, enhance identification, evaluate interventions (e.g. with the Janssen Autism Knowledge Engine [JAKE ]), and track differential outcomes. This research opens the door to the development of autism biomarkers with everyday clinical utility. Studies have examined the potential for various molecular panels to detect ASD. While informative, these processes are quite distant from outcomes that matter to patients and families, and do not provide actionable information to guide minute-to-minute or day-to-day functional supports. Substantial etiological heterogeneity in ASD also decreases the likelihood that molecular and cellular measures will prove useful on their own, although it is possible that aggregation of measures across different levels of biological analysis could address this challenge. Neuroimaging is closer to behavior, but has its own set of drawbacks, including: cost; availability; need for specialized expertise and technology; difficulty collecting data in young/impaired populations; limited scalability; technical challenges, etc.; and, in some cases, ethical concerns (e.g. sedation in young children). Focusing on technologies that are closer to the behavioral manifestations of ASD may increase both the value of biomarkers and impact clinical practice and everyday life. We submit that technologies enabling quantitative assays of physiological, cognitive, and behavioral processes will translate into more feasible, scalable, and cost-effective approaches that enable clinicians to enhance the lives of patients and families while at the same time advancing basic research. As illustrated in Figure S1 (online supporting information), such technologies are lower cost; require minimal training to administer and less technical expertise for scoring and interpretation; can be collected unobtrusively and rapidly or with ongoing passive monitoring; and make minimal requirements on the person being assessed. Taken together, we submit that clinically useful biomarkers merit increased attention from funders and researchers. We recognize that molecular, cellular, and neural circuitry biomarkers will continue to be essential to understanding etiological heterogeneity, stratifying ASD into more tractable subgroups or dimensions, and assaying target engagement. We further acknowledge the potential role of neuroimaging methods to understand circuit level patterns that contribute to core autism domains, and the possibility that high-dimensional algorithms could have diagnostic or prognostic utility. Our hope is that, as strategic efforts are made to advance progress in biomarker development, strong consideration also be given to the potential for clinical utility. Emerging technologies capable of objectively quantifying physiological, cognitive, and behavioral processes can facilitate this new frontier. As will involving people with ASD and their families in identifying, developing, testing, and improving future biomarkers to maximize their utility, effectiveness, and impact.

中文翻译：

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在自闭症谱系障碍中开发更多临床有用的生物标志物

临床生物标志物具有提高自闭症谱系障碍 (ASD) 患者生活质量的巨大潜力。当前的生物标志物研究为这一突破奠定了基础。在联邦层面，美国疾病控制中心和美国国立卫生研究院自闭症协调委员会率先认识到需要促进 ASD 研究的生物标志物。在过去的 5 到 7 年中，大量的公共和私人资金被用于生物标志物的开发。因此，美国（例如自闭症生物标志物临床试验联盟）和欧洲（例如欧洲自闭症干预——开发新药物的多中心研究）的主要努力正在进行中，并建立在先前的生物标志物工作的基础上，以确定病因机制、亚组或对 ASD 患者进行分层，检测早期目标参与、增强识别、评估干预措施（例如使用 Janssen Autism Knowledge Engine [JAKE]）并跟踪差异结果。这项研究为开发具有日常临床用途的自闭症生物标志物打开了大门。研究已经检验了各种分子组检测 ASD 的潜力。虽然信息量很大，但这些过程与对患者和家人很重要的结果相去甚远，并且不提供可操作的信息来指导每分钟或每天的功能支持。ASD 中的大量病因异质性也降低了分子和细胞测量本身被证明有用的可能性，尽管跨不同生物分析水平的测量聚合可能会解决这一挑战。神经影像学更接近于行为，但有其自身的一系列缺点，包括：成本；可用性; 需要专业知识和技术；难以在年轻/受损人群中收集数据；有限的可扩展性；技术挑战等；在某些情况下，还有伦理问题（例如幼儿镇静）。专注于更接近 ASD 行为表现的技术可能会增加生物标志物的价值并影响临床实践和日常生活。我们认为，能够对生理、认知和行为过程进行定量分析的技术将转化为更可行、可扩展和更具成本效益的方法，使临床医生能够改善患者和家庭的生活，同时推进基础研究。如图 S1（在线支持信息）所示，此类技术成本较低；需要最少的管理培训和较少的评分和解释技术专业知识；可以不显眼且快速地或通过持续的被动监测进行收集；并对被评估人提出最低要求。总之，我们认为临床上有用的生物标志物值得资助者和研究人员更多地关注。我们认识到，分子、细胞和神经回路生物标志物对于理解病因异质性、将 ASD 分层为更易于处理的亚组或维度以及分析目标参与度将继续是必不可少的。我们进一步承认神经影像学方法在理解有助于核心自闭症领域的电路级模式方面的潜在作用，以及高维算法具有诊断或预后效用的可能性。我们希望，随着为推进生物标志物开发的进展做出战略性努力，也应充分考虑临床效用的潜力。能够客观量化生理、认知和行为过程的新兴技术可以促进这一新领域的发展。让 ASD 患者及其家人参与识别、开发、测试和改进未来的生物标志物，以最大限度地提高其效用、有效性和影响。能够客观量化生理、认知和行为过程的新兴技术可以促进这一新领域的发展。让 ASD 患者及其家人参与识别、开发、测试和改进未来的生物标志物，以最大限度地提高其效用、有效性和影响。能够客观量化生理、认知和行为过程的新兴技术可以促进这一新领域的发展。让 ASD 患者及其家人参与识别、开发、测试和改进未来的生物标志物，以最大限度地提高其效用、有效性和影响。