Department of Psychiatry, University of California, San Francisco, San Francisco, California 94121, USA.
Neurotherapeutics. 2010 Jul;7(3):232-40. doi: 10.1016/j.nurt.2010.05.011.
Autism is a heterogeneous disorder involving complex mechanisms and systems occurring at diverse times. Because an individual child with autism may have only a subset of all possible abnormalities at a specific time, it may be challenging to identify beneficial effects of an intervention in double-blind, randomized, controlled trials, which compare the mean responses to treatments. Beneficial effects in a small subset of children may be obscured by the lack of effect in the majority. We review the evidence for several potential model systems of biochemical abnormalities that may contribute to the etiology of autism, we describe potential biomarkers or treatment targets for each of these abnormalities, and we provide illustrative treatment trials using this methodology. Potential model systems include immune over and under reactivity, inflammation, oxidative stress, free fatty acid metabolism, mitochondrial dysfunction, and excitotoxicity. Including potential biomarkers and targeted treatments in clinical trials for autism provides a potential method for limiting the heterogeneity of enrolled subjects, which may improve the power of studies to identify beneficial effects of treatments while also improving the understanding of the disease.
自闭症是一种异质性疾病，涉及复杂的机制和系统，发生在不同的时间。由于自闭症儿童在特定时间可能只有所有可能异常的一部分，因此在双盲、随机、对照试验中识别干预措施的有益效果可能具有挑战性，这些试验比较了治疗的平均反应。在大多数情况下缺乏效果可能会掩盖少数儿童的有益效果。我们回顾了可能导致自闭症病因的几种潜在生化异常的模型系统的证据，我们描述了这些异常的每个潜在生物标志物或治疗靶点，并提供了使用这种方法的治疗试验的说明。潜在的模型系统包括免疫过度和反应不足、炎症、氧化应激、游离脂肪酸代谢、线粒体功能障碍和兴奋性毒性。在自闭症临床试验中纳入潜在的生物标志物和靶向治疗为限制入组患者的异质性提供了一种潜在方法，这可能会提高研究识别治疗有益效果的能力，同时也提高对疾病的理解。
