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自闭症的成因是什么?探索环境因素的影响。

What causes autism? Exploring the environmental contribution.

机构信息

Department of Community and Preventive Medicine, Department of Pediatrics, Children's Environmental Health Center, Mount Sinai School of Medicine, New York, USA.

出版信息

Curr Opin Pediatr. 2010 Apr;22(2):219-25. doi: 10.1097/MOP.0b013e328336eb9a.

Abstract

PURPOSE OF REVIEW

Autism is a biologically based disorder of brain development. Genetic factors--mutations, deletions, and copy number variants--are clearly implicated in causation of autism. However, they account for only a small fraction of cases, and do not easily explain key clinical and epidemiological features. This suggests that early environmental exposures also contribute. This review explores this hypothesis.

RECENT FINDINGS

Indirect evidence for an environmental contribution to autism comes from studies demonstrating the sensitivity of the developing brain to external exposures such as lead, ethyl alcohol and methyl mercury. But the most powerful proof-of-concept evidence derives from studies specifically linking autism to exposures in early pregnancy - thalidomide, misoprostol, and valproic acid; maternal rubella infection; and the organophosphate insecticide, chlorpyrifos. There is no credible evidence that vaccines cause autism.

SUMMARY

Expanded research is needed into environmental causation of autism. Children today are surrounded by thousands of synthetic chemicals. Two hundred of them are neurotoxic in adult humans, and 1000 more in laboratory models. Yet fewer than 20% of high-volume chemicals have been tested for neurodevelopmental toxicity. I propose a targeted discovery strategy focused on suspect chemicals, which combines expanded toxicological screening, neurobiological research and prospective epidemiological studies.

摘要

目的综述

自闭症是一种基于生物学的大脑发育障碍。遗传因素(突变、缺失和拷贝数变异)显然与自闭症的发病有关。然而,它们只占病例的一小部分,并且不容易解释关键的临床和流行病学特征。这表明早期环境暴露也有影响。本综述探讨了这一假设。

最近的发现

间接证据表明自闭症的发生与环境有关,这些证据来自于研究,表明发育中的大脑对外界暴露(如铅、乙醇和甲基汞)敏感。但最有力的概念验证证据来自于将自闭症与妊娠早期的暴露联系起来的研究——沙利度胺、米索前列醇和丙戊酸;母体风疹感染;以及有机磷杀虫剂氯吡硫磷。没有可信的证据表明疫苗会导致自闭症。

总结

需要扩大对自闭症的环境病因的研究。现在的孩子周围有数千种合成化学物质。其中 200 种对成人具有神经毒性,而在实验室模型中则有 1000 多种。然而,只有不到 20%的高容量化学品经过了神经发育毒性测试。我提出了一种针对可疑化学物质的有针对性的发现策略,该策略结合了扩展的毒理学筛选、神经生物学研究和前瞻性流行病学研究。

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