Department of Psychology, University of Amsterdam, 1018 WB Amsterdam, The Netherlands.
Biol Psychiatry. 2010 Apr 1;67(7):602-7. doi: 10.1016/j.biopsych.2009.10.010. Epub 2009 Nov 22.
The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development-early organogenesis-can explain this association. In humans early organogenesis is an embryonic stage, spanning Day 20 to Day 40 after fertilization, which is characterized by intense interactivity among body parts of the embryo. This implies that a single mutation or environmental disturbance affecting development at this stage can have several phenotypic effects (i.e., pleiotropic effects). Disturbances during early organogenesis can lead to many different anomalies, including limb deformities, craniofacial malformations, brain pathology, and anomalies in other organs. We reviewed the literature and found ample evidence for the association between autism and different kinds of physical anomalies, which agrees with the hypothesis that pleiotropic effects are involved in the development of autism. The proposed mechanism integrates findings from a variety of studies on autism, including neurobiological studies and studies on physical anomalies and prenatal influences on neurodevelopmental outcomes. The implication is that the origin of autism can be much earlier in embryologic development than has been frequently reported.
胚胎错误与自闭症发展之间的关联在文献中已经得到了认可，但这种关联的机制仍不清楚。我们提出，胚胎发育的一个非常早期和特定阶段——早期器官发生期的多效性效应可以解释这种关联。在人类中，早期器官发生是一个胚胎阶段，从受精后第 20 天到第 40 天，胚胎的各个部分之间存在强烈的相互作用。这意味着在这个阶段影响发育的单个突变或环境干扰可能会产生多种表型效应（即多效性效应）。早期器官发生期的干扰可能导致许多不同的异常，包括肢体畸形、颅面畸形、脑病理学和其他器官的异常。我们回顾了文献，发现了大量自闭症与不同类型的身体异常之间关联的证据，这与多效性效应参与自闭症发展的假设是一致的。所提出的机制整合了自闭症的各种研究结果，包括神经生物学研究以及身体异常和产前对神经发育结果影响的研究。这意味着自闭症的起源可能比经常报道的胚胎发育要早得多。
