Department of Anatomy & Neuroscience, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu, Shizuoka 431-3192, Japan.
Med Hypotheses. 2013 Apr;80(4):368-72. doi: 10.1016/j.mehy.2013.01.002. Epub 2013 Feb 1.
Autism is a pervasive developmental disorder that is characterized by the behavioral traits of impaired social cognition and communication, and repetitive and/or obsessive behavior and interests. Although there are many theories and speculations about the pathogenetic causes of autism, the disruption of the serotonergic system is one of the most consistent and well-replicated findings. Recently, it has been reported that placenta-derived serotonin is the main source in embryonic day (E) 10-15 mouse forebrain, after that period, the serotonergic fibers start to supply serotonin into the forebrain. E 10-15 is the very important developing period, when cortical neurogenesis, migration and initial axon targeting are processed. Since all these events have been considered to be involved in the pathogenesis of autism and they are highly controlled by serotonin signals, the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. I, thus, postulate a hypothesis that placenta-derived hypo-serotonin situations in the developing forebrain cause autism. The hypothesis is as follows. Various factors, such as inflammation, dysfunction of the placenta, together with genetic predispositions cause a decrease of placenta-derived serotonin levels. The decrease of placenta-derived serotonin levels leads to hypo-serotonergic situations in the forebrain of the fetus. The paucity of serotonin in the forebrain leads to mis-wiring in important regions which are responsible for the theory of mind. The paucity of serotonin in the forebrain also causes over-growth of serotonergic fibers. These disturbances result in network deficiency and aberration of the serotonergic system, leading to the autistic phenotypes.
自闭症是一种普遍存在的发育障碍，其行为特征为社交认知和沟通受损、重复和/或强迫行为和兴趣。虽然有许多关于自闭症发病原因的理论和推测，但血清素能系统的紊乱是最一致和复制最多的发现之一。最近有报道称，胎盘衍生的血清素是胚胎第 10-15 天（E）小鼠前脑中的主要来源，在此之后，血清素能纤维开始将血清素供应到前脑中。E 10-15 是非常重要的发育时期，在此期间，皮质神经发生、迁移和初始轴突靶向发生。由于所有这些事件都被认为与自闭症的发病机制有关，而且它们都受到血清素信号的高度控制，因此当考虑自闭症的发病机制时，胎盘衍生的血清素缺乏应该具有潜在的重要性。因此，我提出了一个假设，即发育前脑中胎盘衍生的低血清素情况会导致自闭症。假设如下。各种因素，如炎症、胎盘功能障碍，加上遗传易感性，导致胎盘衍生的血清素水平下降。胎盘衍生的血清素水平下降导致胎儿前脑中的血清素能情况低下。前脑中的血清素缺乏会导致负责心理理论的重要区域的布线错误。前脑中的血清素缺乏也会导致血清素能纤维过度生长。这些干扰导致网络缺乏和血清素能系统的异常，导致自闭症表型。
