Courchesne Eric, Pierce Karen, Schumann Cynthia M, Redcay Elizabeth, Buckwalter Joseph A, Kennedy Daniel P, Morgan John
Department of Neurosciences, School of Medicine, University of California-San Diego, La Jolla, CA 92093, USA.
Neuron. 2007 Oct 25;56(2):399-413. doi: 10.1016/j.neuron.2007.10.016.
Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions.
尽管对自闭症的神经生物学研究已持续了二十多年,但这些研究大多是在临床症状出现10年、20年或更久之后才对大脑结构进行检查。导致自闭症的病理生物学机制仍然未知,但其特征可能在临床症状初现的生命最初几年最为明显。本综述着重介绍生命最初几年的神经生物学研究发现,并强调早期大脑过度生长是自闭症病理生物学的关键因素。我们推测,神经元数量过多可能是早期大脑过度生长的一个潜在原因,并导致神经模式形成和神经连接出现缺陷,局部和短距离皮层的过度活跃相互作用会阻碍大脑区域之间大规模、长距离相互作用的功能。由于大规模神经网络是社会情感和沟通功能的基础,这种大脑结构的改变可能与自闭症的早期临床表现有关。因此,自闭症或许还能为塑造早期神经连接模式并使高阶社会、情感和沟通功能成为可能的遗传和发育过程提供独特的见解。