Palmen Saskia J M C, van Engeland Herman, Hof Patrick R, Schmitz Christoph
Rudolf Magnus Institute of Neuroscience, Department of Child and Adolescent Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Brain. 2004 Dec;127(Pt 12):2572-83. doi: 10.1093/brain/awh287. Epub 2004 Aug 25.
Autism is currently viewed as a largely genetically determined neurodevelopmental disorder, although its underlying biological causes remain to be established. In this review, we examine the available neuropathological literature on autism and discuss the findings that have emerged. Classic neuropathological observations are rather consistent with respect to the limbic system (nine of 14 studied cases showed increased cell packing density and smaller neuronal size), the cerebellum (21 of 29 studied cases showed a decreased number of Purkinje cells, and in all of five cases that were examined for age-related morphological alterations, these changes were found in cerebellar nuclei and inferior olive) and the cerebral cortex (>50% of the studied cases showed features of cortical dysgenesis). However, all reported studies had to contend with the problem of small sample sizes, the use of quantification techniques not free of bias and assumptions, and high percentages of autistic subjects with comorbid mental retardation (at least 70%) or epilepsy (at least 40%). Furthermore, data from the limbic system and on age-related changes lack replication by independent groups. It is anticipated that future neuropathological studies hold great promise, especially as new techniques such as design-based stereology and gene expression are increasingly implemented and combined, larger samples are analysed, and younger subjects free of comorbidities are investigated.
目前，自闭症被视为一种主要由基因决定的神经发育障碍，尽管其潜在的生物学原因仍有待确定。在这篇综述中，我们研究了现有的关于自闭症的神经病理学文献，并讨论了已出现的研究结果。经典的神经病理学观察结果在边缘系统方面相当一致（14例研究病例中有9例显示细胞堆积密度增加且神经元尺寸较小）、小脑方面（29例研究病例中有21例显示浦肯野细胞数量减少，在所有接受年龄相关形态学改变检查的5例病例中，这些变化均在小脑核和下橄榄核中发现）以及大脑皮层方面（超过50%的研究病例显示皮质发育异常特征）。然而，所有已报道研究都不得不应对样本量小、使用存在偏差和假设的量化技术以及患有合并智力障碍（至少70%）或癫痫（至少40%）的自闭症受试者比例高的问题。此外，来自边缘系统的数据以及与年龄相关的变化缺乏独立研究小组的重复验证。预计未来的神经病理学研究前景广阔，特别是随着基于设计的体视学和基因表达等新技术越来越多地得到应用和结合，分析更大的样本，以及对无合并症的年轻受试者进行研究。
