Department of Physiology and Biophysics, 123 Sherman Hall, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, United States.
Cereb Cortex. 2024 May 2;34(13):94-103. doi: 10.1093/cercor/bhae050.
Autism (or autism spectrum disorder) was initially defined as a psychiatric disorder, with the likely cause maternal behavior (the very destructive "refrigerator mother" theory). It took several decades for research into brain mechanisms to become established. Both neuropathological and imaging studies found differences in the cerebellum in autism spectrum disorder, the most widely documented being a decreased density of Purkinje cells in the cerebellar cortex. The popular interpretation of these results is that cerebellar neuropathology is a critical cause of autism spectrum disorder. We challenge that view by arguing that if fewer Purkinje cells are critical for autism spectrum disorder, then any condition that causes the loss of Purkinje cells should also cause autism spectrum disorder. We will review data on damage to the cerebellum from cerebellar lesions, tumors, and several syndromes (Joubert syndrome, Fragile X, and tuberous sclerosis). Collectively, these studies raise the question of whether the cerebellum really has a role in autism spectrum disorder. Autism spectrum disorder is now recognized as a genetically caused developmental disorder. A better understanding of the genes that underlie the differences in brain development that result in autism spectrum disorder is likely to show that these genes affect the development of the cerebellum in parallel with the development of the structures that do underlie autism spectrum disorder.
自闭症(或自闭症谱系障碍)最初被定义为一种精神障碍,其可能的病因是母亲的行为(即极具破坏性的“冰箱母亲”理论)。直到几十年后,对大脑机制的研究才得以确立。神经病理学和影像学研究都发现自闭症谱系障碍患者的小脑存在差异,其中最广泛记录的是小脑皮质浦肯野细胞密度降低。对这些结果的流行解释是,小脑神经病理学是自闭症谱系障碍的一个关键原因。我们通过论证来挑战这一观点,如果浦肯野细胞数量减少对自闭症谱系障碍至关重要,那么任何导致浦肯野细胞丢失的情况也应该导致自闭症谱系障碍。我们将回顾小脑损伤、肿瘤和几种综合征(Joubert 综合征、脆性 X 综合征和结节性硬化症)引起的小脑损伤的数据。这些研究共同提出了一个问题,即小脑是否真的在自闭症谱系障碍中起作用。自闭症谱系障碍现在被认为是一种由基因引起的发育障碍。更好地了解导致自闭症谱系障碍的大脑发育差异的基因,很可能表明这些基因与导致自闭症谱系障碍的结构的发育平行地影响小脑的发育。