Simons Initiative for the Developing Brain, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Neurosci Biobehav Rev. 2021 Oct;129:35-62. doi: 10.1016/j.neubiorev.2021.07.014. Epub 2021 Jul 14.
Post-mortem studies allow for the direct investigation of brain tissue in those with autism and related disorders. Several review articles have focused on aspects of post-mortem abnormalities but none has brought together the entire post-mortem literature. Here, we systematically review the evidence from post-mortem studies of autism, and of related disorders that present with autistic features. The literature consists of a small body of studies with small sample sizes, but several remarkably consistent findings are evident. Cortical layering is largely undisturbed, but there are consistent reductions in minicolumn numbers and aberrant myelination. Transcriptomics repeatedly implicate abberant synaptic, metabolic, proliferation, apoptosis and immune pathways. Sufficient replicated evidence is available to implicate non-coding RNA, aberrant epigenetic profiles, GABAergic, glutamatergic and glial dysfunction in autism pathogenesis. Overall, the cerebellum and frontal cortex are most consistently implicated, sometimes revealing distinct region-specific alterations. The literature on related disorders such as Rett syndrome, Fragile X and copy number variations (CNVs) predisposing to autism is particularly small and inconclusive. Larger studies, matched for gender, developmental stage, co-morbidities and drug treatment are required.
尸检研究允许直接研究自闭症和相关障碍患者的脑组织。有几篇综述文章集中探讨了尸检异常的各个方面，但没有一篇文章将整个尸检文献汇集在一起。在这里，我们系统地回顾了自闭症和具有自闭症特征的相关障碍的尸检研究的证据。该文献由数量较少的小样本研究组成，但有几个非常一致的发现。皮质层基本未受干扰，但有明显的迷你柱数量减少和异常髓鞘形成。转录组学多次暗示突触、代谢、增殖、凋亡和免疫途径异常。有足够的复制证据表明非编码 RNA、异常表观遗传谱、GABA 能、谷氨酸能和神经胶质功能障碍与自闭症的发病机制有关。总的来说，小脑和额叶皮层最常被牵连，有时会显示出特定区域的改变。与自闭症相关的疾病（如雷特综合征、脆性 X 综合征和导致自闭症的拷贝数变异）的文献特别少且不一致。需要进行更大规模的研究，对性别、发育阶段、合并症和药物治疗进行匹配。
