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Fetit, Rana; Hillary, Robert F.; Price, David J.; Lawrie, Stephen M.
Neuroscience & biobehavioral reviews/Neuroscience and biobehavioral reviews, October 2021, 2021-10-00, 20211001, Letnik: 129Journal Article
Display omitted •Autism and related disorders display an overlap in presentation and neuropathology.•Impaired synaptic, metabolic, proliferation, apoptosis and immune pathways are repeatedly implicated.•Dysregulated non-coding RNAs and aberrant epigenetic profiles are consistently reported.•Strong evidence for GABAergic, glutamatergic and glial dysfunction is provided.•The cerebellum and frontal cortex are most consistently implicated. 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.
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