The neuropathology of autism: A systematic review of post-mortem studies of autism and related disorders

Neurosci Biobehav Rev. 2021 Oct:129:35-62. doi: 10.1016/j.neubiorev.2021.07.014. Epub 2021 Jul 14.

Abstract

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.

Keywords: Autism; Autism Spectrum Disorder (ASD); Post-mortem studies; Systematic review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Autism Spectrum Disorder*
  • Autistic Disorder* / genetics
  • Autopsy
  • Brain
  • Cerebellum
  • DNA Copy Number Variations
  • Humans