Neuropathological findings in autism

Palmen, S. J. M. C.

doi:10.1093/brain/awh287

Cited by 527Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersChild Nutrition and Feeding Issues

Neuropathological findings in autism

Palmen, S. J. M. C.·2004·Brain

DOI 10.1093/brain/awh287

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Abstract

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.

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The most consistently reported neuropathology in autism is a reduction in cerebellar Purkinje cells.
“The most consistently reported neuropathology is a reduction in cerebellar Purkinje cells, the sole outflow of cerebellar cortex [6, 120].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [120]
Similar to the most consistent finding in humans, an increase in the frontal and parieto-temporal lobes and decreased volume of the cerebellar cortex were observed in one of three subgroups (group 1) identified among 26 investigated ASD mouse models.
“Similar to the most consistent finding in humans [94, 95], an increase in the frontal and parieto-temporal lobes and decreased volume of the cerebellar cortex were observed in one of the three subgroups (“group 1”) identified among the 26 investigated models [75].”
From Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism (2016) · cites this paper as [94]

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Authors: Palmen, S. J. M. C.
Affiliations: University Medical Center Utrecht (NL)
Corresponding author: Palmen, S. J. M. C.
Venue: Brain
Publisher: Oxford University Press (OUP)
Published: 2004-11-10
Volume: 127
Issue: 12
Pages: 2572-2583
ISSN: 0006-8950 (ISSN-L)
1460-2156
DOI: 10.1093/brain/awh287
OpenAlex: W2143865775
Cited by: 527
References: 114
Citations by year: 2026: 9 · 2025: 11 · 2024: 14 · 2023: 15 · 2022: 9 · 2021: 20 · 2020: 26 · 2019: 10 · 2018: 13 · 2017: 17 · 2016: 31 · 2015: 22 · 2014: 32 · 2013: 37 · 2012: 46
FWCI: 12.76
Type: journal article
Language: en
Open access: closed
Locations: Brain (publishedVersion)
PubMed (publishedVersion)
RWTH Publications (RWTH Aachen) (submittedVersion)
Funders: National Institutes of Health (n01hd013138-010)
National Institute of Mental Health (MH66392, P50MH066392)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01 HD 13138)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords: autism spectrum disorder, neuropathology, limbic system, cerebellum, Purkinje cells, cortical dysgenesis, neuron size, epilepsy, design-based stereology, gene expression
MeSH terms: Adolescent, Adult, Autistic Disorder, Brain, Cerebellum, Cerebral Cortex, Child, Humans, Limbic System, Magnetic Resonance Imaging

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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Neuropathological findings in autism

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