Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults
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INTRODUCTION: Characterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism. RESULTS: Our data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology. CONCLUSIONS: The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.
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The convergence of neuronal size distributions between ASD and controls in adulthood likely reflects opposing developmental trajectories, with nuclear volume increasing with age in ASD in half of examined areas while control nuclear volumes decrease in most areas.
“This is likely a result of opposing developmental trajectories, with nuclear volume increasing with age in ASD in half of the examined brain areas, whereas nuclear volumes are reduced in most brain areas of controls as they aged [377].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [377]
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Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536 · see citing works
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- Authors
- Wegiel, J., Flory, M., Kuchna, I., Nowicki, K., Ma, S. Y., Imaki, H., Wegiel, J., Frackowiak, J., Kolecka, B. M., Wierzba-Bobrowicz, T., London, E., Wisniewski, T., Hof, P. R., & Brown, W. T.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Wegiel, Jarek
- Venue
- Acta Neuropathologica Communications
- Published
- 2015-01-17
- Volume
- 3
- Issue
- 1
- Pages
- 2-2
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC4302585
- OpenAlex
- W2135720729
- Cited by
- 47
- References
- 106
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 8 · 2016: 2 · 2015: 2
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (AS073234)
- Autism Speaks
- Office for People With Developmental Disabilities
- National Institute on Aging (P30AG008051)
- National Institute of Mental Health (R24MH068855)
- National Institute of Child Health and Human Development
- 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, brain development, lifespan changes, subcortical structures, cerebellum, brainstem, archicortex, interindividual variability, adolescents, young adults
- MeSH terms
- Adolescent, Adult, Age Factors, Autistic Disorder, Brain, Cell Nucleus, Child, Child, Preschool, Cytoplasm, Female, Humans, Male, Middle Aged, Neurons, Severity of Illness Index, Case-Control Studies, Young Adult
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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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