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Stereological Analysis of Amygdala Neuron Number in Autism
Open accessAbstract
The amygdala is one of several brain regions suspected to be pathological in autism. Previously, we found that young children with autism have a larger amygdala than typically developing children. Past qualitative observations of the autistic brain suggest increased cell density in some nuclei of the postmortem autistic amygdala. In this first, quantitative stereological study of the autistic brain, we counted and measured neurons in several amygdala subdivisions of 9 autism male brains and 10 age-matched male control brains. Cases with comorbid seizure disorder were excluded from the study. The amygdaloid complex was outlined on coronal sections then partitioned into five reliably defined subdivisions: (1) lateral nucleus, (2) basal nucleus, (3) accessory basal nucleus, (4) central nucleus, and (5) remaining nuclei. There is no difference in overall volume of the amygdala or in individual subdivisions. There are also no changes in cell size. However, there are significantly fewer neurons in the autistic amygdala overall and in its lateral nucleus. In conjunction with the findings from previous magnetic resonance imaging studies, the autistic amygdala appears to undergo an abnormal pattern of postnatal development that includes early enlargement and ultimately a reduced number of neurons. It will be important to determine in future studies whether neuron loss in the amygdala is a consistent characteristic of autism and whether cell loss occurs in other brain regions as well.
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“Neuronal densities are higher in layers I-III of area 24a in the left hemisphere, neuronal size is reduced in all layers of area 24b, and neuronal packing density is reduced in layers V-VI in area 24c, consistent with previously reported reductions in neuronal density in the FG and amygdala [318, 362].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [318]
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BackgroundResultAge- and sex-specific fear conditioning deficits in mice lacking Pcdh10, an Autism Associated Gene
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“Interestingly, another structure affected in ASD patients is the amygdala, which has fewer neurons compared to normal individuals (Schumann and Amaral, 2006) and could explain some of the cognitive and social deficits characterized by ASD.”
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“We opted to report soma area rather than volume given that three-dimensional measures of soma volume and cell shape are not optimal in the stereological literature (Schumann and Amaral 2006; Gittins and Harrison 2011) due to the fixed orientation of the tissue sections.”
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“Among these regions, the amygdala has long received much attention in ASD research based on divergent lines of evidence; for example, the amygdala works as a hub for brain regions associated with social perception and social affiliation (50), which are affected in individuals with ASD; amygdala-damaged monkeys show ab…”
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“146,147 We explored the association between social trait judgment from participants and the neural responses of the amygdala and hippocampus acquired from an independent group of neurosurgical patients without ASD, and whether this association is diminished in participants with ASD compared to…”
BackgroundDelayed Development of the Claustrum in Autism
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“Structural amygdala abnormalities such as increased cell density (20), reduced neuron number (21) and changes in volume (22) have been observed in ASD and at least some of these changes are agerelated.”
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“…of the prefrontal cortex (Amina et al., 2021; Ariza et al., 2018; Hashemi et al., 2017) and decreased number of neurons in other brain areas including the fusiform gyrus (van Kooten et al., 2008), the amygdala (Schumann & Amaral, 2006), and the cerebellum were reported in ASD (Skefos et al., 2014).”
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“Additional anatomical imaging studies have reported larger volumes of both white and gray matter in the frontal cortex [13], larger volumes of the caudate nucleus even after covarying for overall brain size [14,15], and abnormal volumes (usually larger) of the amygdala and hippocampus [16,17].”
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Hanson, K. L., Lew, C. H., Hrvoj-Mihić, B., Cuevas, D., Greiner, D. M. Z., Groeniger, K. M., Edler, M. K., Halgren, E., Bellugi, U., Raghanti, M. A., et al. (2020) · Brain Structure and Function · doi:10.1007/s00429-020-02055-0 · Cited by 9
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“Furthermore, studies have indicated fewer neurons in the amygdala of individuals diagnosed with ASD compared to controls [22].”
BackgroundMAFT-SO: A novel multi-atlas fusion template based on spatial overlap for ASD diagnosis
Ma, Y., Mu, X., Zhang, T., & Zhao, Y. (2024) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2024.104714 · Cited by 7
Hanson, K. L., Avino, T. A., Taylor, S. L., Murray, K. D., & Schumann, C. M. (2025) · Molecular Autism · doi:10.1186/s13229-025-00684-y · Cited by 9
“Additionally, the amygdala is enlarged in children with ASD, with an increased number of neurons and dendritic spines relative to neurotypical children [82–85] followed by a loss of neurons and spine density in adulthood [85, 86].”
Self-citationWiese, A.-S., Needham, E. K., Noer, C. L., Balsby, T. J. S., Dabelsteen, T., & Pakkenberg, B. (2018) · Brain Structure and Function · doi:10.1007/s00429-018-1606-4 · Cited by 7
“Stereological quantifications of the human amygdala found 3,240,000 (± 520,000) neurons in BLA and 360,000 (± 80,000) in CeA (Shumann and Amaral 2006).”
BackgroundInfluentialWegiel, J., Brown, W. T., Fauci, G. L., Adayev, T., Kascsak, R. J., Kascsak, R., Flory, M. J., Kaczmarski, W., Kuchna, I., Nowicki, K., et al. (2018) · Autism Research · doi:10.1002/aur.2003 · Cited by 7
Weston, C. S. E. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00336 · Cited by 7
“, 2017b), cellular findings of reduced amygdala neuron numbers (Schumann and Amaral, 2006) or amygdala neuron density (Wegiel et al.”
BackgroundMadarnas, C., Villalba, N., Soriano, D., & Brusco, A. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00092 · Cited by 7
“Moreover, these results could be linked to clinical evidence showing that patients with autism have an increase in anxiety and a lower number of neurons in this structure (Schumann and Amaral, 2006).”
Neurobiology meets genomic science: The promise of human-induced pluripotent stem cells
Stevens, H. E., Mariani, J., Coppola, G., & Vaccarino, F. M. (2012) · Development and Psychopathology · doi:10.1017/s095457941200082x · Cited by 7
“Together with studies suggesting abnormal early volume growth and neuron number in amygdala (Schumann & Amaral, 2006; Schumann et al., 2004) and hippocampus (Lawrence, Kemper, Bauman, & Blatt, 2010), converging evidence now supports the hypothesis that ASDs may involve an early alteration in…”
BackgroundTwo-dimensional analysis of the supragranular layers in autism spectrum disorder
Karst, A. T., & Hutsler, J. J. (2016) · Research in Autism · doi:10.1016/j.rasd.2016.09.004 · Cited by 7
A network of networks approach for modeling interconnected brain tissue-specific networks
Kawakubo, H., Matsui, Y., Kushima, I., Ozaki, N., & Shimamura, T. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz032 · Cited by 7
Discrete Cortical Neuropathology in Autism Spectrum Disorders
Uppal, N., & Hof, P. R. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-391924-3.00022-3 · Cited by 7
Prise en charge des troubles de la communication : La Plateforme de Communication Alternative
Ader, M., Blache, P., & Rauzy, S. (2008) · HAL · Cited by 7
Neurodevelopmental Disorders: Autism Spectrum Disorder
Thom, R. P., Friedman, N. D. B., Nasir, R. H., Politte, L. C., Nowinski, L. A., & McDougle, C. J. (2023) · Springer eBooks · doi:10.1007/978-3-030-42825-9_36-1 · Cited by 8
Simas, T., & Suckling, J. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00353 · Cited by 7
A comparison of cell density and serotonergic innervation of the amygdala among four macaque species
Jones, D. N., ERWIN, J. M., Sherwood, C. C., Hof, P. R., & Raghanti, M. A. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.25048 · Cited by 6
“Additionally, neuron density is significantly lower in the lateral nucleus of individuals diagnosed with autism spectrum disorder (ASD) compared to healthy controls (Schumann & Amaral, 2006; Wegiel et al., 2014).”
BackgroundOfogh, S. N., Rasoolijazi, H., Ananloo, E. S., Shahrivar, Z., Joghataei, M. T., Sadeghi, B., Bozorgmehr, A., & Alizadeh, F. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01783-6 · Cited by 6
Morová, M., & Kršková, L. (2021) · Physiological Research · doi:10.33549/physiolres.934570 · Cited by 6
“Significantly fewer neurons were counted in the autistic amygdala compared to the control and the authors concluded that the amygdala undergoes atypical development in individuals with autism (Schumann and Amaral 2006).”
BackgroundCasanova, M. F. (2015) · Contemporary clinical neuroscience · doi:10.1007/978-1-4939-2190-4_8 · Cited by 6
“The small neurons reported by Bauman and Kemper in various regions of the limbic system may represent, as they stated, a “developmental phenotype.””
InfluentialNeurodevelopmental Disorders: Autism Spectrum Disorder
Thom, R. P., Friedman, N. D. B., Nasir, R. H., Politte, L. C., Nowinski, L. A., & McDougle, C. J. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_36 · Cited by 6
Vers une théorie clinique intégrée des désordres de la constellation autisitique
Gepner, B. (2012) · Développements · doi:10.3917/devel.010.0005 · Cited by 9
Engrailed2 and Cerebellar Development in the Pathogenesis of Autism Spectrum Disorders
Rossman, I. T., & DiCicco-Bloom, E. M. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-489-0_1 · Cited by 6
Semendeferi, K. (2018) · Interaction Studies Social Behaviour and Communication in Biological and Artificial Systems · doi:10.1075/is.17046.sem · Cited by 6
Autism and Asperger’s Syndrome: A Cognitive Neuroscience Perspective
Townsend, J., & Westerfield, M. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1364-7_10 · Cited by 6
“When present, limbic system abnormality involved increased packing density of neurons and reduction in neuron sizes or a reduced number of neurons [18].”
BackgroundPsychosocial Treatments for Children with Autism Spectrum Disorder
Kim, H. (2016) · Hanyang Medical Reviews · doi:10.7599/hmr.2016.36.1.27 · Cited by 8
“amygdala [17,19,20], reduced activity in the brain’s temporal and frontal lobes when performing language and motor tasks [21], and”
BackgroundCoocurrencia entre ansiedad y autismo. Las hipótesis del error social y de la carga alostática
Pérez, I. P. (2013) · Revista de Neurología · doi:10.33588/rn.56s01.2012652 · Cited by 9
“Las evidencias microscópicas de los estudios de neuropatología muestran un aumento de la densidad de las células neuronales, neuronas anormalmente pequeñas, y una disminución del número de neuronas en la amígdala [76,93-95], así como una reducción de las ramificaciones dendríticas del hipocampo [96].”
BackgroundThe Male Prevalence in Autism Spectrum Disorders: Hypotheses on its Neurobiological Basis
Keller, F., & Ruta, L. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1272-5_2 · Cited by 5
“Brain regions showing more robust neuroanatomical alterations, in vivo or post-mortem, include the temporal cortex, the hippocampus, the amygdala and the cerebellum (reviewed in Courchesne et al., 2005; Keller and Persico, 2003; Palmen et al, 2004; Schumann and Amaral, 2006).”
BackgroundPAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder
Goodrich, M., Armour, A. C., Panchapakesan, K., You, X., Devaney, J., Knoblach, S. M., Sullivan, C. A. W., Herrero, M. J., Gupta, A. R., Vaidya, C. J., et al. (2018) · Autism Research · doi:10.1002/aur.2051 · Cited by 5
The Developmental Neuropathology of Autism
Kemper, T. L. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1272-5_5 · Cited by 5
“Using modern stereology, Schumann and Amaral (2006) were unable to confirm the presence of an increased neuronal packing density and decreased neuronal size in the amygdala of nine autistic individuals.”
BackgroundMolecular Pathways within Autism Spectrum Disorder Endophenotypes
Briuglia, S., Calabrò, M., Capra, A. P., Briguori, S., Rosa, M. A. L., & Crisafulli, C. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01782-7 · Cited by 5
Microbiota-Gut-Brain-Axis and Autism Spectrum DisordersPreprint
Srikantha, P., & Mohajeri, M. H. (2018) · Preprints.org · doi:10.20944/preprints201811.0171.v1 · Cited by 4
“autism, so the changes observed in the amygdala could be responsible for ASD-like behaviour in GF mice [84].”
BackgroundSchumann, C. (2021) · Springer eBooks · doi:10.1007/978-3-319-91280-6_208 · Cited by 5
Self-citationHolford, T. W., Letourneau, K. N., Von-Walter, C., Moncaleano, D., Loomis, C. L., & Bolton, M. M. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1597131 · Cited by 5
“…disrupted in ASD, including social anxiety and social engagement, and in ASD patients there is evidence of an altered growth trajectory of amygdala nuclei and an altered fMRI response to fearful stimuli (Nordahl et al., 2012; Schumann et al., 2004; Schumann and Amaral, 2006; Kliemann et al., 2010).”
Metadata
- Authors
- Schumann, C. M., & Amaral, D. G.
- Affiliations
- University of California, Davis (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-07-19
- Volume
- 26
- Issue
- 29
- Pages
- 7674-7679
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674270
- OpenAlex
- W2087838692
- Cited by
- 413
- References
- 35
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 12 · 2023: 18 · 2022: 19 · 2021: 20 · 2020: 20 · 2019: 16 · 2018: 17 · 2017: 25 · 2016: 26 · 2015: 25 · 2014: 31 · 2013: 26 · 2012: 23
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Miami
- National Institutes of Health (MH41479)
- National Institute of Mental Health (MH-41479)
- 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
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- autism spectrum disorder, amygdala, neuron number, neuronal loss, lateral nucleus, central nucleus, postnatal brain development, brain volume, postmortem brain
- MeSH terms
- Adolescent, Adult, Amygdala, Autistic Disorder, Cadaver, Cell Count, Child, Humans, Male, Neurons, Case-Control Studies
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