Skip to main content
SpringerLink
Log in

Dynamic Brain Changes in Autism: Review of Telencephalic Structures

  • Reference work entry
Book cover Comprehensive Guide to Autism

Abstract

In this chapter of morphological differences in postmortem brains from autistic and normal individuals, we identified consistent reports of abnormalities in neuronal neurogenesis and neurodegeneration. Postmortem studies observed since 1985 found abnormalities throughout the brain, but for the sake of this chapter, our focus is on telencephalon, which includes cerebral cortex, amygdala and basal ganglion, and related pathways. Postmortem studies have examined cortical and subcortical regions, ventricular features and neurotransmitter, and neurotrophic factors. In this chapter we make several important observations on the development and progression of autism disorder derived from postmortem studies. (1) The changes in telencephalon occur in all cortical, subcortical, and connections between these regions. (2) There is accelerated growth and evidence of enhanced neurogenesis and brain size in children and toddlers. (3) There is evidence of neuropathology in brains from adolescents and adult patients. (4) Serotonin neurons, trophic factors, and glial cells appear to be involved in these developmental changes. The findings are grouped into three developmental stages: (1) neonate and toddlers (1–10 years), (2) adolescent (11–19 years), and (3) adult (20–60 years). Unfortunately, postmortem studies frequently have only a few cases and results may not be identified by the age of the donor. However, consistent findings were identified from the published studies we reviewed. We propose a hypothetical sequence of development events to describe autism. Serotonin fibers entering the telencephalon are increased: à increase in cell proliferation, neuronal and glial maturation in ventricles, and cortical columns; à increased brain size; à increased microglia activation and receptor downregulation; and trophic factor depletion à increase in neuronal dystrophy and degeneration. These steps are part of a neuroplasticity scheme and serve to help in understanding the dynamics of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,199.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31:137–45.

    Article  PubMed  Google Scholar 

  • Anderson GM, Horne WC, Chatterjee D, Cohen DJ. The hyperserotonemia of autism. Ann N Y Acad Sci. 1990;600:331–42.

    Article  PubMed  Google Scholar 

  • Azmitia EC. Serotonin neurons, neuroplasticity, and homeostasis of neural tissue. Neuropsychopharmacology. 1999;21(2 Suppl):33S–45.

    PubMed  Google Scholar 

  • Azmitia EC. Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull. 2001;56:413–24.

    Article  PubMed  Google Scholar 

  • Azmitia EC, Nixon R. Dystrophic serotonergic axons in neurodegenerative diseases. Brain Resour. 2008;1217:185–94.

    Article  Google Scholar 

  • Azmitia EC, Singh JS, Whitaker-Azmitia PM. Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharmacology. 2011a;60:1347–54.

    Article  PubMed  Google Scholar 

  • Azmitia EC, Singh JS, Hou XP, Wegiel J. Dystrophic serotonin axons in postmortem brains from young autism patients. Anat Records. 2011b;294:1653–62.

    Article  Google Scholar 

  • Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P. A clinicopathological study of autism. Brain. 1998;121:889–905.

    Article  PubMed  Google Scholar 

  • Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J,… Arango V. Antidepressants increase neural progenitor cells in the human hippocampus. Neurpsychopharm. 2009;34:2376–89

    Article  Google Scholar 

  • Boldrini M, Hen R, Arango V. Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression. Biol Psychiatry. 2012.

    Google Scholar 

  • Brusco A, López-Costa JJ, Tagliaferro P, Pecci SJ. Serotonergic ependymal fibres in rat and monkey: light and electron microscopic immunocytochemical study. Biocell. 1998;22:115–22.

    PubMed  Google Scholar 

  • Casanova MF, van Kooten IAJ, Switala AE, van Engeland H, Heinsen H, Steinbusch HWM, Schmitz C. Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autism patients. Clin Neurosci Res. 2006a;6(3–4):127–33.

    Article  Google Scholar 

  • Casanova MF, van Kooten IAJ, Switala AE, van Engeland H, Heinsen H, Steinbusch HWM, Hof PR, Trippe J, Stone J, Schmitz C. Minicolumnar abnormalities in autism. Acta Neruopathol. 2006b;112:287–303.

    Article  Google Scholar 

  • Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. J Am Med Assoc. 2003;290:337–44.

    Article  Google Scholar 

  • Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011a;1380:138–45.

    Article  PubMed  Google Scholar 

  • Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K. Neuron number and size in PFC of children with autism. J Am Med Assoc. 2011b;306:2001–10.

    Article  Google Scholar 

  • Devinsky O, Morrell MJ, Vogt BA. Contributions of ACC to behaviour. Brain. 1995;118(1):279–306.

    Article  PubMed  Google Scholar 

  • Dizeyi N, Bjartell A, Hedlund P, Taskén KA, Gadaleanu V, Abrahamsson PA. Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines. Eur Urol. 2005;47(6):895–900.

    Article  PubMed  Google Scholar 

  • Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, Tubaro C, Giambanco I. S100B’s double life: intracellular regulator and extracellular signal. Biochim Biophys Acta. 2009;1793:1008–22.

    Article  PubMed  Google Scholar 

  • Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry. 2002;52(8):805–10.

    Article  PubMed  Google Scholar 

  • Hof PR, Knabe R, Bovier P, Bouras C. Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol. 1991;82:321–6.

    Article  PubMed  Google Scholar 

  • Jacot-Descombes S, Uppal N, Wicinski B, Santos M, Schmeidler J, Giannakopoulos P, Heinsein H, Schmitz C, Hof PR. Decreased pyramidal neuron size in brodmann areas 44 and 45 in patients with autism. Acta Neuropathol. 2012;124:67–79.

    Article  PubMed  Google Scholar 

  • Kemper TL, Bauman M. Neuropathology of infantile autism. J Neuropath Exp Neur. 1998; 57(7):645–52.

    Article  PubMed  Google Scholar 

  • Kimelberg HK. Functions of mature mammalian astrocytes: a current view. Neuroscientist. 2010;16:79–106.

    Article  PubMed  Google Scholar 

  • Krabbe G, Matyash V, Pannasch U, Mamer L, Boddeke HW, Kettenmann H. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity. Brain Behav Immun. 2012;26:419–28.

    Article  PubMed  Google Scholar 

  • Laurence JA, Fatemi SH. Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects. Cerebellum. 2005;4(3):206–10.

    Article  PubMed  Google Scholar 

  • Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, Courchesne E, Everall IP. Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry. 2010;68(4):368–76.

    Article  PubMed  Google Scholar 

  • Morgan JT, Chana G, Abramson I, Semendeferi K, Courchesne E, Everall IP. Abnormal microglial-neuronal spatial organization in the dorsolateral prefrontal cortex in autism. Brain Res. 2012;1456:72–81.

    Article  PubMed  Google Scholar 

  • Oblak A, Gibbs TT, Blatt GJ. Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism. Autism Res. 2009;2(4):205–19.

    Article  PubMed  Google Scholar 

  • Raymond GV, Bauman ML, Kemper TL. Hippocampus in autism: a Golgi analysis. Acta Neuropathol. 1996;91(1):117–9.

    Article  PubMed  Google Scholar 

  • Sajdel-Sulkowska EM, Xu M, McGinnis W, Koibuchi N. Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders (ASD). Cerebellum. 2011;10(1):43–8.

    Article  PubMed  Google Scholar 

  • Santos M, Uppal N, Butti C, Wicinski B, Schmeidler J, Giannakopoulos P, Heinsen H, Schmitz C, Hof PR. Von Economo neurons in autism: a stereologic study of the frontoinsular cortex in children. Brain Res. 2011;1380:206–17.

    Article  PubMed  Google Scholar 

  • Schumann CM, Amaral DG. Stereological analysis of amygdala neuron number in autism. J Neurosci. 2006;26(29):7674–9.

    Article  PubMed  Google Scholar 

  • Simms ML, Kemper TL, Timbie CM, Bauman ML, Blatt GJ. The ACC in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups. Acta Neuropathol. 2009;118(5):673–84.

    Article  PubMed  Google Scholar 

  • van Kooten IA, Palmen SJ, von Cappeln P, Steinbusch HW, Korr H, Heinsen H, Hof PR, van Engeland H, Schmitz C. Neurons in the fusiform gyrus are fewer and smaller in autism. Brain. 2008;131:987–99.

    Article  PubMed  Google Scholar 

  • Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67–81.

    Article  PubMed  Google Scholar 

  • Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A, Chauhan V, Bobrowicz TW, de Leon M, Louis LA, Cohen IL, London E, Brown WT, Wisniewski T. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol. 2010;119(6):755–70.

    Article  PubMed  Google Scholar 

  • Whitaker-Azmitia PM. Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Int J Dev Neurosci. 2005;23(1):75–83.

    Article  PubMed  Google Scholar 

  • Whitaker-Azmitia PM, Wingate M, Borella A, Gerlai R, Roder J, Azmitia EC. Transgenic mice overexpressing the neurotrophic factor S-100 beta show neuronalcytoskeletal and behavioral signs of altered aging processes: implications forAlzheimer’s disease and Down’s syndrome. Brain Res. 1997;776:51–60.

    Article  PubMed  Google Scholar 

  • Zikopoulos B, Barbas H. Changes in prefrontal axons may disrupt the network in autism. J Neurosci. 2010;30(44):14595–609.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, New York University, 100 Washington Sq East, New York, NY, 11791, USA

    Efrain C. Azmitia

  2. Department of Biology, New York University, 10-09 Sliver Building, 100 Washington Square East, New York, NY, 10003, USA

    Allyson Impallomeni

Authors
  1. Efrain C. Azmitia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Allyson Impallomeni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Efrain C. Azmitia .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Azmitia, E.C., Impallomeni, A. (2014). Dynamic Brain Changes in Autism: Review of Telencephalic Structures. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_33

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-4787-0

  • Online ISBN: 978-1-4614-4788-7

  • eBook Packages: Behavioral Science

Publish with us

Policies and ethics

Search

Navigation