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. 2011 Nov 9;306(18):2001-10.
doi: 10.1001/jama.2011.1638.

Neuron number and size in prefrontal cortex of children with autism

Eric Courchesne  1 , Peter R Mouton, Michael E Calhoun, Katerina Semendeferi, Clelia Ahrens-Barbeau, Melodie J Hallet, Cynthia Carter Barnes, Karen Pierce
Affiliations

Neuron number and size in prefrontal cortex of children with autism

Eric Courchesne et al. JAMA. .

Abstract

Context: Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.

Objective: To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006.

Main outcome measures: Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed.

Results: Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children.

Conclusion: In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.

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Comment in

  • Increased neuron number and head size in autism.
    Lainhart JE, Lange N. Lainhart JE, et al. JAMA. 2011 Nov 9;306(18):2031-2. doi: 10.1001/jama.2011.1633. JAMA. 2011. PMID: 22068999 No abstract available.
  • Neuron number in children with autism.
    Anghelescu I, Dettling M. Anghelescu I, et al. JAMA. 2012 Feb 22;307(8):783; author reply 783-4. doi: 10.1001/jama.2012.191. JAMA. 2012. PMID: 22357826 No abstract available.
  • Organization in autism.
    Kana R, Percy A. Kana R, et al. Arch Neurol. 2012 Jul;69(7):906-7. doi: 10.1001/archneurol.2011.3596. Arch Neurol. 2012. PMID: 22409936 No abstract available.

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