Excess neurons associated with autism
Children with autism have larger brains and more neurons for their age than is normal, results of a small preliminary study indicate.
Postmortem examinations from seven boys with autism revealed that they had 67% more neurons (1.94 billion) in the prefrontal cortex, an area of the brain that controls social and emotional development as well as communication, than six controls (1.16 billion, P=0.002), Eric Courchesne, PhD, of the University of California San Diego, and colleagues reported in the Journal of the American Medical Association.
On average autistic brains weighed 17.6% more than the normal average brain weight for age, data indicated.
Despite these observations, neuron counts in children with autism did not correlate to increases in brain weight that typically occur in children without the disorder.
If this were the case, the autistic children in this study would have experienced a mean 29.4% increase in brain weight instead of the 17.6% increase observed, according to the researchers. "Thus, the size of the autistic brain, overlarge though it is, might actually underestimate the pathology of excess neuron numbers,” they noted.
Although abnormal brain enlargement in children with autism was first documented about a decade ago, this is the first evidence that excess neurons, not other types of brain cells, may be responsible.
“Because neurons in all brain areas except the olfactory bulb and hippocampus are generated before birth, the present findings add significantly to mounting biological evidence that the developmental neuropathology of idiopathic autism begins before birth in some, possibly all cases,” Janet E. Lainhart, MD of the University of Utah in Salt Lake City, and Nicholas Lange, ScD, of the Harvard University Schools of Medicine and Public Health in Boston, wrote in an accompanying editorial.
Because of this, unchecked neuron proliferation may be due to dysregulation of the normal apoptotic mechanism that removes excess cortical neurons during the third trimester and early postnatal periods, the researchers hypothesized.
However, future studies may be challenging to conduct because these factors can only accurately be examined postmortem, and the numbers of tissue samples available from children with autism are small.
For this study, the researchers obtained brains from several tissue banks. Anatomists that were blinded to the presence or absence of autism diagnoses performed stereotactic cell counts for the entire dorsolateral and mesial portions of the prefrontal cortex.
All tissue samples were obtained from boys aged 2 to 16 years who died from 2000 to 2006, mostly due to hypoxia. One death occurred after a car crash, another from rhabdomyosarcoma and one from possible cardiac arrest.
The seven cases of autism included in the study ranged across the spectrum of disability, but none had Asperger's syndrome or pervasive development disorder-not otherwise specified.
The researchers found:
- Children with autism had neuron counts that were 79% higher in the dorsolateral prefrontal cortex than controls — 1.57 billion vs. 0.88 billion (P=0.003)
- In the mesial prefrontal cortex, neuron counts were 29% higher among children with autism than controls — 0.36 billion vs. 0.28 billion (P=0.009)
- Overall glia counts were similar between groups
- All observed differences in prefrontal cortex neuron counts between groups remained significant after controlling for age and time since death
“It will be important to include female cases in future studies, as etiological mechanisms may be discordant between sexes,” the researchers wrote.
They also noted that the study sample size was not large enough to establish behavioral links, and the small control group may not be representative of all healthy young children.Lainhart JE, Lange N. JAMA. 2011;306(18):2031-2032.