Excess Neurons Found in Autistic Brains, Evidence of In Utero Origin of Condition
Still in hopes of finding the key to how autism spectrum disorders develop in children, researchers have now found that autistic children have significantly more nerve cells in the part of the brain known as the prefrontal cortex, which is involved in communication, social skills and language. The findings, published in the Journal of the American Medical Association (JAMA), indicate that autism originates prior to birth in these cases.
Lead researcher Eric Courchesne PhD of the University of California, San Diego, studied the brains of seven autistic boys between the ages of 2 and 16 after their deaths. He compared his analysis to the brains of six unaffected boys who died at similar ages. The autistic donors had all died between 2000 and 2006 from various causes including hypoxia, car accident, and possible cardiac arrest. The cases fell across the spectrum of disability, but none had Asperger’s syndrome or Pervasive Development Disorder-NOS.
The experts who performed the autopsies were blinded to diagnosis. They also conducted unbiased sterotactic cell counts, rather than just estimating neuron counts from density in small blocks.
The boys with autism had about 67% more nerve cells in their prefrontal cortex, a part of the frontal lobe of the brain. This part of the brain is further divided into three sections, the dorsolateral, orbitofrontal, and the mesial prefrontal areas. When taken separately, neuron count for the children with autism were 79% higher in the dorsolateral region and 29% higher in the mesial prefrontal cortex. Other cell types, such as glial cells, were similar in both affected and unaffected brains.
The brain itself also weighed 17.6% above normal for age in the autistic children.
While some might mistakenly believe that bigger brains and more nerve tissue would be an indication of increased ability, Dr. Courchesne explains that an overabundance of neurons probably leads to difficulty in their ability to connect and communicate with each other. That leads to pathways that slow down or prevent normal interaction between different regions of the brain. Learning and memory, for example, requires the interaction of nerve cells between the prefrontal cortex and the hippocampus.
So when and why does the excess brain tissue form? Dr. Courchesne notes that more research definitely needs to be done, but thinks that unchecked proliferation or a failure of the normal process of neuronal pruning through apoptosis in the third trimester and early postnatal period may be occurring.
A separate, unrelated study notes that the neurons in the prefrontal regions of autistic brains show altered methylation patterns which suggest genetic factors are likely involved. Dr. Zhiping Weng, PhD, of the University of Massachusetts Medical School in Worcester, Mass., and colleagues studied 16 autistic individuals (both children and adults) and found trimethylated forms of the H3K4 demethylase (H3K4me3) were “extraordinarily common.”
Previous studies suggest that an alteration in H3K4, a molecule that helps to form the backbone of DNA, is involved in autism spectrum disorders. "Generalized disruption" of the H3K4me3 landscape normally changes during infancy as neuronal development progresses.
“Knowing that we have a specific type of defect that occurs very early in development really helps us to focus and sharpen the next steps in research to determine what caused the excess,” says Dr. Courchesne.
Courchesne E, et al "Neuron number and size in prefrontal cortex of children with autism" JAMA2011; 306(18): 2001-2010.
Lainhart JE, Lange N "Increased neuron number and head size in autism" JAMA 2011; 306(18): 2031-2032.
Shulha H, et al "Epigenetic signatures of autism: Trimethylated H3K4 landscapes in prefrontal neurons" Arch Gen Psychiatry 2011; DOI: 10.1001/archgenpsychiatry.2011.151.
Note: The UCSD study was supported by Autism Speaks, Cure Autism Now, The Peter Emch Family Foundation, the Simons Foundation, The Thursday Club Juniors, and the University of California San Diego-National Institutes of Health Autism Center of Excellence, and by a grant from the National Institute of Mental Health. The UM study was funded by Autism Speaks, the International Mental Health Research Organization, the National Alliance for Research on Schizophrenia and Depression, the National Institutes of Health, and the National Science Foundation.