Brain Hyperplasia in Autism

by Dr. Kenneth Alibek 

Autism is most often diagnosed to 2-3 years of life. At this time, studies show that the brain size of children with autism is increased. This confirms that the increase in brain size begins much earlier, perhaps before the appearance of clearly noticeable behavioral symptoms.

It is known that in some children with autism, there is hyperplasia of some lobes of the brain, which can be 30% larger in volume than in healthy children. Metabolic, functional, behavioral and histological studies show that the structure of the brain can be altered in autism.

For instance, a significant increase in the cerebral cortex and white matter volumes of the brain in autistic children aged 2 to 3 years and a slow rate of change in volume later in life was found.


As well, it was tested whether these volume anomalies are limited to specific cerebral areas or whether they are spread throughout the brain. Using magnetic resonance imaging (MRI) to quantify the volume of the brain lobes (frontal, temporal, parietal and occipital regions) using classical boundaries. 

In some regions, there were signs of gray matter and white matter hyperplasia in patients aged 2 to 3 years (an increase of up to 20%), but there appeared to be an anterior or posterior gradient in the degree of hyperplasia. The frontal lobe showed the largest increase, while the occipital lobe differed slightly from the normal one. In older children, differences between gray and white matter were not found. 

By examining the relationship between regional volumes and subject age, it was found that frontal, temporal, and parietal volumes of white matter, as well as frontal and temporal volumes of gray matter, changed significantly more slowly in patients with autism than in the control group. For example, the volume of white matter in the frontal lobe increased by about 45% from 2-4 years to 9-11. 5 years in healthy children, and only 13% in patients with autism. 

In addition, increased expression of IL-6, TNF-α, MCP-1, TGF-β1, IFN-γ, IL-8, and other immune response-related genes has been reported in these brain regions and in cerebrospinal fluid.

Astrogliosis and microglia activation, along with increased cytokine expression in different regions in the autistic brain at different ages shows that patients with ASD during life observed altered the neuroinflammatory response. Patients with ASD have increased Astro-and microgliosis in the cortex and cerebellum.

A 2016 study fully confirms the role of inflammation in autism, showing that at least 69% of children with the disorder had neuroinflammation and microglia activation. Several other authors also have shown that the enlargement of many areas of the brain characteristic of children with autism is not actually excessive growth, but rather brain edema (encephalitis) as a result of constant neuroinflammation.

The increase in brain volume in the early period of development is explained by proliferative and hypertrophic astrocytes, while the decrease in brain volume by the time the first autistic symptoms appear can be explained by the death of neurons as a result of prolonged inflammation.

Rossignol and Frye (2014) examined publications showing signs of inflammation in the brains of children with ASD published between 2005 and 2013. These studies have shown that children with ASD have:

  • activation of microglia and astroglia in the middle frontal gyrus

  • anterior cingulate gyrus and cerebellum 

  • elevated levels of tumor growth factor anti-inflammatory cytokines-1 and protein-1 chemoattractant proinflammatory macrophages

  • increased levels of IFN-gamma, MCP-1, TGF-beta2, and IL-8 in cerebrospinal fluid (CSF)

  • decreased quinolic acid and neopterin

  • increased biopterin levels in CSF 

  • increased TNF-alpha levels in CSF

  • increased expression of certain immunogenic genes in the superior temporal gyrus 

  • reactive gliosis in BA22, BA44, and BA39 

  • increased proinflammatory cytokines in the frontal cortex 

  • increased expression of NF-kappaB in the orbitofrontal cortex 

  • increased concentrations of 3-chlorothyrosine in the cerebellum and temporal cortex

A study of the brain tissue of a child with autism and its comparison with the control showed that the child with autism cell proliferation in the brain is much higher than in the control.

All these results once again confirm the role of inflammation in autism. 


Townsend, J., Westerfield, M., Leaver, E., Makeig, S., Jung, T.-P., Pierce, K., & Courchesne, E. (2001). Event-related brain response abnormalities in autism: evidence for impaired cerebello-frontal spatial attention networks. Cognitive Brain Research, 11(1), 127–145. doi:10.1016/s0926-6410(00)00072-0

Depino, A. M. (2013). Peripheral and central inflammation in autism spectrum disorders. Molecular and Cellular Neuroscience, 53, 69–76. doi:10.1016/j.mcn.2012.10.003

Kern, J. K., Geier, D. A., Sykes, L. K., & Geier, M. R. (2016). Relevance of Neuroinflammation and Encephalitis in Autism. Frontiers in Cellular Neuroscience, 9. doi:10.3389/fncel.2015.00519

Rossignol, D. A., & Frye, R. E. (2011). A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Molecular Psychiatry, 17(4), 389–401. doi:10.1038/mp.2011.165 

Rossignol, D. A., & Frye, R. E. (2014). Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Frontiers in Physiology, 5. doi:10.3389/fphys.2014.00150

Pearson, B. L., Corley, M. J., Vasconcellos, A., Blanchard, D. C., & Blanchard, R. J. (2013). Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles. Behavioural Brain Research, 243, 138–145. doi:10.1016/j.bbr.2012.12.062

Kaushik, G., & Zarbalis, K. S. (2016). Prenatal Neurogenesis in Autism Spectrum Disorders. Frontiers in Chemistry, 4. doi:10.3389/fchem.2016.00012

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