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Akshara R

Pathophysiology of Autism

Autism is a condition which affects an individual’s communication, behavioural skills as well as learning abilities. Since there are multiple conditions of autism ranging in various degrees of severity, the broad spectrum of disorders is often referred to as autism spectrum disorder (ASD).

So, what are the pathological and physiological changes in the brain of an autistic individual? We can cover a few of the important ones to get a better insight into this condition.

  1. Neuropathology


Many postmortem and imaging studies showed that there were abnormalities in the structures of the cortex, amygdala, hippocampus and cerebellum. It was also reported that medial nuclei of the amygdala, septal nuclei and a part of the cortex have more densely packed neurons compared to healthy cells. Focal cortical dysplasia (FCD) which refers to a heterogeneous group of lesions was also observed in these individuals. Due to FCD, there was abnormal migration of daughter neuron cells to their target regions. Another study also found that cell density was also higher particularly in the hippocampus region in autistic individuals.

An interesting fact is that many studies have also shown that autistic individuals have a larger brain compared to normal individuals.



  1. Genetic causes


There have not been many breakthroughs in finding the genes associated with ASD. Although not too long ago an important identification was made concerning the gene associated with Rett syndrome. Rett syndrome is a rare genetic disorder where there is a progressive loss of motor skills and language due to abnormalities in the development of the brain.


The genetic defect seen in Rett syndrome is that there is decreased expression of methyl CpG binding protein 2 gene. Because the gene responsible for the regulation of methylation of other genes itself is mutated, autism-associated genes could also have methylation errors.

Another major mutation was observed in Fragile X gene FMR1. Reduced expression of this gene causes mental retardation which is a condition seen in autistic patients.


Are male children more prone to being autistic than female children?


The answer is yes, the ratio of male to female ASD individuals is reportedly 1:4. Although the exact causes are not known there are many speculations.

Some studies reported that there may be some epigenetic changes in the sex-specific effects of Y-linked genes combined with some mutations in the X-linked gene as well due to which there is a higher expression of some genes in the Y chromosome. Genetic mutations could be brought about by hormones or hereditary factors but sometimes external entities like high-stress environments, drugs and infections could also increase the chances of causing mutations in certain autism-related genes.


  1. Associations between the immune system and the brain.


The peripheral immune system is said to have several abnormalities. This confirmed several studies which showed that there were abnormalities in the activation of microglial cells and the innate neuroimmune system. Due to neurological inflammation and immune dysregulation commonly seen in ASD individuals, the blood-brain-barrier function is also altered.


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