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The Pathophysiology of Autism Unpacked

September 29, 2023

When we consider the pathophysiology of autism, there is a lot of information to process. As a background, think about the fact our bodies function like an integrated system where each part and subpart plays a vital role in its overall functioning. When one part is affected, it may destabilize the system leading to disruptions in other interrelated systems. 

The Pathophysiology of Autism Unpacked

Your physiology is your entire system that works together to ensure that all functions from the cellular level to the functioning of the organs and tissues work at optimal level. The term physiology is defined as the study of how the human body works together.

When this system is affected in a specific area and causes other systems to falter, this can lead to the development of diseases or disorders that we observe. This disrupted system describes pathophysiology. Pathophysiology is the term given to describe an abnormal physiology linked to certain diseases or conditions. 

In this article we will dive into research and uncover what science deems as the causes of autism symptoms from a physiological level. We will look into the physiological processes that are possibly linked to some autism related symptoms. Studying the pathophysiology of autism can be a stepping stone to understanding autism, and how best individuals or children with autism spectrum disorder (ASD) can make sense of their traits from a scientific level.

Breaking down the pathophysiology of autism

As we know, autism spectrum disorder is characterized by difficulties with social interaction and communication, as well as restricted or repetitive behaviors. Some symptoms also include sensory sensitivities, inflexibility etc. Scientists have sought to find out what the causes of ASD are from a physiological point of view—what physiological abnormality is responsible for the observed symptoms of children with ASD? Let’s break it down.

1. Dysfunction of neural functions

Some findings on the pathophysiology of autism are based on the brain’s ability to perform neural functions efficiently. Our brain’s neural function is best assessed based on its ability to build healthy neural circuits, and this is granted by a process called synaptic pruning. A synapse is the point on a nerve that transmits information from one neuron to the next. A synapse allows for neural communication between cells. When there’s too many synaptic connections, the brain goes through a process of cutting down; known as synaptic pruning.

To understand what synaptic pruning is, here is an analogy:

Suppose you’re doing a group project, and you and your group members need to collect more data for this project. So what then happens is that your group sets out to seek candidates, and winds up with say 100 potential candidates suitable to take part in the project. 

Your team brings the candidates together in one room, but even though the 100 candidates are suitable, your team soon realizes that there are far too many, and you need to select only the most relevant candidates. Through a process of reevaluation, and some testing, you select your top contenders for the project. The result of this is being left with 30 top participants that will strengthen the outcome of your project.

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So, let’s bring this analogy to synaptic pruning; at infancy, a child is born with existing synaptic connections between neurons (your team/group members), as the infant grows and develops, there’s an explosion of synaptic formations that occurs called synaptogenesis (the stage where you wind up with 100 potential candidates). This stage of synaptogenesis is important because it is the stage where learning takes place, memory formation occurs etc., at this stage, the brain is gaining all this knowledge and collecting all this data (the stage of reevaluating your 100 candidates). 

However, after a while, the brain decides, okay this is a lot of information, and so it begins to cut out the bits that are least important and only selects the key information that the infant needs during his/her development. So the brain keeps what it needs, and loses or discards what it doesn’t need (like the analogy, this is the stage where you gather all the information from your 100 potential candidates; and the final 30 represent the key candidates that will be most useful towards your project). This stage is known as synaptic pruning (cutting out the unnecessary information to sustain the key information).

Synaptogenesis typically starts at infancy and by the age of two to three (early childhood or toddler), synapses are at a peak and thereafter synaptic pruning takes place. Since autism is characterized by underlining neural connectivity difficulties, some reviews resolve that neurocognitive studies could explain the pathophysiology of autism.

Scientific review of neural dysfunction

The review by Yenkoyan, et al. (2017) provides an overview of research of the pathophysiology of ASD based on modern neurocognitive findings. The areas highlighted include “impairments in neural connectivity, neural migration, imbalance in excitatory-inhibitory neural activity, damaged synaptogenesis and dendritic morphogenesis, disturbances in neuro-immunity, and broken neuron theory”; all of which inform successful brain development.

Studies in neural density have found a higher number of neurons among autistic individuals which makes the process of synaptic pruning more challenging. The fine tuning of neurons also helps with lateralization (a process of the brain that specializes some neural function to one side of the brain), which is important for good language function.

Theory of mind and the broken mirror theory

To explain the difficulties with social interaction and cognition that some autistic children or individuals experience from a neurocognitive perspective, the broken mirror theory of autism was developed. This theory is derived from nerve cells called mirror neurons. Mirror neurons are typically involved in the understanding action and imitation of other individuals

For typically developing individuals, when one observes an action being performed, certain neurons that code for the same action are activated in the observer’s motor system; mirroring the performer’s action. The brain’s ability to mirror this is important because the observer is able to understand the action independently. An example of a mirror action is yawning—usually when someone yawns, it causes the observer to also yawn. 

In line with the mirror theory, is the theory of mind. The theory of mind refers to the ability to understand others, understand subjective thought processes and make inferences of the feelings or mental states of others.

From research studies, it is found that some autistic children have difficulties with mirroring behavior, and some aspects encompassing the theory of mind. These traits affect the social interaction and cognition difficulties that some autistic individuals experience.

Excitatory/inhibitory imbalance

Other factors encompassing neural dysfunctions include the excitatory, and inhibitory imbalance at synaptic receptors that is essential for brain function such as sensory processing and cognitive processes. Certain receptors are important for regulating the excitation and inhibition of some neurotransmitters in the brain that are important in cognitive and sensory processing. 

Neurotransmitters are chemical substances released at the synapse by a nerve impulse that transfers information to the next target cell. If there’s insufficient neurotransmitters, the message will not be successfully transmitted, or if there’s too much, it will cause an overexcitation in the next cell (target cell). Hence the regulation of these receptors that release and receive the neurotransmitters are important. 

2. Genetic and epigenetics factors in autism

Epigenetics is the study of how the environment and our behaviors affect how our genes work. Although epigenetic changes are reversible, and do not change your DNA sequence, they can however change your body reads a DNA sequence. In addition, some epigenetic changes can be hereditary. 

Your DNA sequence is considered the template of your body’s makeup. The coding of the DNA sequence is vital to the overall function of the cell. An epigenetic change is one that causes modification to DNA that regulates whether genes are turned off or on. An epigenetic change therefore impacts the production of certain proteins in the cell that are necessary for cellular functioning.

An analogy for contextual understanding is as follows: your house represents the DNA sequence, and there are light switches in every room. A genetic change is one that completely changes the shape or form of your house, while an epigenetic change does not modify the house but impacts the routine of how you care for your home. 

Most people develop the habit of turning lights off in rooms that don’t need to be lit. So if there’s no need for lights in a room, the lights are meant to be off, or having lights off when they should be on. So then an epigenetic change is like an infant going into a room and turning on the switch when it is meant to be off, or conversely turning it off when it is meant to be on.

Rett’s syndrome

The study of genes has been instrumental in uncovering the pathophysiology of autism. A gene mutation known as Rett’s syndrome has been found through these studies. Genetically, Rett’s syndrome is caused by a gene mutation at the X chromosome on a gene called MECP2, but mutation can occur at any loci. It’s been discovered that this rare mutation affects brain development almost exclusively in girls.

Rett’s syndrome affects several areas encompassing the child’s lifestyle; some of these include: the rapid loss of coordination, loss of speech, and loss of the coordinated use of the hands. Of the symptoms of Rett’s syndrome, the main feature of this condition is constant repetitive hand movements. 

The syndrome can be seen between the age of six to 18 months with observable developmental milestone regression of abilities the child had previously gained. Unfortunately there’s no cure for Rett’s syndrome but through physiotherapy, speech therapy, and nutritional support, the child can better manage the symptoms to improve his/her quality of life.

The symptoms of Rett’s syndrome are similar to some symptoms of ASD. Therefore, studying the genetic defects in Rett’s syndrome could offer some answers for autism related symptoms.

Closing on epigenetics

Although some scientists have found genetic anomalies linked to autism, it hasn’t been narrowed down to one causality due to the heterogeneity of autism symptoms. However, an overview of research indicates that instead of studying to find a single gene that codes for autism traits, scientists have instead turned to looking for similarities in functions of genes which are mostly associated with single gene disorders with altered expression that cause the autism symptom. 

In other words, what this means is that suppose a specific gene for an ASD trait is found; scientists are seeking to find the common denominator in the parts that encompass that gene to study the altered function that causes the autism symptom.

3. The endocrine system

The endocrine system consists of glands that secrete hormones, namely: the thyroid gland, the parathyroid glands, the hypothalamus, pituitary gland, and pineal gland in the brain, the thymus, the pancreas, ovaries (in women), and testes (in men), and the adrenals. 

Of these glands, the thyroid gland is the one that is most prominent in fetal development. Some research studies suggest dysfunction in the thyroid gland can be the cause of ASD symptoms. This is because secretion by the thyroid regulates the fetal gestation, especially within the first trimester; especially for placental development. The direct effects of thyroid dysfunction still need to be unpacked further to determine whether the mechanisms behind the dysfunction can offer some answers as to the susceptibility of developing autism.

In summary

The physiology of the human body is complex, offering a wealth of possibilities to explain the causes of the pathologies that lead to disorders, conditions, or diseases.

In terms of the pathophysiology of autism, research points to factors such as the actions of environmental and endocrine risk factors, genetic factors, the maternal immune system, inflammation, and so many other factors. 

From a scientific and medical point of view, it is important to uncover the various risk factors that work cooperatively in some form or another to influence neural development to better understand the causes of autism symptoms. The road to this discovery is not linear, it takes a lot of trial and error to reach to any single conclusion, even then, it may unlock several other mysteries—this is the beauty of human physiology.

Regardless of what research shows, autism offers so many unique and positive qualities; from savantism, to unique traits that make autistic individuals superheroes with talents that surpass human understanding. While science is great and offers opportunities to make the lifestyles of autistic individuals easier in terms of coping in a “neurotypical world”, we must never forget to celebrate that every individual with autism is unique. How much more incredible is it to think that amongst the billions of people in the world, there are no two individuals who are exactly the same as each other.


Ramachandran, V. S., & Oberman, L. M. (2006). Broken mirrors: a theory of autism. Scientific American, 295(5), 62–69. https://doi.org/10.1038/scientificamerican1106-62 

Samsam, M., Ahangari, R., & Naser, S. A. (2014). Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance. World journal of gastroenterology, 20(29), 9942–9951. https://doi.org/10.3748/wjg.v20.i29.9942

Yates, L., & Hobson, H. (2020). Continuing to look in the mirror: A review of neuroscientific evidence for the broken mirror hypothesis, EP-M model and STORM model of autism spectrum conditions. Autism, 24(8), 1945–1959. https://doi.org/10.1177/1362361320936945 

Wilson, H. A., Creighton, C., Scharfman, H., Choleris, E., & MacLusky, N. J. (2020). Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder. The Neuroscientist. https://doi.org/10.1177/1073858420952046

Yenkoyan, K., Grigoryan, A., Fereshetyan, K., & Yepremyan, D. (2017). Advances in understanding the pathophysiology of autism spectrum disorders. Behavioural brain research, 331, 92–101. https://doi.org/10.1016/j.bbr.2017.04.038



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