Cobbers on the Brain

Autism is a relatively newly recognized disorder that is quickly affecting more and more children as time progresses, affecting 1 in 68 today compared to just 1 in 150 in 2000. While much progress has been made in recent decades with the understanding of the mechanisms of autism, its cause is still widely misunderstood. There is no solid proof of the exact cause of autism, but it seems that individuals with susceptible genes are triggered by environmental toxins and deficiencies, leading to defects in neural signaling. Because environmental factors can trigger gene expression for autism, the preventions and treatments of autism are intriguing areas of study.

What is Autism?

Autism is a spectrum disorder, which means it has varying degrees of severity. All classifications of the autism spectrum involve difficulty socializing and communicating with others, and most cases involve repetitive behavior.

What Goes Wrong in the Brain?

• Increased number of neurons leading to oversized and overactive temporal and frontal lobes
• Ineffective elimination of unnecessary synapses
• Imbalance of excitatory and inhibitory neurotransmitters
• Heightened levels of immune cells in the brain
• Defective blood-brain barrier

How Do Toxicities Lead to Autism?

There are over 77,000 man-made toxins in our environment that were not meant to be taken in by humans. Toxins, whether they are pesticides, heavy metals, or plastics, must be removed from our bodies through innate mechanisms, or the biochemical processes in our bodies will go haywire. When an individual has a toxic overload, their body is depleting all of its amino acids in attempt to detoxify. Unfortunately, these depleted amino acids are necessary for normal brain function, and this inability to efficiently detoxify the body can lead to autism.

Most people understand that pesticides and fossil fuels are harmful to our health, but one overlooked toxicity is heavy metals. A lot of metals are essential to our body’s function, such as iron, but when any of them are too concentrated, problems arise. Specifically, high concentrations of copper in the body are very common in autistic individuals. Copper is an antagonist to zinc, which means they work together to make sure concentrations of each stay in check. When copper levels are too high, zinc is depleted. Low zinc levels have been correlated to autism because it leads to a dysfunctional immune system.

Does Gut Dysfunction Affect Immunity?

The answer to this question is yes. Scientists are now saying that at least 80% of our immune systems reside in our gut, and at least 90% of autoimmune diseases correlate with gut dysfunction. So fixing our guts will fix all of our health problems? Well, actually in most cases, yes. A compromised immune system is pointed to as one of the main factors in developing autism, and we just learned that 80% of our immunity lies within our gut. But first, lets learn how our guts became compromised in the first place.

“Leaky Gut” has been coined as the term describing increased intestinal permeability. It means that the large intestine is letting things through its walls that shouldn’t be leaking through. Bacterial cells can leak through the weak gut lining into the bloodstream, eventually into the brain where they can wreak havoc on neurons. Leaky gut can be caused by a variety of factors, including an imbalanced microbiome, poor diet, stress, and toxicities. Remarkably, repairing “leaky gut” in autistic individuals has been shown to dramatically decrease symptoms.

Can Autism Be Prevented or Cured?

It has been proven that a compromised immune system is correlated with the development of autism. Therefore, keeping an eye on a child’s immune function as it develops could be key in preventing autism. Three factors that have a negative effect on immune function are inflammation, nutrient deficiencies, and toxic overload. They can be addressed in a variety of ways:

• One of the most prominent causes of inflammation is leaky gut
  • To fix leaky gut, removing food allergens is a great place to start
  • Additionally, restore healthy gut bacteria with probiotics, and stay away from antibiotics
• Nutrient deficiencies can be tested for and supplemented until levels are healthy again
• Once inflammation and deficiencies are taken care of, the body has a much easier time detoxifying and reducing free radicals

Image 1: https://www.google.com/search?safe=off&biw=1280&bih=613&tbm=isch&sa=1&ei=0BS0W_zGBKa-jwSWhqnIBw&q=leaky+gut&oq=leaky+gut&gs_l=img.3..0i67j0l2j0i67j0l6.519207.520291..520406…0.0..0.199.908.6j3……1….1..gws-wiz-img.ujjU5nAd6Ms#imgrc=mOhjZuZTWzpH5M:

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What is autism? This is a very difficult question for people to answer for a variety of reasons. The biggest reason is because a wide spectrum of symptoms is experienced by individuals. This is because Autism Spectrum Disorders (ASD) are not caused by a specific gene mutation, but rather by a vast variety of environmental and genetic factors that all play a part in how the disease is presented in individual cases. Three of these factors will be discussed: Neural Connectivity, Mirror Neurons, and Excitation-Inhibition Imbalance. After discussing these factors, hopefully we will have a better understanding of what may lie as the root of the problem for ASD.

Neural Connectivity

In individuals’ brains with ASD, there is a significantly increased number of neurons. This is because there is a problem with ‘pruning’. In healthy brains, non-functional neurons are pruned away to give more room for working neurons to work and actually increase their power. This pruning process is done a lot with the mTOR pathway. This pathway enables apoptosis (cell death) and autophagy (cell absorption) to take place and effectively prune out the areas that are overgrown/unneeded. When the pruning does not take place, it leaves a crowded circuit causing lots of extra ‘noise’ causing the brain to function less efficiently. This is analogous to plants. Unhealthy branches are pruned off to give room for healthy ones to grow further and make the whole plant healthier.

Mirror Neurons

Do you ever wonder why you yawn when you see somebody else yawn? This is because of mirror neurons. Mirror neurons form connections that enable an individual to learn from its environment by imitation. In individuals’ brains with ASD, these mirror neurons are much less concentrated and possibly broken. This could possibly be the cause of those with ASD to have a lack of empathy for those around them. This could also cause lack of understanding of other individual’s movements and lead to the poor development of communication skills exhibited by many of those who suffer from ASD.

E/I Imbalance

There is a delicate balance in the brain called excitation and inhibition. Glutamate neurotransmitters are excitatory and GABA neurotransmitters are inhibitory. When working effectively, this balance gives the proper action potential to cells enabling them to fire or to rest. However, when this balance is not maintained only glutamate neurotransmitters can be activated. This causes excessive excitation in the cell. The glutamate then becomes excitotoxic and can kill cells, causing further damage to neurons and neural connections in the brain.

Closing 

Though we have just scratched the surface of the possible causes of ASD, this does help to give us an insight into what is happening in the brains of those around us that live with ASD. It’s important for us to try to understand these things as ASD is becoming more and more prevalent as 1 in 68 children today are diagnosed as being on the spectrum in some way, shape, or form, so we likely know someone living with ASD or we will know someone living with it in the future. As we know there is no real cure for ASD right now, but the first step to curing something is to understand what is going on and to identify the problem. Hopefully sometime soon we can start to put all of the pieces in place and figure out what is going on.

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With a rising frequency of affected individuals and increasing visibility in society, diving into the current knowledge of how autism affects the brain is important to inform us on how individuals with ASD’s (Autism Spectrum Disorders) experience the world from a different perspective. The following topics are of interest when considering autism’s cause and how the symptoms play out for individuals at any point on the spectrum. One of the most impactful and studied components of autism is the neuronal function/dysfunction that occurs in individuals with ASD’s.

Neural Connectivity and development:

In brains with autism, dysfunctional neural connectivity plays a large role in the manifestation of common symptoms seen in individuals with ASDs. Neurons are vital in passing chemical information from areas of the body to different areas of the brain. In brains of individuals with autism, these conversations between neurons are affected by an increased number of neurons and a lack of good communication between individual neurons. This concept can be understood by thinking about a 10-way phone conversation. With all ten individuals talking at once, it is impossible to pick out important bits of information and communicate the correct message to all the individuals! This is similar to the type of dysfunction seen in the neurons of brains with autism.

Another common developmental abnormality in brains with ASDs is the improper migration of neurons. This migration occurs before being born, and helps to place neurons where they need to be to function properly and align with each other. This has been connected to genetic mutations in the Reelin (RELN) gene that plays a huge role in the proper migration of neurons.

Genetic Mutations Contributing to Synaptic Malformation 

In nervous system, synapses are the gaps located between neurons which neurotransmitters and other molecules travel across to transmit signals to the next neuron in line. This process is vital to the proper communication between neurons, and outcomes in the cells. In individuals with ASDs, a common trait seen is malformed synapses between neurons. These malformations cause signaling, which is already at an increased level, to be inaccurate at transferring chemical information.

There are a few genetic mutations studied that play a role in the malformation of synapses in brains with ASD’s. This class of mutations has to do with the formation of Neurexin and Neuroligin, trans-membrane proteins tasked with physically docking the pre-synaptic (sending) neuron with the post-synaptic (receiving) neuron. Mutations causing deletions or mutated versions of these proteins negatively affect the ability of signals to reach the receiving neuron correctly.

These abnormalities play one piece in the puzzle of ASD’s, but is an important one to understand symptoms manifested in individuals with autism. Individuals with autism have symptoms related to complex malfunctions in the nervous system, immune system, and environmental stimuli that combine to create the experience of life with an autism spectrum disorder.

https://essenceofwellness.com/autismsupplementation/

Since the 1970’s the number of Autism Spectrum Disorder (ASD) diagnosis have greatly increased. This leaves people to wonder whether either the people have changed or if doctors have become more adept in classifying understanding ASD. In 2013 the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-5) reclassified not only the criteria for ASD but the disorder as a whole. Previously, there were five subdivisions of what we now consider ASD. Some scientists urge doctors not to hold the DSM-5 standards paramount, however, as the severity of ASD varies from individual to individual.  

Brain:

A large contributor to the variety of symptoms and there degree to which they are observed is the neurological component to ASD. It is well established that ASD is a neurological disorder but the exact cause remains unknown. Scientists have several theories, some having more evidence and weight than others, of mechanisms in the brain that may contribute or even in some way cause ASD. Several of these theories include:

Broken Mirror Theory

Mirror neurons are specialized neurons in the brain that are largely responsible for a phenomenon regarded as the Chameleon Effect. This effect states that humans tend to mimic or copy another individual. This can be seen most prevalently seen in yawning. These neurons are often responsible for reflected social behaviors and tend to be the cause of why you begin to take on the personality of the people who you spend the most time with. In ASD, it is observed that part of this pathway is missing and often gives rise to the impairments in social interactions. Mirror neurons are also sometimes linked with empathy and having malfunctioning cells could cause an inability to perceive the emotion of others, a symptom that is one of the pillars of ASD diagnosis.

Immune Response

Perhaps the most interesting theory to explain ASD and also the one with the most support. It is seen in some individuals with ASD that they have a weaker immune system and are more susceptible to disease. In addition to this, there appears to be a decrease of T-cells in the brain in patient with ASD. T-cells are the immune system cells that release a chemical signal called cytokines which are essential in regulating the immune response and inflammation. The lack of T-cell volume results in less cytokines, which is cause of the neural inflammation that is observed in ASD. There was one study that was conducted with laboratory mice and investigated the effect of an induced immune response to offspring that had ASD like behaviors. In this study, the mother was infected thirty days before conception and the offspring were observed that ASD like behavior symptoms. This is what gave scientists the biggest clue that immune response played a key role in the development of ASD.

Figure 1: This picture demonstrates the difference between normal and abnormal T-cell functioning in the brain. It is seen the more T-cells present, the higher the amount of cytokines which are important in the inflammatory response. When there are less cytokines microglia are activated and can be responsible for the abnormal brain function seen in ASD. https://www.moriahus.org/us/study-may-shed-light-on-autism-and-brain-inflammation/

Faulty Synapses

A second major player that scientists believe plays a role in ASD in the misfiring of neurons due in one way or another to faulty synapses. Synapses are the communication space between neurons. Researchers see synapses in ASD brains being altered in several ways but the main outcome is there tends to be overcrowding in the brain. The pathway the deals with removing neurons when they are no longer needed is inhibited and causes a high concentration of neurons in the brain. The neurons cannot communicate effectively with each due to the there being too many. In ASD this can be seen with being overstimulated, there are just too many neurons in one area all firing at once it overwhelms the individual.

Figure 2:  A drawing of an ASD brain (right) and normal brain (left) shows the increased amount of connections observed in patients in ASD which leads to overstimulation of the brain and gives an overwhelmed feeling in response. http://newscenter.sdsu.edu/sdsu_newscenter/news_story.aspx?sid=73005

There is also an altered shape and orientation of the synapse, which causes the neurons to be unable to properly send messages. Sometimes this is seen in ASD being the cause of unable to response in the normal way to events.

Behavior:

Of course understanding the brain is important when thinking about ASD but there is another component that may be overlooked when thinking about the disorder (hint: read the header of the section). Behavior is the ongoing result of the differences in the brain compared to the normal brain. Those with ASD have altered behavior, that has been clear since it was first discovered. Many of the behaviors that are associated with ASD are only detected in childhood while several continue to be present throughout life. Social isolation and loss of language skills are the two most prevalent throughout life. After the initial diagnosis, an individual can also be placed into categories which classify the severity of ASD.

Average to Severe ASD

As stated above, the two most common ways to identify ASD are delays in language development coupled with social impairments. ASD is typically arranged into three different levels, titled one to three. One states that an individual requires support and have noticeable social impairments as well as inflexible behavior. Many of the behaviors below are often exhibited with this level but not to the degree that is observed in others. Level two, “requires substantial support”, usually some language can be observed in this stage but tends to be limited. Social issues are more prevalent, as most communication is nonverbal, with difficulty coping with change, and inability to focus which often manifests in ADD or ADHD. The third level is most severe, not exchanging rarely any words if ever speaking. This makes social situations even more difficult and is marked occasionally by aggressive behavior. The behavior issues that are observed at the previous two levels are also seen here but at higher degrees.

Figure 3: Several disorders and symptoms surround ASD and overlap with each other to give rise to the behavior that is commonly seen. http://www.adoptontario.ca/autism

High Functioning ASD or “Aspergers”

Although there is not a DSM-5 diagnostic criteria for Aspergers anymore, the term is still used frequently today often to describe high functioning cases. The main difference between what people considers Aspergers and average ASD is there is language develops normally in an individual with Aspergers. The symptoms presented tend to be more mild as well. The social component of ASD is what is most commonly reflected in Aspergers because someone with this variation of the disorder could want to make friends but be unsure of how to do so. Social awkwardness very common. It is not the lack of empathy that categorizes Aspergers but rather being incapable of processing the emotion that the other person is feeling. As seen in the figure above, individuals with Aspergers often display many of the behavioral effects that are seen with ASD. Most prevalent are OCD, ADHD, ADD, repetitive behaviors, anxiety, and even more listed above. The degree to which they are experienced however is what varies from case to case. There is no one way put ASD or Asperger’s into a box and that is why is it essential to understand the link between the mechanisms in the brain and what is seen by the public.

The Link Between the Two

When looking at disorders such as ASD is important to note both the underlying cause as well as the behaviors that are exhibited for everyone to see. Brain and behavior are connected on the most basic level, one giving rise to another, and the understanding of both together is what leads to the acceptance. Research for both fields brings to light more ways to understand individuals with ASD and provide possible treatment, whether it be therapy or medicine based. ASD is a complex disorder to say the least but through learning more, the world as a community not only becomes more educated about causes of disorders but accepting toward those who are affected.

http://www.autism-society.org/living-with-autism/autism-and-your-family/

http://2018neurochem.pbworks.com/w/page/128912631/Advances%20in%20understanding%20the%20pathophysiology%20of%20autism%20spectrum%20disorders