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The Complexity of Autistic Spectrum Disorder

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Recently in class discussions we had the chance to look at Autism Spectrum Disorders (ASD). ASD currently affects roughly 1 in 68 children. ASD shows abnormalities in social behavior. While I was growing up, I was fortunate enough to get to know two kids with ASD. The two kids were both in my grade and each of the showed a skill that they exceeded in. One of the kids would take sports statistics and memorize them. His brain loved numbers, but only numbers specific to sports. If I had asked him a certain score of a game played in 1990 between the Minnesota Vikings and Green Bay Packer, he would have told me right on the spot. The other kid was a walking calculator. He knew any math problem laid in front of him.

As these skills continued to progress, the two kids’ social behaviors drastically continued to decrease. Social interactions and communication started to become exceedingly difficult and that is when I found out they had ASD. Both kids also shared a rare diagnosis of savant’s syndrome as well. Savants syndrome basically sums up to be where one area of your brain shows extreme supremacy over others. This would explain the rare skills that both these kids showed. In most cases, savant patients also have ASD. After reading our class discussion, it started to make sense to me on how this might come to be. One of the theories discussed in the development of ASD is neural connectivity. In autism, patients undergo an overabundant number of neurons. This overabundance disables connections between the brain interactions. So, we ultimately get cut off connections which impair the brain in certain areas down the way, but in some cases these neurons may drastically increase the capability of the portion of the brain they are stuck in. This would perhaps explain savant syndrome.

There are many other theories that tie into the development of ASD with one of them being the impairment of synaptogenesis. This theory explains how in early life, our brain has a lot of synapse formation and with synaptogenesis, the removal of certain synapses takes place. This process is important in the fact that synapses are being taken out and they are the correct ones. In ASD this process is impaired, and the consequences would be brain underdevelopment leading to dysfunctional behaviors.

Although both theories make sense, I like to focus on neural connectivity. Again, bringing it back to my experience and relating savant syndrome to autism, I feel neural connectivity is the main issue. In savants I now can picture their brain. In my artstract below you can see an outline of what I feel is going on. In a human brain connection are supposed to connect the dots. These connections are supposed to be smooth and transfer from one to another without issues. In a ASD or savant syndrome brain we see that only a few of the dots are connected before there is a barrier where you cannot get to the next dot. In my experience, the portion of the brain that was controlling numbers was the dot that was connected, but then there became a barrier when trying to connect to the social interaction dot.

Of course, ASD is a lot more complicated then connecting dots but it is a graphic that helps me. In my experience with ASD  I never had the chance to see others. In the cases where I knew the individual I thought their behavior was normal for ASD. However, they also had the rare diagnosis of Savants as well. Learning about ASD more in depth and the complexity of the disease has opened my eyes to the severity that ASD holds.

Disease/Health

Polycystic Ovarian Syndrome (PCOS) and Obesity: A “Chicken or the Egg” Paradox

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What is PCOS?

Polycystic Ovarian Syndrome (PCOS) is a condition in which the ovaries produces excessive amounts of androgens, the male sex hormone. Excess of the male sex hormone in women disrupts the fragile balance that is maintained between estrogen, progesterone, and the androgens. This hormonal imbalance often results in the development of cysts within the ovaries, contributing to irregular menstrual cycles, infertility, and anxiety/depression. Additionally, overproduction of these androgens leads to excess hair all over the body, acne, and insulin resistance and obesity.

Studies have concluded that women affected by obesity have a greater risk for PCOS and women diagnosed with PCOS have an increased risk for obesity.

Obesity as Risk Factor for PCOS

The majority of women with PCOS are obese or overweight and/or have insulin resistance (50-90%). Resistance to insulin is a primary driving factor for obesity and type 2 diabetes, as insulin is a key regulator in maintaining normal blood sugar levels. An emerging theory of the cause of insulin resistance can be seen in studies of the hypothalamus, a structure of the brain responsible for regulating appetite, hormone release, and many other key metabolic roles. When there is inflammation occurring in the hypothalamus, however, there is disruption to many of these metabolic pathways that are vital for normal insulin signaling. This inflammation within the hypothalamus is prompted by a high-fat diet, further emphasizing the importance of a healthy diet in the maintenance of effective peripheral and neurological functioning.

Insulin resistance in peripheral tissues was actually found to enhance steroidogenesis in the ovaries, leading to higher production and consequent levels of androgens. This feature results in the hormone imbalance that contributes to many of the symptoms of PCOS. 

PCOS as Risk Factor for Obesity

On the other side of the paradox, elevated androgen levelsin women with PCOS have been shown to impair insulin signaling, contributing to insulin resistance. As demonstrated above, insulin resistance promotes androgen production. As androgen elevations promote insulin resistance, the positive feedback mechanism present between PCOS and obesity can clearly be seen. 

As indicated in the figure, there are a number of additional overlapping factors that perpetuate this sort of positive feedback mechanism that can be found between PCOS and obesity within patients.

Clinical Implications

Since PCOS and obesity undoubtedly compound the effects of the other, it is necessary to develop novel, effective treatments that will target both conditions. A strategy that has been used for a while to combat PCOS symptoms and infertility is hormonal oral contraception. This form of contraception provides supplemental estrogen and progesterone, thereby attempting to restore hormonal balance and allow for normal ovarian function. Additionally, antiandrogens have been reported to be effective in both lowering androgen levels improving insulin sensitivity. These drug strategies hold great potential for effective treatment of those who struggle with both PCOS and obesity. 

Promotion of exercise and a healthy diet in those with PCOS is important in the clinical setting, as these strategies help to both undermine the severity of PCOS symptoms and combat the effects of obesity. However, this feat is easier said than done, as many women with PCOS also struggle with anxiety or depression that may hinder efforts to stay active and eat well. 

It is ultimately necessary to increase research about PCOS and obesity so that more effective treatments emerge in the hopes of minimizing the difficulties that each condition brings about. 

 

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To go or not to go: how excitatory/inhibitory imbalances can shape ASD

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Hello everyone! Today I’d like to talk a little bit about some factors that influence the development of Autism Spectrum Disorders (ASD), specifically how maternal infection/stress can increase the risk of ASD.

ASD is a spectrum of neurodevelopmental disorders that affects 1/58 children in the United States.  The key symptoms of ASD, which can range widely in severity, are impaired social interactions, problems with language/communication, and repetitive behaviors.

A lifelong condition, the cause of ASD is not yet known, although strides are being made to identify risk factors and molecular mechanisms that cause ASD.  Changes in the typical balance between neurons that stimulate other neurons (excitatory: Glutamate) and those that inhibitory other neurons (GABA) represent a key process that may explain ASD.

GLUTAMATE & GABA:

Picture two different neurons—If you’d like you can even color-code them in your head, one green one red. The green neuron produces and uses a neurotransmitter called glutamate to communicate with the other neurons it talks to, while the red neuron uses GABA.

When the green neuron is activated, glutamate is released into the synapse. Glutamate then binds to its receptor on the post-synaptic membrane and ultimately opens up a sodium channel. Positively charged sodium (highly concentrated outside the cell) rushes inside the post-synaptic neuron and makes that neuron more likely to fire, hence glutamate is excitatory. Cool!

Conversely, the red neuron does all the same steps, just swap out glutamate for GABA and chloride for sodium. Just like sodium, chloride is highly concentrated outside the cell and rushes inside once the chloride channel is opened. However, because chloride is negatively charged, increasing intracellular chloride decreases the likelihood of post-synaptic neuronal activation—making GABA inhibitory. The interactions between glutamate and GABA maintain balance in the brain.

At this point, you might be wondering how exactly this relates to ASD etiology. This is the part of the post where I admit that some of what I just told you was wrong. You see, every first-year neuroscience student learns about glutamate and GABA as I just described it, it’s a foundational “ying-and-yang” pillar of neurotransmission. And while it’s true that GABA works like that “most” of the time,  GABA works the exact opposite way during brain development.

During development, GABA is excitatory—as crazy as that might sound! The brain achieves this by implementing two different chloride ion pumps at different stages of development; an importer and an exporter. During fetal development, the chloride importer (NCKK1) is active and establishes a high intracellular chloride concentration. Once GABA binds and opens its receptor negatively-charged chloride rushes out, causing a net positive effect which makes the neuron more likely to fire—essentially excitatory. This mechanism is critically important during early development, but as fetal development draws to a close an excitatory-inhibitory GABA shift happens. NCKK1 is deactivated and the chloride exporter pump (KCC2) is activated, establishing the typical inhibitory functions of GABA.

This GABA shift is hypothesized to malfunction/be delayed in the context of ASD. This can cause the brains of individuals with ASD to have too many connections, sensory overload, enlarged cerebrums, and other symptoms of ASD. This begs the question, what dysregulates the chloride ion pumps and causes the malfunctional GABA shift in the first place?

Interestingly, these changes are impacted by changes in the maternal environment during pregnancy. Specific factors (especially prenatal infection and stress) can elevate pro-inflammatory cytokines, one of which (IL-1b) may directly impair the excitatory-inhibitory GABA switch! A rat model of ASD demonstrated that the administration of an NKCC1-blocking drug one day before birth restores many brain functions, especially in the hippocampus, compared to controls. This shows that birth is a critical period for the GABA shift and by proxy ASD development. This same drug decreases ASD symptom severity in humans with few side effects and is a promising avenue of treatment.

https://www.nature.com/articles/s41398-020-01027-6/figures/1

The take-home message is that maternal inflammation can cause prenatal neuroinflammation and impair the inhibitory-excitatory GABA shift, which can cause excitatory-inhibitory imbalances throughout postnatal development, increasing the risk of ASD. Understanding how these ion pumps initially go “out of whack” can help researchers design better drugs that more effectively repair the GABA switch with the fewest side effects!

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The Tangled Web of Autism Spectrum Disorder

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Do you remember the first time you saw a spider’s web? If you are like me, you were a young kid looking at it in a state of wonder. How can a spider create such a thing? Each thread looks perfectly placed and is clearly there for a reason. The threads come together to paint a picture of one of the most awe-inspiring parts of nature. I like to think of our brains in a similar way. Millions upon millions of connections come together, painting an intricate web between our ears, that ultimately makes up who we are.

The Web of ASD

Now I want you to think about taking that web and adding more and more threads. Now the perfect spider web is becoming muddled, with threads on top of each other where there shouldn’t be. Where there should be threads, there are too many, and now this perfect picture is becoming more and more confusing the more you look at it. This web does not look as functional, and it leads one to wonder what went wrong.

We can think of the brain, in almost an identical way to the muddled web as it relates to ASD. The causes of ASD are complex, to say the least, and involve a myriad of genetic and environmental risk factors. The effects, particularly on neural circuitry, are much better understood. Revisiting the spider web analogy, there are simply too many neuronal connections in ASD, as there would be in a crowded web. In a normal brain, around early childhood, neurons are pruned and refined to make connections more efficient. So in a more complex web, if a spider wants to travel from one side of the web to another, they are met with many more crossroads than would normally be anticipated. The spider ultimately takes longer to cross the web. Similarly in the brain, if a message needs to be sent across a greater distance the extra neuronal connections will mean that message is delivered slower and less efficient.

artract created by B. Swanson

Further complicating the brain in ASD, neurons can also simply be in the wrong place. Indeed, neural migration is also affected during ASD and during development. Now you can imagine a web with threads where they should not be, it does not look right, and maybe not even function right. With neurons in the wrong place, the issues of neural communication are further complicated.

Bringing it all Together

            With the brain seeming so out of whack, it’s hard to imagine a scenario where this brain even work. In ASD, the brain is largely functional, however it would not be considered neurotypical. The inefficient wiring leads to some of the big picture symptoms such as:

  • Difficulty with verbal and non-verbal language
  • Gestures
  • Facial expressions
  • Expressions of emotion
  • Lack of understanding of person space

The big picture symptoms are a result of a tangled web of neurons. However, the neurons mostly get the job done, and the messages sent, despite the difficulties. Much like a tangled spider’s web, it may not look and act how it should, but in the imperfection, there is a level of beauty.

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Pandemic Pregnancies and Autism

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Pregnancy during the time of a pandemic can turn a beautiful, life changing experience into a scary, life changing experience. Most women while pregnant experience paranoia and worries already about getting sick, but during a pandemic this fear most likely heightens immensely. It has been noted that infection during pregnancy can negatively effect the fetus, especially if the immunological response to the infection reaches the fetuses blood circulation supply. Some responses, such as certain antibodies, can be helpful to building the fetus’s immune system, but others, like cytokines, can harm the fetus’s development. Some studies have found that if the fetus is exposed during time of infection or if the mom has a fever in response to infection, there is a higher risk of autism diagnoses. So, the question remains, how will Covid-19 affect children whose mothers tested positive while pregnant?

What happens during infection?

Image showing the events leading up to cytokine storm and how cytokine storms can affect the body.

Over the past year, scientists have been trying to become more familiar with the novel Covid-19 pandemic that has struck all around the world. It seems to be a bit of a difficult task, although, due to the variety of symptoms and uniqueness of each  case. It has been shown in case studies of patients with Covid-19 that those who present with existing conditions (hypertension, diabetes, obesity) have a higher risk of death or longer recovery period with longer lasting symptoms. Depending on the severity of symptoms and infection, patients can experience a multitude of aspects caused by the virus. This includes a vulnerable immune system, implications to the neural system, a correlation to the hyperandrogenic phenotype, or cytokine storms. Here we will focus on the cytokine storm aspect of Covid-19. Cytokines are pro-inflammatory molecules that are activated in response to infection. In normal amounts, cytokines can be extremely important in immune responses, but at too high of an amount, they can become dangerous to the health of the patient. An interesting aspect about cytokines is that specific ones, such as IL-6, are able to cross into the placental blood supply for the fetus causing adverse neurodevelopment problems.

Covid-19 and Autism

Diagram showing the similarities between Covid-19 immune responses and aspects that contribute autism.

With all of the immune responses caused by the Covid-19 virus, there are potentially complications that could be seen in the future with children whose mothers had Covid-19 during their pregnancy. A problem that could possibly be seen is a correlation in Covid-19 patients and those with autism. But, since autism spectrum disorder (ASD) is defined behaviorally, a correlation between Covid-19 during pregnancy and autism may not be determined for years when the children begin to develop social behaviors. Although, there are some similarities between Covid-19 and other viruses that have been seen to increase the risk of autism. Studies have shown that infections that have the ability to induce a cytokine storm, for example influenza, that occur during pregnancy correlate to a higher risk for autism. One study even showed that there were higher levels of cytokines in the amniotic fluid of women whose children develop autism. Noting this correlation raises the awareness that children born to mothers who had Covid-19 while pregnant and had increased cytokine levels may develop autism in their future. Scientists have already started case studies with moms who have tested positive while pregnant and their babies to hopefully have an understanding of what effects this virus has on fetuses. Even if the outcomes won’t come for years, the research will be extremely beneficial for moms and children effected.

 

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Be Wary of Gut Inflammation!

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Knock-knock brain, it’s your partner-in-crime, the “second brain of the body”, me, your gut! I have more inflammation for you, ready or not. Research has only seemed to have just started revealing how interconnected our brain and gut are to each other. Things that happen in your gut impact your brain and vice versa, so if I were to tell you that not taking care of your gut increases the risk of the development of a handful of disorders, would I have your attention? If you have kids, what about looking out for their chances for something called autism spectrum disorder, or ASD?

Taking a Closer Look at ASD

What’s the big deal with inflammation, anyways? It seems to be involved in more and more diseases/disorders as science progresses, but one that continues to stand out is ASD. This is due to the broad range of pathophysiology that all circles back to an ASD diagnosis. Although the main cause of ASD still remains largely unclear, there are still many contributions and/or possibilities that are currently being explored, including:

  • Neural connectivity
  • Impaired neural migration
  • Impaired synaptogenesis
  • Excitation-inhibition imbalance
  • Broken mirror theory
  • Impaired immunity and neuroinflammation
  • Epigenetics
  • Single gene mutations

There is good reason to believe that ASD originated from disruptions in more than one of these listed above and that one may very well cause another (or more) to become discombobulated. Instead of going through every point listed above, we will analyze just one of the ideas down below: inflammation, specifically originating from the GI.

GI + Inflammation = ASD?

Although there remains to be no scientific proof of gastrointestinal (GI) inflammation being the solo-contributor or major player of ASD development, there seems to be good reason for a relationship between the gut and brain to exist. Chronic or increased amounts of exposure to cytokines in the brain seem to lead to chronic inflammation and ultimately neuron damage and death. The popular term “leaky gut” may play a role in how inflammation even develops within the brain. The gut-blood barrier is very important inside of the body, which prevents things such as undigested food, toxins, and pathogens from crossing over from the GI tract into blood vessels that can then be carried anywhere within the body via the circulatory system.

Scary, right?!

This will trigger an immune response, and when these invaders reach specific places inside the both, like the brain, will cause an “alarm system” to go off and force cells inside the brain to start attacking the invaders. Changes in some of these protector cells in the brain can ultimately result in neuronal dysfunction, some of the same associations with the mechanisms of ASD.

Fig. 1

There is also an incredible overlap with kids who already have ASD that also suffer from GI issues. This in turn has also been reported to make their ASD symptoms worse. A study examined different groups of children, with one group having ASD and GI issues, and found that this group, compared to the rest, not only had increased levels of cytokines, but also different gut bacteria and increased levels zonulin. All groups with ASD individuals experienced decreased levels of a protein that regulates both neurodevelopment and the immune system.

An Optimistic Closing

As the science field continues to make strides towards opening new doors to answer questions about disorders such as ASD, there is bound to be something relating back to the GI tract. These discoveries will have the ability for early diagnosis/prevention as well as effective treatment options for patients and their family. So, until there is enough evidence, be mindful of your body by keeping your gut happy and healthy!

Health

ASD an Overview

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Autism spectrum disorder (ASD) is an umbrella term for a developmental disability that can cause significant social, communication, and behavioral challenges. These individuals typically aren’t distinguishable by appearance but rather exhibit different methods of learning, interaction, and behavior. ASD is described as a spectrum since individuals can exhibit a diverse range of behaviors that vary in severity. High functioning autistic individuals may not be distinguishable from others, they can pursue education, earn a salary, and live independently while low functioning individuals may be nonverbal and require assistance.

ASD is a complex condition with many underlying conditions that influence and contribute to the risk of development. Challenges in studying ASD arise from the complex pathophysiology of the condition which involves neural connectivity, neural migration, excitatory and inhibitory imbalances, increased synapses, lack of mirroring in neurons, neuroimmunity disturbances, epigenetics, and dysfunctional genes, all of which have complex signaling and cross-communication of their own. To keep this article brief, we will only examine a couple of these to observe how they may impact the development of ASD.

Let’s begin by exploring imbalances in Glutamate (primary excitatory neurotransmitter) and GABA (primary inhibitory neurotransmitter). The Excitatory/Inhibitory balance between glutamate and GABA is critical for the proper functioning of neuronal networks and brain functions. It has been found that there are disturbances in glutamatergic and GABA-ergic receptors within ASD patients leading to an Excitatory/Inhibitory imbalance. This results in excessive glutamatergic excitation which may lead to excitotoxicity and cell death, as well as activation of glial cells that stimulate neurotransmission. To summarize, an imbalance in these important chemicals within the brain can lead to overstimulation of the brain and cause damage to neurons which ultimately results in reduced or altered brain function.

Another pathology relates to synaptic pruning. In neurotypical brains, the initial overabundance of dendritic spine formation is selectively pruned to support brain maturation, and this is regulated through a complex process abbreviated as mTOR regulated autophagy. In autism, there is a reduction in developmental dendritic spine pruning resulting in an impairment in mTOR regulated autophagy. Put simply, as we develop from infancy, our neurons make connections with one another some of which (in a healthy brain) are removed to reduce overstimulation and strengthen/reinforce the important pathways. In autistic individuals, this removal of unnecessary neural connections is not performed leading to an overabundance of connections and decreased efficiency in brain processing and communication.

Mirror neurons have also been found to contribute to the development of ASD. In a healthy brain, the mirror neuron system works to help with learning observed actions and emotions, but in autistic brains, fMRI have shown cortical thinning of regions belonging to the mirror neuron system. This means ASD symptom severity can be correlated to the limited development of the mirror mechanism which may appear in behavioral differences between autistic individuals and others.

Though there are several other contributions we could examine, the final component we will explore is genetic mutations which negatively impact synaptic transmission and synaptic growth. Dysregulation in gene networks forming both the synaptic transmission supporting system and the synaptic growth rate are implicated in the development of ASD, but no specific single gene modulation is sufficient to cause ASD symptom formation. This means more research is needed to elucidate the specific gene-environment & gene-gene interactions giving rise to ASD symptoms. This describes that genes play a significant role in the regulation of neural communication and that issues with this are found in patients with ASD. It’s also understood that it isn’t the dysfunction of a single gene that leads to the development of ASD but rather likely the contributions and combinations of multiple genes and uncovering these genes has yet to be done.

This was a brief overview exploring the very basics of a couple factors out of many that contribute to the complexities of understanding ASD. There remains much research to be done on the subject and a cure has yet to be discovered. Understanding the complex pathophysiology of this condition could provide insight into the dysfunction of countless other conditions and yield future treatment strategies.

Sources

https://pubmed.ncbi.nlm.nih.gov/28499914/

https://www.cdc.gov/ncbddd/autism/facts.html#:~:text=Autism%20spectrum%20disorder%20(ASD)%20is,social%2C%20communication%20and%20behavioral%20challenges.

http://neurochemistry2020.pbworks.com/w/page/141966597/Advances%20in%20understanding%20the%20pathophysiology%20of%20autism%20spectrum%20disorders

Community/Disease

Broken Mirrors: Mirror Neurons and ASD Symptoms

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We learn by watching others. As we grow and develop, we learn how to speak, behave, and even think based on our observations of other humans. Much of this learning is dependent on a part of the brain known as the mirror neuron system. But what happens when the mirror breaks? Read on to find out how this system works and how its dysfunction may contribute to symptoms of ASD.

ASD on the Brain

Autism spectrum disorder (ASD) is diagnosed in roughly 1 in 68 children as of 2017. ASD is characterized by a triad of symptoms: 1. impaired social interaction, 2. language difficulties, and 3. stereotypical (repetitive) behavior.

Many theories have been raised to suggest what causes ASD in the brain. As of yet there is no definitive, accepted, all-encompassing theory. However, most prevalent modern theories boil down to four abnormalities on the neuronal (brain cell) level: synapse construction, impaired protein turnover, impaired regulation of protein expression, and structural modification. Let’s define those terms and take a look at how they’re implicated in ASD.

Synapse Construction

  • Synapses are the spaces between neurons. If one neuron sends a signal to another, the chemicals (known as neurotransmitters) that transmit the signal have to cross over the synapse between them.
  • In ASD, the brain has many more neurons than expected. Normally, the brain prunes (gets rid of) extra neurons that are not being used. This way the neurons aren’t wasting energy and resources that could instead be used to strengthen connections among neurons that often communicate with one another.
    • With the elevated number of neurons in ASD, the connections are not as strong, and there is a lot of extra ‘noise’ from connections that are not necessarily needed.

Impaired Protein Turnover

  • Learning occurs due to a process known as long-term potentiation (LTP) in the brain that semi-permanently strengthens connections among neurons. In order for LTP to occur, expression (creation) of certain proteins needs to occur. Creation of these proteins is dependent on a signaling pathway known as the mTOR pathway.
    • In ASD, there may be an impairment in the mTOR pathway, resulting in interruptions in LTP and learning.
    • mTOR is also important in pruning neurons, so impairment in the pathway could impact synapse construction as well.

Impaired Regulation of Protein Expression

  • As explained above, correct levels of protein expression are essential for all of the brain’s functions. Protein expression is dependent on genes; DNA in genes is ‘read’ and transcribed to make proteins.
  • Epigenetics is the process of genes being modified by environmental factors. If genes are methylated, methyl molecule groups are added to them, and these block the gene from being read. Methylation is important so that genes coding for development stop being read and transcribed, but too much methylation can silence genes that should be being transcribed into proteins. Epigenetics have been proposed as a factor in causing ASD as environmental factors may impact development.
  • Hundreds of gene defects have been found to result in autism, but there is no one ‘autism gene’. Some impacted genes have been found to affect synaptic growth while others impact synaptic transmission (communication among neurons). The problem seems to involve the suppressors of these genes being incorrectly expressed.

Structural Modification

  • Altered synaptic activity due to reasons explained above may cause demands that physically change the synapse’s structure such as altered numbers of ion channel receptors (receptors that react to neurotransmitters to let electrically charged ions into and out of the cell).
  • Reelin is a gene that plays an important role in organizing the brain and making sure neurons are where they need to be during development. Mutations in the reelin gene have been implicated in ASD.

Phew; that was a (maybe not so) brief overview of neuronal differences that have been found in ASD. Causes of these abnormalities have been theorized, as mentioned in some of the bullet points: genetic and environmental causes have been theorized, as has inflammation. We’re going to look into a recent theory of what might be causing some of those above molecular changes and the symptoms of ASD: the mirror neuron system.

Mirror Neurons

So, what are mirror neurons? First of all, they’re normal neurons with specific functions. Many mirror neurons are located in the motor cortex of the brain, which involves motion, and fire when the body does a specific action. Others are in the somatosensory cortex, which involves pain and sensation, and are activated when touching something or experiencing pain. However, what makes mirror neurons special is that they don’t just activate when you move or feel pain; they also activate the exact same way when you observe another person moving or feeling pain. This ‘mirroring’ activation is important in learning and empathy.

The mirror neuron system has a wide variety of functions when working normally. It develops in infants before they have reached 12 months of age and begins to let them understand others’ actions. As the famous Hebbian theory of neuroscience states, “cells that fire together, wire together”. This means that cells that are activated simultaneously form connections. This is also known as associative learning as it results in the brain forming an association between the two objects or concepts (for example, a glass of water and the feeling of thirst). Language development, which is in some ways a form of associative learning, also involved this system.

Mirror neurons have also been implicated in intention understanding; the deductive understanding not just what a person is doing (drinking a glass of water) but why they are doing it (that person must be thirsty). Mirror neurons are often involved in emotions and empathy as they system allows us to understand and relate to fellow humans. Finally, the mirror neuron system is important in what is known as the theory of mind, being able to imagine what another person is thinking or feeling on a more nuanced level than simple intention understanding.

The ‘Broken Mirror’ in ASD

With that brief introduction, we can see that the mirror neuron system is quite important in many higher-order brain functions like language, learning, and empathy and that issues with the system could result in significant developmental problems. The “broken mirror” mirror neuron theory suggests that an issue in this system is the cause of ASD. The theory posits that problems with dendritic morphogenesis (the shape of a neuron’s dendritic spines, an area that forms the receiving end of the synapse) resulting from synapse-related causes mentioned above are a large factor contributing to ASD.

Evidence for this theory is found in the fact that the mirror neuron system doesn’t activate the same way in ASD as it does in the non-ASD brain. As mentioned above, the mirror neuron system typically activates in the exact same way when you complete an action and when you observe another person complete that same action. In individuals with ASD, the mirror neurons activate when they complete the action, but not to the same extent when observing another person do so. It’s not all-or-nothing; the system typically still activates, and some studies have found that there isn’t a significant difference since there is so much variability, but on average there is less activation in the ASD brain.

When we consider all the functions that the mirror neuron system is responsible for, it makes sense that abnormalities could be blamed for ASD symptoms including difficulty with language, self-identification, imitating others, and intention understanding. The theory remains far from conclusive and more research needs to be done to find the role that the mirror neuron system plays in ASD, but for now, it presents a compelling theory for what could be causing ASD symptoms: a broken mirror.

Disease/Health

The Importance of Autism Spectrum Disorder (ASD)-Friendly Healthcare

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What is Autism Spectrum Disorder (ASD)?

Autism Spectrum Disorder (ASD) is a developmental disorder that affects an estimated 18 million people worldwide. This disorder results in disruptions in social, cognitive, and behavioral functioning as individuals with this condition are more likely to have difficulties interacting with peers, communicating with others, and may experience repetitive or obsessive behaviors.

There are numerous molecular mechanisms that contribute to the development of many of the symptoms within ASD, including an excess of neurons and synapses within the brain. This surplus of synapses leads to overstimulation of the senses, resulting in greater sensitivity to light, noise, and tactile stimuli in many individuals with ASD. 

Health Disparities in those with ASD

Individuals with Autism Spectrum Disorder, compared to adults without ASD are twice as likely to develop:

  • Diabetes 
  • High Blood Pressure and Cardiovascular Diseases
  • Gastrointestinal Disorders
  • Psychological Disorders (e.g. Schizophrenia, Depression)
  • Neurodegenerative Disorders (e.g. Parkinson’s Disease)

On average, individuals with ASD have a life expectancy that ranges from 20 to 36 years shorter than those without the disorder. Additionally, the suicide rate of a person with ASD is 9 times greater than the general population. 

Although having ASD indeed increases vulnerability to various health conditions due to physiological consequences of the disorder, many other factors contribute to the greater risk of comorbidity. A prominent factor is the degree to which ASD individuals have access to affordable health care as a result of socioeconomic status. Studies have shown that children with ASD have both greater healthcare costs and needs, yet they maintain poorer access to affordable healthcare than children without the disorder. 

Additionally, both children and adults with ASD may be deterred from pursuing healthcare due to an extreme deficit in accommodations for patients with ASD in both inpatient and outpatient settings. As mentioned above, many of those with ASD experience an overstimulation of the senses as a result of excess neural connections. Since healthcare settings are filled with bright lights, countless noises and beeping sounds, and other intense sensory stimuli, ASD individuals may avoid essential services due to this overwhelming characteristic of the healthcare environment. This aspect demonstrates the need for the development of ASD-friendly healthcare initiatives that make the healthcare experience more individualized and comfortable for each patient with ASD. 

ASD-Friendly Healthcare

Many of the following strategies have already been introduced in various healthcare settings across the nation, including Boston Medical Center in Massachusetts. 

These strategies include: 

  • increased access to and affordability of healthcare services that are geared towards ASD patients 
  • education and training of healthcare personnel to increase awareness of how they can treat their patients with ASD with highest level of respect and compassion
  • individualized care plans, in which the patient with ASD fills out an autism support checklist (ASC) that collects patient preferences regarding preferred communication style, triggers, sensory sensitivities, and other considerations of the patient
  • providing ASD patients with information that will detail exactly what their healthcare appointment will entail in order to decrease anxiety before and during the appointment
  • specific rooms that have reduced fluorescent lighting and fewer noises
  • alternative communication methods (e.g. communication picture cards, whiteboards, tablets, etc.)
  • a “sensory toolbox” that the patient can use to increase level of comfort during the visit. In this toolbox there might be noise-cancelling headphones, sunglasses, fidget toys, communication cards, and other helpful objects.

Autism and Gynecology: A primary example for the need of ASD-friendly healthcare

Reproductive health procedures and examinations can be quite overwhelming and uncomfortable for any patient. This level of discomfort can be amplified in those with ASD, as overstimulation of the senses and a detrimental lack of accommodations accompany these appointments. This unfortunate reality contributes to many women with ASD avoiding these appointments, putting them at a much higher risk for countless genitourinary complications, including cervical cancer that would be detected via pap smears.

This area of medicine therefore demonstrates a large need for numerous strategies and accommodations to make gynecologic appointments more comfortable for patients with ASD.  These strategies include:

  • thoroughly explain the procedure steps, how long the procedure may take, and how this procedure contributes to the maintain of their reproductive health
  • provide charts, pictures, and anatomical models that can further explain the procedure
  • reducing the amount of time the patient is undressed
  • ask/warn the patient before touching them
  • continue to ask them throughout the procedure if they are comfortable/feeling okay
  • come up with a word or sign that signals they need a break from the procedure

Looking Ahead

Individuals with ASD are at much greater risk for developing cardiovascular diseases, gastrointestinal disorders, and other conditions than those without ASD. However, they are often deterred from seeking out services that will reduce the risk of comorbidity due to the overwhelming and uncomfortable environment within healthcare settings. As awareness increases regarding the initiatives pursued by healthcare settings across the nation in the hopes of accommodating ASD patients, more inpatient and outpatient settings will hopefully adopt some of these same strategies.

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Decoding Autism Using Dogs

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Autism affects 1 in 68 people, according to the CDC’s autism monitoring network. Chances are that you probably know someone with Autism, and have seen its effects firsthand.  Autism has been called a uniquely human disorder, as in it may be one of the only disorders that is solely found in humans. For me, this brought up the question: are there animals that have autism? And if not, then why is it just humans that we see the disorder in? 

 

Scientists went looking for any animals that might display some of the behavioral characteristics that are typical of Autism Spectrum Disorder (ASD) individuals. The problem with this is, how do you know if you’ve found autism? Autism can unfortunately still be somewhat difficult to diagnose from a very young age, and so if we as humans have issues diagnosing it within ourselves, it could be even more difficult to actually pin down when observing an animal. 

 

Researchers also specifically looked at several different species such as dogs, cats, and monkeys, which have more similarities with humans than some animals would. Although most of the animals they looked at had inconclusive symptoms, they did discover similarities in a breed of dog called Bull Terriers, which they found to display some of the (dog equivalent) behaviors that can be diagnosed as autism in humans. I say “dog equivalent” because some of the staple behaviors of ASD are very difficult to distinguish in animals that can’t talk, such as imparied social interaction and not being able to communicate properly, which in humans can manifest as an inability to formulate speech or something similar. 

 

These Bull Terriers were found to avoid other people and dogs at a rate that was higher than most other breeds. Another common behavior found in autism is performing repetitive or ritualistic behaviors, and these dogs would also chase their tails for an abnormal amount of time. I know this sounds strange, as in, “so what, the dog is just chasing their tail, they do that”. But if you think about it, if you saw a dog that was chasing its tail for over twenty seconds, (count that out and imagine it if you need to) it stops being cute and playful and starts becoming a little worrisome. These dogs would also have outbursts of anger, another behavior found in autism. This is along with all of these behaviors being found in predominantly male Bull Terriers, which is how also the case with human ASD. 

 

Now, behaviors by themselves don’t signify autism, so researchers needed some sort of biomarker that they could actually measure to see if physiology of these dogs also matched some of the physiological effects found in humans with ASD. Specifically, they looked at Neurotensin (NT) and Corticotropin-releasing hormone (CRH) levels in Bull Terriers, as they have been found to be elevated in humans with autism. What they found was that the results (levels) in dogs were similar to that of humans, which is an amazing piece of evidence that links up not just the behavioral aspect of autism with animals, but also potentially the physiological side of things too. 

 

But why does it matter that some Bull Terriers might have the dog-equivalent of autism?

To be able to more effectively learn about, treat, and live with autism (or almost any disorder for that matter), scientists use animal models to be able to figure out things about how these disorders operate. Using animals as test subjects (for the advancement of science), we can further understand how autism might arise genetically, or how to treat its symptoms once it does come about. One of the main goals with treating autism is to try give the individual as normal of a life as they can live, and so using this breed of terrier to try figure that out could improve the lives of countless people with ASD (including the dogs too!). Knowledge is power in the world of science and medicine, so being able to aid with a disorder that has plagued so many would be a worthy achievement.

 

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