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Pooja Kumar

CAPSTONE 6TH PERIOD

Autism Spectrum
Disorder
Causes, Treatments, and the Future

OVERVIEW
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects an
individuals social skills, cognition, and behavior. ASD refers to the spectrum of disorders that
encompass autistic disorder, Aspergers syndrome, and pervasive developmental disorders- not
otherwise specified (PDD-NOS). As of 2016, approximately one in every 68 children is
diagnosed with ASD (Data & Statistics). Over the past decade, this number has been
increasing exponentially. This rise in the number of cases of ASD can partially be attributed to
changes in genetic and environmental conditions. Anomalies in the genetic sequences of the
body or transformations in the environment can disrupt normal functions of the body, causing
autism.
From changes in the synapse structure, to enzyme malfunctions, to small genetic
anomalies, autism spectrum disorder (ASD) is known for having a wide-range of potential
causes. It is often referred to as a heterogeneous disorder, meaning that the symptoms and
intensity of the disorder vary from person to person. As of now, autism does not have a defined
etiology which makes it difficult to determine holistic treatments for it. Additionally, in certain
cases, individuals may have several gene/chromosomal abnormalities which may make it
ineffective to treat the condition with only one standard therapy. As a result, current therapies for
autism, such as speech and behavioral therapy, focus on helping autistic people develop specific
categories of skills rather than treating the issue as a whole. These therapies strive to improve
skills in individuals on the spectrum and may mitigate the intensity of the symptoms, but do not
remove them altogether. Pharmaceutical companies and other researchers are currently focusing

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on developing new drugs and biological treatments like induced pluripotent stem cells in order to
treat autism as a whole and potentially eliminate its symptoms.
It is crucial for doctors and researchers to gain a thorough understanding of the etiology
of autism first in order to determine potential treatments and cures for it. After that hurdle has
been crossed, the next step will be to identify symptoms of autism at a young age and make the
diagnosis earlier on so that the therapies work more effectively. This can be aided by the
development of newly discovered technologies which have been pivotal to diagnosing autism
earlier.

ETIOLOGY: GENETICS & THE ENVIRONMENT


One known cause of ASD is changes in the basic genetic structure of the human genome.
Mutations in the chromosomes and other genetic structures can cause uncontrollable changes in
different body functions which can lead to autism. One specific genetic mutation identified by
Dr. Christian Schaaf is de novo copy number variants. Every person has two sets of twenty-three
chromosomes, one set that they inherit from their mother and the other that they inherit from
their father. However, a study conducted by Dr. Schaaf suggests that autistic people tend to have
between 0-1 or 3-4 sets of 23 chromosomes (Schaaf and Zoghbi). This anomaly results in slowed
development of the brain and intellectual disabilities that are typically seen in autistic people. In
addition, using the study, Dr. Schaaf and Dr. Zoghbi establish[ed] de novo copy-number
variants (CNVs) as the cause of 5%-8% of cases of simplex autism. Since ASD encompasses a
spectrum of disorders that have various causes and symptoms, finding a cause that accounts for
5%-8% of the cases of autism can be very useful when determining the etiology of ASD. Another
common genetic mutation that has been known to cause ASD is single gene mutations which

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refer to anomalies in the genetic structure caused by DNA changes in one specific gene.
Typically, this means that there is either a duplication or deletion of the gene, meaning there is an
extra copy of the gene or none at all. Through the Levy and Sanders studies, Dr. Schaaf was able
to identify new loci, the position of a gene or mutation on a chromosome, like CDH13 and
16p13.2 which refers to segment 13.2 in the upper arm (p) of chromosome sixteen. Like copy
number variants, these single gene mutations alter the genetic structure of DNA and manifest as
symptoms of autism like learning disabilities and a lack of motor skills. Researchers have also
identified synaptopathies as a major cause of ASD. Synapses are parts of neurons that allow
information to travel throughout the nervous system (Schulz et al.). They also aid in adjusting
behavior to environmental stimuli and controlling body functions like memories and emotions
(Schulz et al.). As a result of this, it is crucial that synaptic communication is in its best
condition because even a slight mistake of its function can result in brain disorders like ASD.
Understanding how synapses work and how synaptopathies affect the brain will allow
researchers to tailor treatments to reverse the aberrations in the synapses, potentially curing ASD.
The second known cause for ASD is toxic environmental conditions. Researchers have
suggested that extensive exposure to pyrethroid pesticides, heavy metals, and mercury can lead
to autism. Pyrethroids are a type of insecticide that are used by pest management companies to
prevent plants from being consumed by insects. Studies have suggested that newer pyrethroids
have been known to be more toxic to insects and last longer in the environment. This can be
detrimental to a persons health because increased exposure to toxic chemicals can directly harm
the brain and impair its functions. Although pyrethroids are excreted within 24 hours, thus
limiting the impact of body accumulation, they are characterized by pronounced lipophilicity
which makes them able to easily cross the blood-brain barrier and exert their toxic effect directly

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on the central nervous system (Domingues et al.). Damage to the central nervous system can
lead to impaired mental ability, lack of coordination, and other symptoms that are typically found
in ASD patients. Data has also suggested that the presence of heavy metals in the environment
contribute to ASD. Metals like zinc, copper, and nickel enter the bloodstream by various means
and disrupt the brains function, causing autism. Researchers speculate that high levels of certain
metals in children with ASD could be because of a diet rich in fish, environmental exposure to
gasoline or use of aluminum pans by mothers for cooking (Domingues et al.). The third main
environmental factor contributing to the etiology of ASD is mercury. The review conducted by
Kern et al. found 91 studies that examine the potential relationship between mercury and ASD
from 1999 to February 2016. Of these studies, the vast majority (74%) suggest that mercury is a
risk factor for ASD, revealing both direct and indirect effects. The preponderance of the evidence
indicates that mercury exposure is causal and/or contributory in ASD. Increased levels of
mercury in the body can harm the brain and lead to symptoms that are akin to those of autism.
Although genetic conditions are not under humans control, changes in the environment can be
closely monitored and checked. It is crucial to determine which environmental factors contribute
to ASD in order to eliminate them and reduce the number of cases of autism.
Over the past decade, the number of people diagnosed with ASD has increased ten-fold.
In 2000, 1 in every 150 children was diagnosed with autism. That number has grown to 1 in
every 68 children as of June 2016 (Data & Statistics). The rise in the prevalence of autism has
led several researchers to question the reasoning behind it and determine what can be done to
slow down the rapid rate at which it is growing. Some researchers believe that this is due to a
redefinition of autism spectrum disorder in the DSM-V manual. The Diagnostic and Statistical
Manual of Mental Disorders (DSM) lists all the neurodevelopmental disorders that are known as

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of now and defines criteria for each condition. In the past the definition of autism in the DSM
has been very specific, but researchers argue that recent changes to the manual and a broader
definition of autism has led to more people falling under the category of ASD (Lathe). On the
other hand, several researchers also argue that increased pollution and use of toxic pesticides are
the main cause for the rise in prevalence of autism.
Autism spectrum disorder is a neurodevelopmental disease that impairs the regular
function of the brain. This can be caused by changes in the genetic sequence or toxic
environmental conditions. Identifying the exact etiology of ASD is extremely important in order
to determine potential cures and treatments for it.

CURRENT TREATMENTS & THERAPIES


The main three types of therapies offered for patients with autism include speech therapy,
occupational therapy, and behavioral therapy. Speech-language therapy is designed to
coordinate the mechanics of speech with the meaning and social use of language (Autism
Speaks). Often, many autistic people have speech delays or social issues that make them hesitant
and scared to speak in a social setting. Additionally, many of them often have difficulties
understanding verbal or nonverbal cues (Lathe). In situations such as these, speech therapists can
help patients master spoken language and/or learn nonverbal communication skills such as signs
or gestures (Autism Speaks). Effective communication is a skill that is necessary in all aspects
of life, which is why it is crucial for people with autism to undergo speech therapy if they are
struggling to express their thoughts and ideas. The second most common type of therapy is
occupational therapy. This addresses a combination of cognitive, physical and motor skills...
and [aims to help people] gain independence and participate more fully in life (Autism Speaks).

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In other words, occupational therapists help autistic people to develop self-care skills such as
independent dressing, use of the toilet, feeding, and grooming. Apart from that, occupational
therapists also focus on refining motor and visual skills such as eye-tracking and hand-eye
coordination. The third main type of therapy is behavioral therapy. This type of treatment focuses
on changing potential destructive behaviors such as uncontrolled anger and social anxiety
(Lathe). Essentially, behavioral therapy permits therapists to help patients replace bad habits and
feelings with good ones. All these therapies focus on treating different categories of autism
symptoms by helping autistic people develop social, cognitive, and behavioral skills.
Recently, researchers have spent extensive resources and time trying to develop new
therapies and treatments for individuals with autism. One of the major breakthroughs they have
discovered is the positive effects of environmental enrichment therapy on people diagnosed with
autism. This type of therapy changes the environmental stimuli that individuals with autism are
exposed to in order to mitigate the intensity of autisms symptoms. For example, parents may be
asked to provide a changing set of sensory exercises for their children such as being exposed to
different fragrances every day or listening to different types of music before sleeping.
Researchers believe these changes lead to benefits because a study testing the effects of
environmental enrichment therapy showed significant overall gains for a wide range of
symptoms in children, including learning motor skills sensory processing,
communication, and social skills (Aronoff). These positive results have led to further research
on this type of therapy because of its low costs and high efficacy. Although none of these
therapies can cure autism, they help autistic people cope with everyday life and develop skills
that are useful for daily tasks.

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Early intervention is crucial for all the current therapies and treatments to work
effectively. Over the past decade, researchers have discovered new technological devices that can
be used to diagnose autism earlier than conventional ones can. One common device is whole
exome sequencing (WES) which is a technology that compares the DNA sequence of a person
with autism to a sequence of a neurotypical person (Brian). Through this, doctors are able to
identify locations where there are differences in the sequences of individuals on the spectrum.
WES is very common especially since many geneticists claim it is one of the best and most
thorough genetic tests available (FAQs). Typically, if a patient is seen to have symptoms of any
genetic condition, geneticists recommend that they request a WES test to confirm if they have a
specific disorder (FAQs). This technology can be very useful in diagnosing autism early because
a simple genetic test can identify common loci (location of the mutation) for autism, making it
easier to diagnose the condition. Chromosomal microarray analysis (CMA), another diagnostic
technology, works in a similar manner. It uses a persons blood and analyzes the DNA sequence
in order to determine locations of mutations (Brian). Both of tests can be conducted as young as
the age of 1, and is known to be very accurate and reliable. Although the WES and CMA tests
cannot find a specific gene for every single genetic disorder, they are able to identify major
genetic anomalies that predispose an individual to ASD and other genetic conditions (FAQs).
These types of technology can be useful in identifying and diagnosing autism at a young age,
which can be extremely helpful if the individual wants to seek out therapy and other types of
treatments.
Current therapies are designed to treat different categories of symptoms like cognition or
behavior. Early intervention and detection of autism can be pivotal for individuals on the

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spectrum to develop a positive and healthy lifestyle. With the rate research is progressing, there
is no doubt we will soon be able to predict, define, and treat autism spectrum disorder.

THE FUTURE: NEW DRUGS & TREATMENTS


Research on new and unconventional treatments for autism has completely revolutionized
the field of medicine. Conventional pharmacological agents [for autism] include
antipsychotics, antidepressants, mood stabilizers, and medications targeting inattention and
hyperactivity (Sung et al.). However, new research has placed an emphasis on developing
novel treatments [such as] melatonin, omega-3 fatty acids, and oxytocin (Sung et al.).
Melatonin is a neurohormone secreted by the pineal gland [that] causes drowsiness (Sung et
al.). It is currently being used to treat sleep disorders in children diagnosed with autism and so
far, researchers claim it has been useful in improving the overall quality of sleep for children. In
fact, in one trial with 107 children, 85% of parents reported partial or complete improvement in
sleep (Sung et al.). Although larger trials are needed to confirm the positive effects of using
melatonin to treat sleep disorders in autistic children, it has proven to be useful in improving
sleep latency and the overall quality and duration of sleep (Sung et al.). Omega-3 fatty acid
supplements is another novel treatment that has had success in ameliorating the symptoms of
autistic individuals. For this particular treatment, there are different types of fatty acid
medications that can be administered for ASD. The three main fatty acids found in the human
body include ALA (alpha-linolenic acid), DHA (docosahexaenoic acid), and EPA
(eicosapentaenoic acid). These substances are often referred to as essential fatty acids, and neural
tissues are known to have high concentrations of them (Trafton). Research has suggested that

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these fatty acids are essential to the growth and functional development of the brain, but not
enough trials have been conducted yet to determine conclusive results (Trafton). The third major
factor being researched is oxytocin which is a hormone released by the pituitary gland. Current
research suggests that neuropeptide oxytocin may play a role in the etiology of autism (Green
et al.). Studies have indicated that autistic individuals with oxytocin infusions show reduced
repetitive behaviors and improved affective speech comprehension from pre- to post-infusion
(Sung et al.). Oxytocin is known for playing a big role in social memory and recognition, stress
response, and the regulation of feeding and grooming which is why it is crucial for this
treatment to be researched even more thoroughly (Trafton). As of now, these drug therapies are
not very common or widespread and still are in their testing stages (Trafton). As a result, they are
not completely reliable yet, but as more research is conducted on them, there is no doubt that
they will be a more effective and efficient alternative to conventional drugs and therapies.
Researchers have also been focusing on developing new biological techniques to help
mitigate or potentially remove the symptoms associated with autism. One example of this
includes induced pluripotent stem cell technology. Gene therapy refers to an experimental
technique that uses genes to treat or prevent disease (U.S National Library of Medicine). Using
this technology, doctors may be able to treat a disorder by inserting or removing a gene from a
patients cell instead of using drugs or surgery. The three main ways to do that are by replacing
the mutated gene with a healthy copy, knocking out the mutated gene, or introducing a new gene
in the body to help fight the disease (Lathe). However, in order to do this in a safe and effective
manner, researchers have to identify specific mutations or causes for autism which is why it is
important for them to define the etiology of autism before they begin to treat it. Using gene
therapy to treat autism is a lot more difficult than it is for other disorders because there are

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several mutation locations and genes involved with ASD. As of now, most gene therapies focus
on removing one single mutated gene or adding in one new gene which is why it may be difficult
to treat autism with this method since it has so many genes and mutations associated with it
(Lathe). Currently, gene therapy is primarily being tested in animal models like mice and
primates, but it is slowly expanding to human models too (U.S National Library of Medicine).
This technology is also very expensive which doesnt make it a viable solution now, but as
technology develops and research progresses, gene therapy will become a cheap and effective
way to treat autism.
New research has focused on developing biological technology like induced pluripotent
stem cell technology. Through this process, researchers are able to reprogram specialized cells in
the body into stem cells. These stem cells are now pluripotent which means that they can be used
to create any other type of cell in the body like muscle or brain cells. This is particularly useful
for individuals diagnosed with autism because researchers can inject neural pluripotent stem cells
that dont have any mutation by reprogramming skin cells into brain cells (Mokhtari et al.). One
of the major benefits of iPSCs (induced pluripotent stem cells) is that they are made from a
persons skin which means the specialized cells that they grow will exactly match the genetic
makeup of the patient, thereby preventing rejection by the patients immune system (Mokhtari).
In individuals with autism, these iPSCs can be developed in the laboratory and replicated so that
there is a good supply of patient-specific and healthy specialized cells available for
transplantation (IPS Cells). This type of technology is definitely very costly and has not yet
been proven to be 100% safe which is why current research is focused on testing the safety of
these stem cells and reducing the costs associated with it (Lathe).

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In order for these treatments and techniques to work effectively, however, researchers
need to clearly define an etiology for autism. Without determining specific genetic mutations or
environmental stressors, it will be very difficult to develop new drugs and biological treatments
to reverse the symptoms of ASD. As time continues to pass, it is evident that new technologies
and treatments for ASD will be created and tested, potentially curing autism spectrum disorder.

CONCLUSION
With 1 in every 68 people in the U.S diagnosed with autism, it is becoming increasingly
important to determine the specific causes for it. Without knowing that, it becomes very difficult
to identify effective treatments. As our world progresses and new technology develops, there are
better and faster ways to diagnose and prevent symptoms of autism.
There is no doubt that our understanding of autism will only continue to grow over the
next few decades. The future of ASD lies in the hands of our society. It is up to us to conduct
more extensive research if we want to change the lives of thousands of people in the U.S and
across the world.

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