Autism
Relationship to Vaccination
The condition of autism and its symptoms had been described centuries ago before the official term of autism was coined. It was first used in medical literature during the 1940s when doctors such as Hans Asberger and Leo Kanner dealt with children who displayed autistic symptoms. However, it wasn't until 1981 that autism was recognized as a separate diagnosis. At this time, many believed autism to be a rare disorder; studies showed that 1 in 2000 people were diagnosed. But in past decades, the prevalence has increased dramatically to 1 in 88 people.
Currently, there is no known cure for autism. And as there is no known cure for autism, there is no one exact cause for the development of autism. Autism is an ongoing field of medical research that is continually investigating potential causes that may redefine the spectrum. Thus, it is important for everyone to understand what has been established as fact and to clear up the misconceptions associated with this developmental disorder.
In this module we will explore some of the possible causes and risk factors of autism, popular misconceptions people hold, and reputable research disproving the association between the MMR vaccine and autism.
After completing this module, students should be able to:
Autism Spectrum Disorder (ASD) is a broad category for a span of neurological disorders that ranges in severity. ASD is characterized by varying degrees of social interaction, difficulty with communication verbally and non-verbally, attention and motor coordination and repetitive behaviors. There are varying degrees of the severity of symptoms that a person diagnosed with ASD may experience. Further, the severity of symptoms defines where a person diagnosed with ASD falls on the spectrum.
There are three main categories on the spectrum, which may be used to categorize an individual with ASD. Autistic disorder, (also "classic" autism) is the most severe on the spectrum. Individuals with autism usually have delayed speech, communication and social challenges, and unusual behaviors and instincts. Many individuals with autistic disorder display signs of intellectual disability. Asperger's syndrome is the least severe on the spectrum. People with Asperger's tend to have difficulty with social interactions, but usually do not have significant difficulties with language or cognitive ability. Individuals with Asperger's may have a wide range of symptoms including: limited social interactions, challenges with nonverbal communication, lack of eye contact and awkward movements or mannerisms.
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There are more symptom's associated with Asperger's, however, individuals tend to be affected by only a few of these symptoms and they are not all present at one time. The last large category on the spectrum is Pervasive Developmental Disorder-Otherwise not Specified (PPD-NOS). Individuals who have PPD-NOS (also called "atypical" autism) might have some symptoms, but not all symptoms, and don't meet the criteria for ASD or another developmental disorder. However, it is important to remember that each individual with autism is unique and can display different sets of symptoms at varying degrees of severity.
Answer the following questions to see how much you know about autism myths and facts.
Until recently, it was believed that autism was a rare disease and affected only 1 in 10,000 individuals. However, researchers now estimate that 1 in 88 individuals are affected by autism. This disorder affects all races equally, but does affect males more frequently than females. In fact, research states that males are 3.5 to 5 times more likely to suffer from autism. Further, the prevalence of autism has been increasing since the 1970s. However, it is not clear if this dramatic growth is due to a true increase in the number of individuals with autism or related to better diagnosis and more advanced diagnostic criteria.
Patient Voices: Autism is an interactive webpage from the New York Times featuring six individuals of varying ages who have autism or are affected by autism. It offers insight on autism from different points of views.
Symptoms can cover an assortment of disabilities and can vary in severity. Intelligence can range from intellectual disability to gifted while social interaction can range from not being interested in others to having a variety to friendships. Up to 40% of individuals with ASD have above average intelligence while 25% are nonverbal. Nonverbal individuals communicate by other means such as gestures and eye contact. Repetitive or unusual behaviors (i.e., hand flapping or jumping up or down) can range from intense to mild. Below is list of the most symptoms that individuals with ASD might possess.
The diagram below summarizes the symptoms that are most common with certain disorders on the spectrum.
The activity below highlights some of the symptoms related to autism. For a more complete list of symptoms visit the CDC's Autism Spectrum Disorders webpage.
This video features Temple Grandin, a professor of animal science at Colorado State University, who is on the high functioning end of the autism spectrum. In the beginning of the video, she discusses the range of disorders on the spectrum and how there is no "one autistic brain." Later in the video she discusses different therapies that might be helpful to children with autism.
There is no medical test for autism but it can be diagnosed by physicians and psychologists through administered behavioral evaluations. The number of diagnoses of ASD is on the rise, however, it is unclear if the actual number of cases is on the rise or because there are better resources to diagnose and treat individuals with autism. There are several warning signs, or early indicators, that a child might have autism and there are also indicators that appear later in life.
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Although there is no one cause of autism, there are risk factors that have been associated with autism. Autism affects both boys and girls, with boys being four times more likely to have autism than girls. Family history of autism can also contribute to the risk of autism. There is an increased risk for having a child with autism, if the family already has a child with autism. Another risk factor of autism is the presence of other disorders such as fragile X syndrome, tuberous sclerosis, epilepsy or Tourette's syndrome. It has also been suggested that older parental age might be a risk factor for ASD, however, more research is necessary to establish this link.
There is no treatment for the core signs of autism but there many types of interventions that can help symptoms of autism. One of the most important aspects is to begin the treatment early. Early intervention is suggested for children between birth to 3 years of age. As many families may not have an autism diagnosis by this age, these treatment programs are available to any child who is exhibiting signs of delayed development. This type of treatment can help children learn important skills like walking, talking and interacting with others. Another intervention that children with autism benefit from is communication therapy. This teaches verbal skills, social skills and provides parents with techniques of how to address behavioral problems.
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Medication can also be used to treat the symptoms, although it does not help the core signs of autism. Medication is usually prescribed to treat anxiety, behavioral problems, inability to focus, depression or seizures. Recently the Food and Drug Administration has approved the use of aripiprazole an antipsychotic, to treat irritability associated with autism. Some studies have shown that children with autism, even those displaying severe symptoms, can show an improvement as they age into adulthood. However, there is no understood mechanism for this change and this is still a developing area of research. As each case of autism is unique, the best combination of interventions and medications will be different for each individual diagnosed with the disorder.
The theory of causation of Autism Spectrum Disorder is currently incomplete. It has been presumed for a long time that there is a clear and common cause at genetic, cognitive, and neural levels for autism. However, more recent research indicated that autism is a complex disorder with different causes (multiple genes, environment, and epigenetic factors) that can often co-occur.
The image below shows the complexity and multifactorial causes of autism spectrum disorder.
Several different genes are thought to be responsible for causing autism. Genetics could determine child susceptibility, brain development, communication between brain cells, and even severity of symptoms.
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Recent research in mice shows a mutation in the gene that encodes a protein, SynGAP1, severely disrupts how the developing brain circuits organize themselves during first years of life. Gene mutations thought to cause ASD generally affect synapses. SynGAP1 regulates the development of synapses and a mutation can cause abnormal maturation leading to cognitive disruptions. Specifically, it is thought that this mutation causes accelerated development, which leads to higher excitability (nerve cells are "fired" more often/ more easily than normal). This mutation is directly involved in raising the risk of autism. Mutations in this gene specifically are thought to affect one million peoples' disabilities. It is also believed that eventually a cure can be found to repair the mutation during the crucial developmental period.
Mutations in three genes, AKT3, PIK3R2 and PIK3CA, were also found to be associated with various disorders from cancer, epilepsy, skin growths, and autism. AKT3, PIK3R2, and PIK3CA are genes that are present in all humans. PIK3R2 is a cancer-related gene and is known to make cancer more aggressive. These genes were found to be associated with markedly enlarged brain size, or megalencephaly, ranging from anywhere between 7 to 10 percent larger than normal at age 2. Megalencephaly is thought to affect an increase in proliferation of neurons during development. There is particularly an increase in the volume of the cerebral cortex. This discovery is important because it can lead to new treatment possibilities for developmental disorders. Also, it may also become possible to use head or brain circumference MRI as an early detection tool for ASD, which is critical in early intervention.
Research has shown that identical twins of individuals with autism only had 60-90% chance of also having autism, leading to the conclusion that other factors are involved. The image below shows a pyramid of some known environmental factors associated with autism arranged according to number and agreement of studies done. Possible factors include viral infections, complications during pregnancy, air pollutants, and heavy metals. Exposure to traffic-related air pollution, nitrogen dioxide, and particulate matter (PM) during pregnancy and during a child's first year of life may be linked to a higher risk of autism. \\Can make the diagram below interactive or use another one. Be able to explain some environmental theories as opposed to just listing them. Either way this paragraph above needs to be hashed out a little more\\
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The following shows some of the major areas of current scientific research in the field of autism. It can be seen that genetic studies were the most common, although the majority of studies did find strong associations with autism.
A recent review article (2012) searched all medical literature for biochemical abnormalities in ASD:
There are various other theories for a possible cause of autism that are neither genetic or environmental. These range from inflammation in the immune system, mitochondrial dysfunction and links to other mental health disorders.
Using a mouse model, it is currently being researched whether changes in the immune system (connected to the mothers during pregnancy) could be associated with ASD. This could be caused by an immune system in "overdrive," where regulatory T cells are decreased, leading to inflammation conditions.
Genomic research is beginning to discover that people with autism spectrum disorders probably share genetic traits with individuals with ADHD, bipolar disorder, schizophrenia, or clinical depression.
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There are multiple theories, such as mutations in genes and environmental exposure to air pollutants and heavy metals, which have been heavily backed up with much scientific evidence to illustrate as possible causes of autism. However, quite a handful of people believed that there was a causal relationship between vaccines and the development of autism. But why did a part of the population fall into this belief? There was no real scientific evidence to prove this connection. In fact, vaccines were hailed as a breakthrough health practice back in the late 1790's when Edward Jenner discovered how to vaccinate against smallpox by inoculating his son with a cowpox sore and found that his son remained healthy, immune to the disease. This was similar to variolation the Chinese had practiced back in 1000 A.D. except with no actual contraction of the disease.
An anti-vaccination movement emerged in England in the early 1800s after news of Jenner's discovery spread, drawing public criticism due to religious and scientific reasons. Some found that it was "unchristian" to vaccinate because of the vaccine's animalistic origins, while others were simply not comfortable with the practice of medicine. Furthermore, these people held the popular belief that smallpox was spread not by infection but by filth. Similar views were held during that period of time in the United States as well. But since vaccines are one of many methods to protect against deadly diseases like smallpox and measles, there have been campaigns promoting awareness and the safety of vaccines.
More anti-vaccination debates continued throughout the 20th century. In the 1970s, the DTP (Diphtheria, Tetanus, and Pertussis) controversy exploded internationally, concerning patients who developed neurological conditions after receiving the vaccine. In response, lawmakers passed the National Childhood Vaccine Injury Act (NCVIA) to relieve the public distress by promising compensation to victims of the DTP vaccine. Other controversies related to vaccines and the prevalence of autism have also developed--though on a smaller scale--such as the aluminum vaccine.
In 1993, the first study that suggested some type of association between vaccines and inflammatory bowel disease (IBD) was conducted by Dr. Andrew Wakefield, a British gastrointestinal surgeon. He went on to publish more related papers, including an article regarding the measles vaccine as a risk factor for the incidence of IBD. Interestingly, Wakefield briefly mentions that not only is there an association between the measles vaccine and bowel disease, but also an observation that patients with IBD "are more likely to have had certain childhood diseases, including, but not limited to, mumps, rubella, and most importantly, autism.
One recent controversy goes back to the early 2000s arguing that thimerosal, found in vaccinations, was the direct cause of incidence in autism among child patients. Thimerosal is an ethyl mercury-based compound used in vaccines to preserve shelf lives and prevent bacterial and fungal contamination. It has been proven to be safe so far in that very low concentrations are found in vaccines. Also, when the vaccines are administered, thimerosal breaks down into ethylmercury and thiosalicylate, both compounds which are eliminated from the body and brain easily.
Named the "Thimerosal Controversy", it was claimed that this preservative used in vaccinations was the reason for the increasing number of cases in autism. During and after the withdrawal of thimerosal from numerous vaccinations, many families refused to have their children vaccinated against diseases such as measles, mumps, and rubella due to the increasing rate of neurological disorders found in children post vaccination. In fact, the CDC and AAP made an announcement to withdraw the mercury compound from vaccinations as a precaution due to such trends in 2001.
At the time of the Immunization Safety Review Committee's examination in 2001, not many epidemiological studies were conducted to provide conclusive evidence of a causal relationship. As a result, it was highly recommended to remove thimerosal from vaccines as "a prudent measure in support of the public health goal to reduce mercury exposure of infants and children as much as possible". In fact, they hoped that this state of action would boost the public image of vaccinating more children against childhood diseases.
However, it only led to more suspicion that thimerosal was a possible cause of autism via vaccinations. Many families filed lawsuits in US federal courts to have damages from alleged toxicity in vaccines be compensated. Today, we have had numerous studies performed to reject an association between thimerosal exposure and development of autism. For example, in 2004, a cohort study was conducted in the United Kingdom that showed no support for a causal relationship:
But this popular belief of vaccines causing autism directly still lingers within the population. Many anti-vaccine families had, and still claim, injuries for their children due to vaccines to the U.S. Court of Federal Claims. However, from the thimerosal controversy alone, only a few cases have been compensated for, while the rest have either been denied or are pending, as we have many studies illustrating no concrete evidence to support the vaccine-autism link. In fact, the CDC has compiled a Concerns about Autism webpage with numerous resources and articles dispelling this link.
Of course, it is not just "science" that allows many to draw to this conclusion. The media plays a big role, distorting and exaggerating incidents and facts that may not have been necessarily proven in their entirety. In fact, both the media and the public concerned with this issue contributed to the publication of the Wakefield paper in 1998, an experimental study conducted by British doctor Andrew Wakefield which claimed to establish an association between vaccines and autism incidence among children.
Wakefield addressing supporters at the "vaccination choice" rally in Chicago back in May 2010 with his future goals to further study other causes of autism. He reaches out to the crowd by appealing to the power of choice of whether to vaccine children or not: "does [medicine] serve the patients or the pharmaceutical industry?"
In 1998, Dr. Andrew Wakefield published a paper in the Lancet that started what would become the autism epidemic scare. Previously there had been no evidence supporting an association between the combined measles, mumps, and rubella vaccine and autism. The paper stated that they "identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers." Dr. Wakefield describes a new syndrome of regressive developmental behavior that is most likely a consequence of the development of colitis.
The most significant point was the implication that the MMR vaccine most likely was the cause of this new syndrome, which he called autistic enterocolitis. However, in 2010, The Lancet retracted the paper after it was found that Wakefield mistreated the patients and falsified data. Even though the paper was retracted, the damage it caused still persists today.
The video clip below provides an overview of the Wakefield scandal.
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Andrew Wakefield's paper was the first to imply an association between the MMR vaccine and autism, spurring a public health disaster. Even though all the studies that followed disproved the link, as well as the fact that scientists and physicians unanimously agree that the vaccine is safe, the general public continues to be suspicious of vaccines. As a result of this fear, less and less parents are vaccinating their children, lowering the percentage from 92% to as low as 73% of vaccinations in the UK. This is an issue since the herd immunity threshold for measles is quite high, mostly due to the disease's virulence. For herd immunity against measles, the vaccine coverage needs to stay above 92-94%. As a result of this decrease in vaccine induced immunity, the incidence of measles has significantly increased.
In 1998, before the paper was released, there were only 56 confirmed cases of measles. However, after the paper gained acceptance and less people vaccinated their children with the MMR vaccine, the number of measles cases in 2006 alone was 740. It has continued to increase and the UK has experienced 2,030 confirmed cases of measles in 2012. For the first time in years, measles has been declared endemic in the UK. In addition to this increase, in 2006 a boy became the first person in fourteen years to die of measles in Britain. The US has also experienced the same phenomena, which is where Wakefield currently works and continues to receive thousands of dollars in donations for his cause.
The media plays a vital role in how the public interprets scientific findings. Not everyone knows how to access scientific papers, let alone how to decipher its scientific jargon. So most people come in contact with information through secondary sources, like the media. It is simply more comprehensible and more available to the general public. However, the media, including the Internet, isn't necessarily the best source since it can be biased, and is not subject to peer review.
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The figure above compares the number of scientific papers published per year about the MMR vaccine and the number of new story results on google for MMR+autism searches. In the later years, new stories continued to emerge in the media while there were less reportable scientific publications. |
The grey line in the figure above is taken from Figure 1 (left) and represents the google news reports about MMR+Autism. This graph demonstrates that an increase in the number of new story results on google for MMR and autism correlates with a drop in the MMR immunization rates. |
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It is important to note, that even though Andrew Wakefield is attributed with igniting the anti-vaccine movement, the media is responsible for perpetuating the ideology. This is due to the fact that anti-MMR campaigns are more widely covered, even though their research represents a small minority in comparison to MMR safety campaigns.
Even stories with no scientific background worked to convince the public that the MMR vaccine causes autism. Mothers of children with autism played a large role in the vaccine phobia, since their stories were highly covered by the media. Even without evidence to prove it, the claims that their children were diagnosed with autism after receiving the MMR vaccine resonated throughout the public. Another personal story that gained a fair amount of attention was the one about the Prime Minister, Tony Blair's, son. The Blair's inadvertently made the English more skeptical by refusing to answer if their infant son had received the MMR vaccine. A study in the Economic and Social Research Council found that 32% of all stories that were written about the MMR vaccine spoke of Leo Blair, while Wakefield was only mentioned in 25% of these stories.
In the light of so much research disproving the association, the idea that the MMR vaccine causes autism persists as a result of the media's impact on public perception. The misrepresentation of the scientific data has magnified the public's existing mistrust of vaccines.
After discussing some of the reason's why the MMR-autism association has persisted, it is important to delve into the facts that directly disprove the idea. Several factors inherent to the development of autism work to disprove this link. There are genetic aspects that contribute to the onset of autism, which clearly precede the introduction of the MMR vaccine. Additional factors include the timing of the development of symptoms, as well as prenatal and postnatal biological factors unrelated to the MMR vaccine.
Home-movie studies have shown that symptoms of autism can be observed before twelve, and even four months of age, and children usually receive the MMR vaccine between 12 and 15 months old. This small time period between the onset of ASD symptoms and when the child receives the vaccine contributes to the misguided notion that the MMR vaccine causes autism.
Evidence also shows that ASD can be influenced prenatally. In fact, new studies have observed that environmental factors in the womb might play a greater role in the development in autism than previously thought. Joachim Hallmayer's study on twins has claimed that ASD susceptibility has a moderate genetic heritability and a substantial shared twin environmental component. This is based on the percentage of twin correspondence, in identical and fraternal twins. The study found that the correspondence for identical and fraternal twins were higher. The authors generated several models to predict the effect of several factors, and found that the best fitting model for ASD had a genetic heritability of 38% and a shared environmental variance component of 58%.
Some of the environmental exposures that may increase ASD susceptibility, such as viral or toxic agents, have been identified for some time now. It has been shown to be especially harmful if the fetus is exposed during the 1st and early 2nd trimester.
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The activity below provides examples of some agents that will increase the fetus' chance of developing ASD as a child, based on more recent studies.
This evidence shows how various environmental triggers can significantly increase the risk of a child developing autism, long before they even receive the vaccine. Even though this contributes to the dispute against the association between the MMR vaccine and autism, it is not enough to directly dismiss it. Nevertheless, there have been dozens of studies performed after the Wakefield paper that can more directly disprove the association. One of the more well known papers, is the Brent Taylor paper published in 1999.
In response to the highly controversial paper published by Andrew Wakefield, scientists looked to investigate the most serious implication; that the MMR vaccine was the most likely cause of autism. Two fundamental papers published by Brent Taylor in years following the release of the Wakefield paper aim to investigate the notion that the MMR vaccine is a cause of autism.
Brent Taylor's first paper, published in 1999, was a population based case study that looked at children with autistic disorders who had been born since 1979. This was Taylor's first response to the Wakefield paper that looked to explore the notion that the MMR vaccine was a cause of autism based on statistical analysis.
Taylor extracted information pertaining to the age at the diagnosis of autistic disorder, the age at which parents became concerned about the child's development, and the age at when or if regression became noticeable from 498 cases of autism on the spectrum. With this information, Taylor ran statistical analysis on three associations and the results showed:
Based on statistical analysis of the trend in the time series of cases, the age of diagnosis based on unvaccinated children and vaccinated children, and temporal associations Taylor has shown there is no causal association between the MMR vaccine and autism.
Taylor's second paper, published in 2002, investigates one of Wakefield's main claims that they "identified associated gastrointestinal disease and developmental regression in a group of previously normal children".
The population based study looked at 278 children with core autism and 195 with atypical autism. Taylor reviewed case notes and found main outcome measures, including recorded bowel problems lasting at least three months, age of reported regression of the child's development, and the relation of these to the MMR vaccination was introduced. The results showed:
Based on these results there is no support for an association between the MMR vaccine and developmental regression or bowel problems. The identification of no connection between the MMR vaccine and bowel problems further discredits Wakefield's attempt to legitimize unnecessary medical examinations, previously discussed. Furthermore, discrediting his assertion that the MMR vaccine causes autism.
While Wakefield's paper created a public health crisis even after the paper was criticized by highly recognized scientists, Taylor's research hardly made a dent in comparison. Taylor's research was recognized in the scientific world as being a credible investigation into the notion that the MMR vaccine could cause autism, but the research was not highly publicized through media outlets. This allowed the idea of the MMR vaccine causing autism to continue to be perpetuated by news and media sources inspite of scientific evidence. Not only is the notion influenced by media, but by highly recognized celebrities such as Jenny McCarthy who believes her son developed autism after receiving the MMR vaccine.
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