Is brain injury the cause of Autism?

Leo Kanne introduced the label early infantile autism. Picture source: Johns Hopkins University

Leo Kanne introduced the label early infantile autism. Picture source: Johns Hopkins University

It is intriguing that conditions which clearly have always existed may nonetheless only be recognized and accorded significance relatively late. This is the case with Autism. It was only in 1940 that the first clinical description were provided by Kanner and Asperger (there was published almost simultaneously although, both researchers seem to have been unaware of others work). And it’s certain that severe classical cases of autism occur long before this. Uta Frith and Rab Houston in their recent book AUTISM IN HISTORY, present the most detailed evidence for such a diagnosis in case of a young man living in the 18th century and in their earlier book, Frith Hazarded, the thought that Autism might explain the otherwise almost unintelligible behavior of the Franciscan monk brother Jupiter of the blessed fools of old Russia and so on.

While Asperger regarded autism as organic, a biological defect of effective contact. Kanner saw it as physiological or reactive a reaction to a supposed lack of parental love or care and in particular to a cold “refrigeration Mother” Asperger’s point of view or findings did not become widely known (it was only translated into English in the 1980s and Kanner’ unfortunate formulation was rather widely accepted during the 1950s and 1960s with sometimes dire. Consequences to both autistic children and their parents (Kanner’s psychological theory is still accepted in many parts of the world). But by the late 1900s it had become apparent that autisms was organic, although not a “disease” in visual sense- not.
Specifically a disorder or childhood but rather a disorder of the development of certain parts of the mind and brain and subs, a lifelong condition. Up to this point, approaches had been purely clinical and epidemiological. What was the incidence of autism? What were its causes? How did autism present itself? Ever change with time? What could be done with drugs or behavior? When people refer to“Autism”today, they are usually talking about Autism Spectrum Disorders (ASD), which is a brain- based disorder characterized by social- communication challenges and restricted repetitive behaviors, activities, and interests. The Centers for Disease Control describes ASDs as: “a developmental disability that can cause significant social, communication and behavioral challenges. There is often nothing about how people with ASD look that sets them apart from other people, but people with ASD may communicate, interact, behave, and learn in ways that are different from most other people. The learning, thinking, and problem- solving abilities of people with ASD can range from gifted to severely challenged. Some people with ASD need a lot of help in their daily lives; others need less.”

Autism is about 4.5 times more likely to affect boys than girls, and is found in all racial, ethnic, and social groups. There is no known single cause for autism, although the best available science points to important genetic components. Through twin studies, scientists have determined that autism is a genetically based condition. If one identical (monozygotic) twin has autism then there is a 36-95% chance that the other twin will also be diagnosed with an autism spectrum disorder. For non-identical (dizygotic) twins, the chance is about 0-31% that both twins will develop autism spectrum disorder. The chance that siblings will both be affected by ASD is also about 2-18%.
Scientists are unsure what, if any, environmental triggers may be involved in autism. One theory, popular in the late 1990’s and early 2000’s, that vaccines cause autism has since been disproven by numerous studies conducted around the world.
Autism Spectrum Disorders are characterized by significant impairments in social interaction and communication skills, as well as by the presence of extremely challenging behaviors. Such behaviors include repetitive motor behaviors (hand flapping, body rocking), insistence on sameness, resistance to change and in some cases, aggression or self-injury.
Many individuals with an autism spectrum disorder have significant cognitive impairments, although some have typical or even above average IQs. 30-50% of people with autism also have seizures.
Dr. Leo Kanner first described autism in 1943. He reported on eleven children who showed a marked lack of interest in other people, but a highly unusual interest in the inanimate environment. Initially, autism was thought to be an early form of schizophrenia, which led to the belief that its onset could be caused by negative experience or bad parenting. We now know that this is not the case.
Autism spectrum disorder (ASD) and autism are both general terms for a group of complex disorders of brain development. These disorders are characterized, in varying degrees, by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. With the May 2013 publication of the DSM-5 diagnostic manual, all autism disorders were merged into one umbrella diagnosis of ASD. Previously, they were recognized as distinct subtypes, including autistic disorder, childhood disintegrative disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS) and Asperger syndrome.
ASD can be associated with intellectual disability, difficulties in motor coordination and attention and physical health issues such as sleep and gastrointestinal disturbances. Some persons with ASD excel in visual skills, music, math and art.
Autism appears to have its roots in very early brain development. However, the most obvious signs of autism and symptoms of autism tend to emerge between 2 and 3 years of age. Autism Speaks continues to fund research on effective methods for earlier diagnosis, as early intervention with proven behavioral therapies can improve outcomes.
Increasing autism awareness is a key aspect of this work and one in which our families and volunteers play an invaluable role.

How common is Autism:
Autism statistics from the U.S. Centers for Disease Control and Prevention (CDC) identify around 1 in 68 American children as on the autism spectrum–a ten-fold increase in prevalence in 40 years.
Careful research shows that this increase is only partly explained by improved diagnosis and awareness. Studies also show that autism is four to five times more common among boys than girls. An estimated 1 out of 42 boys and 1 in 189 girls are diagnosed with autism in the United States.
ASD affects over 3 million individuals in the U.S. and tens of millions worldwide. Moreover, government autism statistics suggest that prevalence rates have increased 10 to 17 percent annually in recent years. There is no established explanation for this continuing increase, although improved diagnosis and environmental influences are two reasons often considered.

Autism symptoms and signs

Brain structure implicated in Autism - Image source: National Institutes of Mental Health

Brain structure implicated in Autism – Image source: National Institutes of Mental Health

· Abnormal Body Posturing or Facial Expressions.
· Abnormal Tone of Voice.
· Avoidance of Eye Contact or Poor Eye Contact.
· Behavioral Disturbances.
· Deficits in Language Comprehension.
· Delay in Learning to Speak.
· Flat or Monotonous Speech.
· Inappropriate Social Interaction.

Causes of Autism
Not long ago, the answer to this question would have been “we have no idea.” Research is now delivering the answers.
First and foremost, we now know that there is no one cause of autism just as there is no one type of autism. Over the last five years, scientists have identified a number of rare gene changes, or mutations, associated with autism. A small number of these are sufficient to cause autism by themselves.
Most cases of autism, however, appear to be caused by a combination of autism risk genes and environmental factors influencing early brain development.
In the presence of a genetic predisposition to autism, a number of nongenetic, or “environmental,”stresses appear to further increase a child’s risk.
The clearest evidence of these autism risk factors involves events before and during birth. They include advanced parental age at time of conception (both mom and dad), maternal illness during pregnancy and certain difficulties during birth, particularly those involving periods of oxygen deprivation to the baby’s brain.
It is important to keep in mind that these factors, by themselves, do not cause autism. Rather, in combination with genetic risk factors, they appear to modestly increase risk.
A growing body of research suggests that a woman can reduce her risk of having a child with autism by taking prenatal vitamins containing folic acid and/or eating a diet rich in folic acid (at least 600 mcg a day) during the months before and after conception.
Increasingly, researchers are looking at the role of the immune system in autism.
Autism Speaks is working to increase awareness and investigation of these and other issues, where further research has the potential to improve the lives of those who struggle with autism. Also, Experts are still uncertain about all the causes of autism. In all likelihood, there are multiple causes- rather than just one. It appears to be
that a number of different circumstances- including environmental, biologic, and genetic factors- set the stage for autism and make a child more likely to have the disorder.
There is reason to believe that genes play a major role in the development of autism. It has been found that identical twins are more likely to both be affected than twins who are fraternal (not genetically identical). In a family with one autistic child, the chance of having another child with autism is about 5 percent- or one in 20- much higher than in the normal population.
Sometimes, parents or other relatives of an autistic child have mild social impairments (such as repetitive behaviors and social or communication problems) that look very much like autism. Research also has found that some emotional disorders (such as manic depression) occur more often in families of a child with autism.
At least one group of researchers has found a link between an abnormal gene and autism. The gene may be just one of three to five or more genes that interact in some way to cause the condition. Scientists suspect that a faulty gene or genes might make a person more likely to develop autism when there are also other factors present, such as a chemical imbalance, viruses or chemicals, or a lack of oxygen at birth.
In a few cases, autistic behavior is caused by:
§ Rubella (German measles) in the pregnant mother.
§ Tuberous sclerosis (a rare genetic disorder that causes benign tumors to grow in the brain as well as in other vital organs).
§ Fragile X syndrome (the most common inherited form of intellectual disability).
§ Encephalitis (brain inflammation).
§ Untreated phenylketonuria (PKU) – when the body lacks an enzyme needed for normal metabolism.
In the past se , there has been interest in a theory that suggested a link between autism and the use of thimerosal, a mercury-based preservative used in the measles-mumps-rubella (MMR) vaccine. Although mercury is no longer found in childhood vaccines in the United States, some parents still have concerns about vaccinations.
However, many well-done, large-scale studies have now been performed that have failed to show a link between thimerosal and autism. A panel from the Institute of Medicine is now examining these studies. The reports include a large Danish study that concluded that there was no causal relationship between childhood vaccination using thimerosal-containing vaccines and the development of an autism spectrum disorder and a U.S. study looking at exposure to mercury, lead, and other heavy metals. Both the American Academy of Pediatrics and the Centers for Disease Control and Prevention assert that there is no link between autism and the MMR vaccine or any other vaccine.
Other potential causes of autism are environmental toxins, including pesticides and heavy metals such as mercury. Heavy metals are certainly more commonly encountered in the environment now than they were in the past. It may be that people with autism or those at higher risk for developing it are more sensitive than others to these toxins.

Related disorders
Autism involves atypical brain development which often becomes apparent in behavior and social development before a child is three years old. It can be characterized by impairments in social interaction and communication, as well as restricted interests and stereotyped behavior, and the characterization is independent of any underlying neurological defects. Other characteristics include repetitive-like tasks seen in their behavior and sensory interests.
This article uses the terms autism and ASD to denote classical autism and the wider dispersion of symptoms and manifestations of autism, respectively.
Autism’s theory of causation is incomplete. It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism’s characteristic triad of symptoms. However, there is increasing suspicion among researchers that autism does not have a single cause, but is instead a complex disorder with a set of core aspects that have distinct causes. Different underlying brain dysfunctions have been hypothesized to result in the common symptoms of autism, just as completely different brain problems result in intellectual disability. The terms autism or ASDs capture the wide range of disease processes at work.
Although these distinct causes have been hypothesized to often co-occur, it has also been suggested that the correlation between the causes has been exaggerated. The number of people known to have autism has increased dramatically since the 1980s, at least partly due to changes in diagnostic practice. It is unknown whether prevalence has increased as well.
The consensus among mainstream autism researchers is that genetic factors predominate. Environmental factors that have been claimed to contribute to autism or exacerbate its symptoms, or that may be important to consider in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs and vaccines. Among these factors, vaccines have attracted much attention, as parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and parental concern about vaccines has led to a decreasing uptake of childhood immunizations and an increasing likelihood of measles outbreaks. However, there is overwhelming scientific evidence showing no causal association between the measles-mumps-rubella (MMR) vaccine and autism, and there is no scientific evidence that the vaccine preservative thimerosal causes autism.

Genetic factors may be the most significant cause for autism spectrum disorders. Early studies of twins had estimated heritability to be over 90%, meaning that genetics explains over 90% of whether a child will develop autism. However, this may be an overestimation, as new twin studies estimate the heritability at between 60-90%.
Many of the non-autistic co-twins had learning or social disabilities. For adult siblings the risk for having one or more features of the broader autism phenotype might be as high as 30%.
However, in spite of the strong heritability, most cases of ASD occur sporadically with no recent evidence of family history. It has been hypothesized that spontaneous de novo mutations in the father’s sperm or mother’s egg contribute to the likelihood of developing autism. There are two lines of evidence that support this hypothesis. Firstly, individuals with autism have significantly reduced fecundity, they are 20 times less likely to have children than average, thus curtailing the persistence of mutations in ASD genes over multiple generations in a family.
Secondly, the likelihood of having a child develop autism increases with advancing paternal age, and mutations in sperm gradually accumulate throughout a man’s life.
The first genes to be definitively shown to contribute to risk for autism were found in the early 1990s by researchers looking at gender-specific forms of autism caused by mutations on the X chromosome. An expansion of the CGG trinucleotide repeat in the promoter of the gene FMR1 in boys causes fragile X syndrome, and at least 20% of boys with this mutation have behaviors consistent with autism spectrum disorder.
Mutations that inactivate the gene MECP2 cause Rett syndrome, which is associated with autistic behaviors in girls, and in boys the mutation is embryonic lethal.
Besides these early examples, the role of de novo mutations in ASD first became evident when DNA microarray technologies reached sufficient resolution to allow the detection of copy number variation (CNV) in the human genome CNVs are the most common type of structural variation in the genome, consisting of deletions and duplications of DNA that range in size from a kilobase to few megabases. Microarray analysis has shown that de novo CNVs occur at a significantly higher rate in sporadic cases of autism as compared to the rate in their typically developing siblings and unrelated controls. A series of studies have shown that gene disrupting de novo CNVs occur approximately four times more frequently in ASD than in controls and contribute to approximately 5-10% of cases.
Based on these studies, there are predicted to be 130-234 ASD-related CNV loci. The first whole genome sequencing study to comprehensively catalog de novo structural variation at a much higher resolution than DNA microarray studies has shown that the mutation rate is approximately 20% and not elevated in autism compared to sibling controls. However, structural variants in individuals with autism are much larger and four times more likely to disrupt genes, mirroring findings from CNV studies.
CNV studies were closely followed by exon sequencing studies, which sequence the 1-2% of the genome that codes for proteins (the “exon”). These studies found that de novo gene inactivating mutations were observed in approximately 20% of individuals with autism, compared to 10% of unaffected siblings, suggesting the etiology of ASD is driven by these mutations in around 10% of cases. There are predicted to be 350-450 genes that significantly increase susceptibility to ASDs when impacted by inactivating de novo mutations. A further 12% of cases are predicted to be caused by protein altering missense mutations that change an amino acid but do not inactivate a gene. Therefore approximately 30% of individuals with autism have a spontaneous de novo large CNV that deletes or duplicates genes, or mutation that changes the amino acid code of an individual gene. A further 5-10% of cases have inherited structural variation at loci known to be associated with autism, and these known structural variants may arise de novo in the parents of affected children.
Tens of genes and CNVs have been definitively identified based on the observation of recurrent mutations in different individual and suggestive evidence has been found for over 100 others. The Simons Foundation Autism Research Initiative (SFARI) details the evidence for each genetic locus associated with autism.
These early gene and CNV findings have shown that the cognitive and behavioral features associated with each of the underlying mutations is variable. Each mutation is itself associated with a variety of clinical diagnoses, and can also be found in a small percentage of individuals with no clinical diagnosis. Thus the genetic disorders that comprise autism are not autism-specific. The mutations themselves are characterized by considerable variability in clinical outcome and typically only a subset of mutation carriers meet criteria for autism. This variable expressivity results in different individuals with the same mutation varying considerably in the severity of their observed particular trait.
The conclusion of these recent studies of de novo mutation is that the spectrum of autism is breaking up into quanta of individual disorders defined by genetics.

Epigenetic mechanisms may increase the risk of autism. Epigenetic changes occur as a result not of DNA sequence changes but of chromosomal histone modification or modification of the DNA bases. Such modifications are known to be affected by environmental factors, including nutrition, drugs and mental stress. Interest has been expressed in imprinted regions on chromosomes 15q and 7q.

Prenatal enviroment
The risk of autism is associated with several prenatal risk factors, including advanced age in either parent, diabetes, bleeding or use of psychiatric drugs in the mother during pregnancy.
Autism has been linked to birth defect agents acting during the first eight weeks from conception, though these cases are rare.

Infectious processes

Prenatal viral infection has been called the principal non-genetic cause of autism. Prenatal exposure to rubella or cytomegalovirus activates the mother’s immune response and greatly increases the risk for autism.
Congenital rubella syndrome is the most convincing environmental cause of autism. Infection-associated immunological events in early pregnancy may affect neural development more than infections in late pregnancy, not only for autism, but also for psychiatric disorders of presumed neuro developmental origin, notably schizophrenia.

Environmental Agents
Teratogens are environmental agents that cause birth defects. Some agents that are theorized to cause birth defects have also been suggested as potential autism risk factors, although there is little to no scientific evidence to back such claims. These include exposure of the embryo to valproic acid, thalidomide or misoprostol. These cases are rare.
Questions have also been raised whether ethanol (grain alcohol) increases autism risk, as part of fetal alcohol syndrome or alcohol-related birth defects. All known teratogens appear to act during the first eight weeks from conception, and though this does not exclude the possibility that autism can be initiated or affected later, it is strong evidence that autism arises very early in development.

Other maternal conditions
Thyroid problems that lead to thyroxin deficiency in the mother in weeks 8–12 of pregnancy have been postulated to produce changes in the fetal brain leading to autism.
Thyroxin deficiencies can be caused by inadequate iodine in the diet, and by environmental agents that interfere with iodine uptake or act against thyroid hormones. Possible environmental agents include flavonoids in food, tobacco smoke, and most herbicides. This hypothesis has not been tested.
Diabetes in the mother during pregnancy is a significant risk factor for autism; a 2009 meta- analysis found that gestational diabetes was associated with a twofold increased risk. A 2014 review also found that maternal diabetes was significantly associated with an increased risk of ASD. Although diabetes causes metabolic and hormonal abnormalities and oxidative stress, no biological mechanism is known for the association between gestational diabetes and autism risk.
Maternal obesity during pregnancy may also increase the risk of autism, although further study is needed.

How is Autism T=treated
Each child or adult with autism is unique and so, each autism intervention plan should be tailored to address specific needs.
Intervention can involve behavioral treatments, medicines or both. Many persons with autism have additional medical conditions such as sleep disturbance, seizures and gastrointestinal (GI) distress. Addressing these conditions can improve attention, learning and related behaviors.
Early intensive behavioral intervention involves a child’s entire family, working closely with a team of professionals. In some early intervention programs, therapists come into the home to deliver services. This can include parent training with the parent leading therapy sessions under the supervision of the therapist.
Other programs deliver therapy in a specialized center, classroom or preschool. Typically, different interventions and supports become appropriate as a child develops and acquires social and learning skills.
As children with autism enter school, for example, they may benefit from targeted social skills training and specialized approaches to teaching.
Adolescents with autism can benefit from transition services that promote a successful maturation into independence and employment opportunities of adulthood.

What early intervention therapies are currently available?

Objective scientific studies have confirmed the benefits of two methods of comprehensive behavioral early intervention. They are:
1. The Lovaas Model based on Applied Behavior Analysis (ABA) and
2. The Early Start Denver Model.
Parents and therapists also report success with other commonly used behavioral therapies, including Floor time, Pivotal Response Therapy and Verbal Behavior Therapy.

Treatment options for toddlers and preschool children
Scientific studies have demon intervention early intensive behavioral intervention improves learning, communication and social skills in young children with autism.
While the outcomes of early intervention vary, all children benefit. Researchers have developed a number of effective early intervention models. They vary in details, but all good early intervention programs share certain features. They include:
√ The child receives structured, therapeutic activities for at least 25 hours per week.
√ Highly trained therapists and/or teachers deliver the intervention. Well- trained paraprofessionals may assist with the intervention under the supervision of an experienced professional with expertise in autism therapy.
√ The therapy is guided by specific and well-defined learning objectives and the child’s progress in meeting these objectives is regularly evaluated and recorded.
√ The intervention focuses on the core areas affected by autism. These include social skills, language and communication, imitation, play skills, daily living and motor skills.
√ The program provides the child with opportunities to interact with typically developing peers.
√ The program actively engages parents in the intervention, both in decision making and the delivery of treatment.
√ The therapists make clear their respect for the unique needs, values and perspectives of the child and his or her family.
√ The program involves a multidisciplinary team that includes, as needed, a physician, speech-language pathologist and occupational therapist.

Do children or adults diagnosed with Autism ever move off “The Spectrum”?

Growing evidence suggests that a small minority of persons with autism progress to the point where they no longer meet the criteria for a diagnosis of autism spectrum disorder (ASD). Various theories exist as to why this happens. They include the possibility of an initial misdiagnosis, the possibility that some children mature out of certain forms of autism and the possibility that successful treatment can, in some instances, produce outcomes that no longer meet the criteria for an autism diagnosis.
You may also hear about children diagnosed with autism who reach “best outcome” status. This means they have scored within normal ranges on tests for IQ, language, adaptive functioning, school placement and personality, but still have mild symptoms on some personality and diagnostic tests.
Some children who no longer meet the criteria for a diagnosis of autism spectrum disorder are later diagnosed with attention deficit and hyperactivity disorder (ADHD), anxiety disorder or a relatively high-functioning form of autism such as Asperger Syndrome.
Currently, we don’t know what percentage of persons with autism will progress to the point where they “lose their diagnosis.” We likewise need further research to determine what genetic, physiological or developmental factors might predict who will achieve such outcomes.
We do know that significant improvement in autism symptoms is most often reported in connection with intensive early intervention- though at present, we cannot predict which children will have such responses to therapy.
We also know that many people with autism go on to live independent and fulfilling lives, and that they all deserve the opportunity to work productively, develop meaningful and fulfilling relationships and enjoy life. With better interventions and supports available, those affected by autism are having better outcomes in all spheres of life.

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Oloruntoba Fisayo (O’fisayo),
400 level, Physiology Department,
Ladoke Akintola University Of Technology

Author: Faisol Oladosu

Faisol - founder of

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