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Autism Spectrum Disorders – Part 1 Characteristics of ASD

INTRODUCTION

Autism Spectrum Disorders (ASD) encompass a group of developmental disorders

whose symptoms range on a continuum that runs from mild to severe in expression [1].

ASD is typically present early in life, anytime from infancy or early childhood; however,

in the new DSM-V, there are changes in place for diagnostic age criteria in that deficits

from ASD may not be detected until later on in life. This later detection may result from

lower social demands placed on an individual as a result of assistance from parents or

caregivers earlier on in life.

The onset of ASD has been intensively studied [2-4], and it is largely accepted that the

time of diagnosis may occur far after the time of onset. Additionally, the time between

where parents indicate that the child shows early signs or symptoms of ASD or

abnormal development and the time until diagnosis may be quite lengthy. It is important

to note here that detecting early signs of ASD has been indicated to be quite difficult [5].

This is why ASD is sometimes only diagnosed once a child is put into situations that

require social abilities, and a lack is seen in these situations.

More than 500,000 people in the United States have some form of diagnosed autism [6].

Autism may keep a child from forming effective relationships with other people, due in

part to an inability to properly interpret facial expressions or emotions. Children with

autism spectrum disorders may be resistant to cuddling or change, and they may play

alone or have delays in speech development. People with autism also frequently repeat

body movements or have extreme attachments to certain objects. However, there are

positive aspects to autism, such as the fact that many people with autism excel on

certain mental levels, such as counting and measuring, or at art, music, or memory.

The precise causes of ASD are not known. However, it is known that genetic factors

play a role in ASD. It is also known that non-genetic, environmental factors play a role in

the development of ASD. It is thought that ASD is the result of a combination of genetic


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and non-genetic factors. What basically happens is that non-genetic, environmental

factors come into play to make those who are genetically susceptible to ASD more likely

to develop ASD. ASD may then develop gradually, or the individual may experience

what is known as regression, where he or she may lose some or all of their acquired

skills. The loss of skills can happen suddenly or gradually. Overall, there are a number

of risk factors for ASD, including gender – boys are more likely than are girls to develop

ASD – genetics, certain prenatal and perinatal factors, neuroanatomical abnormalities

such as enlargement of the brain, and environmental factors.

There is no cure for ASD. The primary goals of ASD treatments are to lessen deficits

and to lessen family stresses. There are a number of ways to do these things, including

applied behavioral therapy, structured teaching, speech and language therapy, social

skills therapy, occupational therapy, and the use of medication. Additionally, educating

parents, caregivers, and siblings and providing these individuals with ways to cope with

the unique challenges that having an individual with ASD in the household brings helps

in alleviating the inevitable resulting family stress.

INCLUDED DISORDERS

Autism

The American Psychiatric Association has put forth a

new definition for autism as a part of the revisions made

for the new Diagnostic and Statistical Manual of Mental

Disorders (DSM). Autism will be seen as part of a

continuum of disorders termed autism spectrum disorder,

involving a range of disorders, such as autistic disorder,

Asperger’s syndrome, childhood disintegrative disorder,

and pervasive developmental disorder not otherwise specified. Dr. James Scully of the

APA has stated that the criteria will “lead to more accurate diagnosis and will help

physicians and therapists design better treatment interventions” [8].

[7]

[7]


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Autistic disorder is also known as autism or mindblindness. This disorder generally

presents sometime in the first three years of life, and the child appears to live within its

own world. The child also appears to show little interest in other people and displays

poor social skills. The focus of a child with autistic disorder is on a consistent routine,

with repetitive odd or peculiar behaviors. Children with autism frequently have problems

communicating, and they often will avoid making eye contact with others or will avoid

attaching to others.

Autistic disorder may be associated with a number of infirmities, including difficulties

with motor coordination and attention, intellectual disability, and physical health issues

such as gastrointestinal issues or sleep issues. However, despite difficulties, some

people with autistic disorder often excel in music, art, math, or with visual skills.

Autistic disorder seems to have roots in the early development of the brain, although the

most obvious signs and symptoms emerge between 2 – 3 years of age. Approximately

1 out of every 88 children in the United States will have an ASD; this has been a huge

increase in prevalence over the past 40 years. The increase is due in part to

improvements made in diagnostic tools as well as disease awareness. Another reason

for the increase may be environmental influence. Autistic disorder is much more

common in boys than it is in girls: approximately 1 out of every 54 boys and 1 out of

every 252 girls is diagnosed with an ASD in the U.S., with ASD affecting over 2 million

individuals in the U.S., and millions are affected worldwide.

There is no one cause for ASD, although a genetic predisposition appears to play a

role, as do environmental, or non-genetic, factors. Most cases of ASD appear to be the

result of a combination of both genetic and non-genetic factors, with environmental

stressors increasing the risk of development of ASD in children who already have a

genetic predisposition. The clearest evidence of these types of risk factors includes

events that happen before or during birth, such as maternal illness or birthing difficulties.

Asperger Syndrome


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Asperger Syndrome is considered a sub-type of autism spectrum disorder. The cause of

Asperger Syndrome is unknown, and presents 4 times more frequently in boys than it

does in girls [9].

Many consider Asperger syndrome to be the mildest form of autism; therefore, many

with Asperger’s are considered to be the highest functioning autistic individuals.

However, even though many individuals with Asperger’s may be high functioning, they

still share certain key symptoms with others who suffer from autism spectrum disorders,

such as a lack of normal social conversation, lack of normal eye contact, deficits in body

language and facial expression, and difficulties in maintaining social relationships.

Those with Asperger syndrome also frequently engage in repetitive behaviors and may

become excessively attached to objects or routines.

The prevalence of Asperger syndrome is not well known. It is not even well recognized

prior to the age of 5 or 6, primarily because the individual has normal language

development. Asperger syndrome occurs in all ethnic groups and affects every age

group [10]. Additionally, it does not just affect the child during childhood; studies indicate

that children who suffer from Asperger syndrome carry their problems with them into

adulthood and some develop further psychiatric problems in adulthood.

Some of the common signs or symptoms of those with Asperger syndrome are having

monotone speech or lack of rhythm in speaking. Additionally, an individual with

Asperger syndrome may have problems modulating the volume in his or her voice and

may need to be continually reminded to talk more softly. Individuals with Asperger’s are

not generally isolated from the rest of the world as a result of their own withdrawal, but

rather they are isolated because they have poor social skills or because their interests

are narrow. For example, they may approach conversations by speaking only about

their own very narrow interests, making a normal conversation difficult.

Current research [10] indicates that brain abnormalities may be to blame, as some

research has indicated that those children who have Asperger syndrome have

differences in structure and function than do those children who are not affected.


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Researchers posit that these differences could be caused by an abnormal migration of

embryonic cells that in turn affects brain structure in early childhood. This then goes on

to affect the brain circuitry that affects thought and behavior. Scientists have also

suspected that there is a strong genetic component to Asperger syndrome, although no

specific gene for Asperger syndrome has ever been identified. Recent research has

indicated that Asperger syndrome is most likely the result of a grouping of genes in

which variations or deletions cause the individual to become vulnerable to the

development of Asperger syndrome. When combined with environmental factors, this

also determines the severity and the specific symptoms that each individual suffers.

Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) is sometimes

simply called pervasive developmental disorder, or may be used interchangeably with

autism spectrum disorder. There are some health professionals who refer to PDD-NOS

as sub threshold autism. PDD-NOS is a relatively new diagnosis, having been around

for only about 15 years. PDD-NOS is the diagnosis that has come to be commonly

applied to those who are on the autism spectrum but do not generally meet the criteria

for some other autism spectrum disorder in full, such as Asperger Syndrome.

Defining features of PDD-NOS are challenges in language development and social

functioning. Repetitive behaviors are frequently seen with PDD-NOS. Not all children

with PDD-NOS have the same symptoms. Symptoms may sometimes be mild, where

the individual exhibits only a few symptoms while at home or at school. Other

individuals may exhibit severe symptoms in all areas of their lives but still may not

qualify for a diagnosis of autistic disorder.

The signs and symptoms of PDD-NOS are divided into several categories, as outlined

below:

Social Signs and Symptoms:

Children with PDD-NOS have a desire to make and have friends, but they have

no idea how to make that happen. If there are language delays this may hinder


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the ability to socialize with other people. There is frequently difficulty in

understanding body language, tone of voice, and facial expression in others, as

well as difficulty understanding emotions. Children with PDD-NOS often have

trouble distinguishing between emotions such as sadness, happiness and anger.

Communication Signs and Symptoms:

Those with PDD-NOS frequently have language or communication issues. Those

with PDD-NOS may not babble as babies. They also frequently take language

literally and do not have an understanding of things such as sarcasm or joking

language. It is easier to expand language skills in those children who have some

language skills than it is in those children who are entirely nonverbal.

Behavioral Signs and Symptoms:

Children with PDD-NOS may exhibit tantrums or emotional outbursts. These

children may also have a great need for routine. Additionally, individuals with

PDD-NOS can often misinterpret what is happening in a situation and in turn

become easily frustrated. Tantrums are the result of fear and anxiety. Another

common behavioral symptom is perseveration, which means the child will tend to

dwell on certain events or subjects. Individuals with PDD-NOS may become

fixated on one topic or play only with one toy that is associated with a particular

area.

Given the newness of this diagnosis, there has been some disagreement on how to

apply a diagnosis of PDD-NOS. Recently, some studies [11] have suggested that PDD-

NOS may best be utilized by placing individuals into one of three subgroupings of

diagnosis, as explained below:

High functioning PDD-NOS:

This involves approximately 25% of those with PDD-NOS); and, these individuals

generally have symptoms that overlap Asperger’s, but they may differ slightly in

that they have delays in language development or slight cognitive impairment.

Mid-function PDD-NOS:


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This involves approximately 25% of those with PDD-NOS; and, these individuals

generally have symptoms that resemble those with autistic disorder.

Low function PDD-NOS:

This involves approximately 50% of those with PDD-NOS; and, these individuals

meet all of the criteria for autistic disorder, however, some of their symptoms are

noticeably mild.

Another way to diagnose PDD-NOS may be by placing individuals into one of five

subgroupings [12]:

Atypical autism: this category is for young children who may not have developed

a full-blown autistic disorder yet; these are individuals who almost, but not quite,

meet the criteria for autistic disorder.

Residual autism: this category is for individuals who have a history of having

autistic disorder yet may not at present meet the criteria; they therefore still have

some autistic features but as a result of interventions or development they do not

meet the criteria for autistic disorder.

Atypical Asperger syndrome: this category is for young children who may not

have developed full-blown Asperger syndrome as well as for individuals who are

almost, but not quite, to the point of meeting the full criteria for Asperger

syndrome.

Mixed clinical features of atypical Asperger syndrome: this category is for

children with an atypical autistic disorder.

Comorbid autism: this category is for children who have a medical or neurological

disorder, such as tuberous sclerosis, that is associated with some ASD-like

features.

Those who have PDD-NOS respond best to combined therapies. Therapies that have

been demonstrated to work well on PDD-NOS are applied behavioral analysis (ABA),

sensory integration therapy, play therapy, and social skills training. It is important for the

practitioner to pay attention to the child who may not be as easily diagnosed; the Yale


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Developmental Disabilities Clinic [13] indicates that children who have PDD-NOS may

not get the treatment they need as easily as do those diagnosed with autistic disorder.

Additionally, many education systems in the United States do not have a special

education category for those individuals who have PDD-NOS, leaving these individuals

to be placed into programs designed for students with other problems, such as

intellectual disabilities, emotional disturbances, or behavior disorders. This can lead to

the individual getting lost in the crowd and not having their needs met. It is therefore

essential that the practitioner work closely with parents and caregivers to ensure that

the individual with PDD-NOS is getting his or her needs met in all areas.

Childhood Disintegrative Disorder

Childhood disintegrative disorder (CDD), also called Heller’s syndrome, is a condition

wherein children develop normally until approximately age 3 or 4. They then lose all of

the skills they have learned. This includes motor, language, social, and other skills. To

be diagnosed with CDD the child must lack or lose normal function in at least two

developmental skills areas that include: social interaction, communication, and repetitive

or stereotyped patterns of interest and behavior/activities. CDD may be caught at

developmental screenings performed at well-child check-ups; these screenings should

always be performed, although parents should also be encouraged to voice concerns

about their child’s development at other times as well. The cause of CDD is not known,

but a link to the brain and nervous system has been made [14].

Symptoms of CDD include the following: a delay or lack of language, impaired

nonverbal behavior, an inability to start or to maintain conversation, failure to play, loss

of control of the bladder or bowels, loss of previously established language or

communication skills, loss or motor or skills, and; problems forming relationships with

others have been identified. The loss of skills may occur abruptly or it may occur over a

period of time that is extended. Parents should express concerns to a practitioner when

a child loses any developmental skill, whether it is gradual or sudden loss.


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Outcome for CDD is poor. Many children with CDD are as severely impaired as those

with severe autistic disorder. Those with CDD almost always need support for the

duration of their lifetime and may need residential care in facilities such as group homes

or long-term care residential living. There is no cure for CDD, although there are some

treatments that may be used to lessen or relieve symptoms. These treatments include

the following:

Medication:

While there are not any medications that treat this disorder directly, some

medications may be used to treat the behaviors that result, such as anxiety or

depression. Additionally, epilepsy is highly co-occurring with CDD, and

anticonvulsant drugs may be utilized to control seizures.

Behavior therapy:

Behavior therapy programs are frequently utilized to help the individual with ASD

learn language or to help minimize language loss, as well as social skills and

self-care skills. Behavioral therapy programs use systems of reward and

discipline to reinforce behavior that is desirable and to discourage behavior that

is not desirable. It is important that the approach in behavior therapy is consistent

among all practitioners, caregivers, and teachers.

Rett Syndrome

Rett Syndrome is a neurodevelopmental disease that is seen almost entirely in females,

although it may sometimes rarely be seen in males. Rett Syndrome presents in infancy

or early childhood, and is caused by a mutation in the MECP2 gene on the X

chromosome [15]. Since boys have a different combination of chromosomes than do

females, males who have the mutation that causes the syndrome are generally affected

in ways that are devastating. Many die prior to birth or very early in infancy.

Symptoms vary in type and severity. Generally the child may appear to be developing

normally, up until about 6 months of age, and then symptoms begin to appear. This is

also when the rate of growth of the head as well as progress of certain skills such as

communication may start to slow. The most notable changes usually occur at around 12


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– 18 months and occur over weeks to months. There are a number of signs and

symptoms that occur with Rett syndrome, including those listed below:

Slowed growth: the brain slows in growth following birth. One of the first signs

that a child has Rett syndrome is that the child has a smaller than usual head

size. Then, as the child ages, it becomes evident that there are delays in growth

in other body parts as well.

Loss of normal coordination and movement: the individual begins to lose a

significant amount of motor skills. This generally begins between 12 to 18 months

of age and includes a decreased ability to control the hands as well as a

decreased ability to crawl and walk in a normal way. This occurs rapidly at first

and then continues in a more gradual manner.

Loss of communication and the ability to think: individuals who have Rett

syndrome will lose their ability to communicate as well as to speak. They may

also become uninterested in toys, in people, and in their surroundings. The

change may be rapid in some children; for example, some children may

experience a sudden loss of their speech skills. Most children regain skills such

as eye contact over time as well as develop skills such as nonverbal

communication.

Abnormal hand movements: children who have Rett syndrome have stereotyped

hand patterns individual to each child; these may include wringing, clapping,

rubbing, squeezing, or tapping.

Unusual eye movements: those with Rett syndrome may have eye movements

that are unusual, such as blinking, staring intensely, or closing one eye.

Breathing problems: individuals with Rett syndrome may have breathing

problems that include apnea, forceful exhalation of air (or saliva), or rapid

breathing that is abnormal. These types of problems are likely to occur during

waking hours but not during sleep hours.

Irritability: Rett syndrome may cause individuals to become more and more

irritable and agitated as they age, having spells of screaming that can begin

suddenly and last for hours.


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Abnormal behaviors: abnormal behaviors may include sudden and odd facial

expressions or extended bouts of screaming or laughter that occurs for no

reason. Abnormal behaviors also include such behaviors as hand licking or

grasping clothing or hair.

Seizures: many who have Rett syndrome also experience seizures at some point

in their lifetime. The symptoms of these seizures vary, but they can range from

having a periodic muscle spasm to being struck with full-blown epilepsy.

Abnormal spinal curvature: this is also known as scoliosis. Scoliosis commonly

co-occurs with Rett syndrome, and generally begins at around 8 – 11 years of

age.

Irregular heartbeat, or dysrhythmia: many individuals with Rett syndrome

experience this life-threatening issue.

Constipation: constipation is a common issue for those who suffer from Rett

syndrome.

Rett syndrome is generally divided into 4 stages:

Stage I: In this stage the signs and symptoms of the disease may be easily

overlooked, as this stage begins between 6 – 18 months of age. Children who

are in this stage may begin to show less eye contact or begin to lose interest in

their toys. There may also be delays in sitting up or in crawling.

Stage II: Stage II occurs between 1 – 4 years of age. In this stage the child

begins to lose his or her speaking ability as well as the ability to use his or her

hands. Additionally, repetitive and purposeless hand motions begin. Some

children also start to hyperventilate or hold their breath as well as cry or scream

for no reason. It is also frequently difficult for the child to move on his or her own.

Stage III: Stage III is considered a plateau that starts between 2 – 10 years of

age. This stage may last for years. Even though issues with movement may

continue, behavior can improve. Children in this stage frequently cry less often,

and become less irritable.


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Stage IV: This last stage shows extremely reduced mobility as well as muscle

weakness and scoliosis. Communication skills, understanding, and hand skills

usually won’t decline any further in this stage.

Most people who suffer from Rett Syndrome require daily assistance with everyday

tasks. They can usually live moderately long lives, extending to 50 years of age or

longer.

EARLY ETIOLOGY

The precise causes of ASD are not known. However, many think that it is a complex

combination of genetic and environmental components that cause ASD symptoms.

ASD causes may be described in two ways: [16]

Primary ASD, which is also known as idiopathic ASD. This means that there is no

underlying medical condition, which can explain why there are symptoms of ASD.

Ninety percent of all ASD cases are primary ASD.

Secondary ASD, which means that there is an underlying medical condition that is

thought to be responsible – or at the very least, partially responsible – for the ASD

symptoms. Ten percent of all ASD cases are secondary ASD.

Primary ASD

Researchers have examined four possible causes to primary ASD. These causes are

outlined below:

Genetic causes:

There are certain genetic mutations, which may lead to a child being more likely to

develop ASD. ASD has been known to run in families, and there is 5 – 6% likelihood

that younger children born into families with an older child with ASD will also themselves

have ASD. Identical twins are also at risk for developing ASD. For example, if one twin

develops ASD, there is 60% likelihood that the other will develop ASD as well. However,

it is important to note that there are currently no specific genes that have been linked to


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the development of ASD, and there is no way to currently test for the genetic

predisposition toward ASD.

Environmental causes:

A child may be exposed to certain environmental factors during the mother’s pregnancy

that may lead to the development of ASD. Some researchers think that ASD is caused

more by environment than by genetics, and that certain people may be born with a

predisposition toward ASD that is only triggered if exposed to certain environmental

stimuli. Some of the suggested environmental stimuli include: a mother who had a viral

or bacterial infection while pregnant; a mother who smoked while pregnant; an older

father; air pollution; and, pesticide exposure.

There is evidence to support some of these environmental factors. For example, women

who were exposed to the rubella infection while they were pregnant have a 7% risk of

giving birth to a child who develops an ASD. Additionally, women who smoked while

pregnant were 40% more likely to have a child who developed an ASD. Also, fathers

over 40 years of age were 6 times more likely to have a child who developed an ASD.

Researchers posit that this may be the case because a father’s genetic material

becomes more vulnerable to mutation as he ages. There is less evidence to support the

idea that air pollution or pesticide exposure causes the development of ASD; however,

studies are currently examining this idea under the CHARGE study [16].

Psychological causes:

A child may have thought processes that contribute to the expression of symptoms of

ASD. A great deal of the research behind the psychological factors that may contribute

to ASD is rooted in a psychological concept called “theory of mind” (TOM) [16]. TOM is

an individual’s ability to understand others’ emotional states; and, at its core involves

seeing the world through the eyes of the other person. The majority of children who do

not have ASD possess a full understanding of TOM by the time they are approximately

4 years of age. Children who have ASD possess a limited or no understanding of TOM.


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This may be one of the causes of the social problems that children with ASD

experience.

Neurological causes:

There are certain problems with how the brain and nervous system develops that may

contribute to ASD symptoms. A great deal of the research into neurological causes has

focused on the amygdala, which is the section of the brain that matches emotions to the

situation the individual is placed in. The amygdala selects emotional responses from the

limbic system and relays them to the cerebral cortex.

Brain studies that have been conducted on people with ASD indicate that the

connections between these systems are not fully functional. The result is that people

with ASD can suddenly experience extreme emotional reactions even to trivial objects

or events. This may explain why people who have ASD favor routines, since routines

and patterns tend not to promote extreme responses. An additional area of research

has been focused on mirror neurons, which enable an individual to mirror another

individual’s actions. For example, a mirror neuron is what allows a baby to smile in

reaction to a mother’s smile. Mirror neurons create more elaborate pathways in the

brain that may contribute to higher brain functions such as language, learning from

others, and the ability to recognize emotional states in others as an individual grows

older. Studies of children with ASD have discovered that mirror neurons in ASD

individuals do not respond in the ways they do those without ASD. Difficulties with

mirror neurons may contribute to the problems that some individuals with ASD

experience with learning and social interaction.

Secondary ASD

Sometimes another medical condition may be the cause of ASD. Some of these

conditions that can cause symptoms of ASD are listed below:

Fragile X syndrome:

This is an uncommon condition that occurs more frequently in boys than it does in girls.

It occurs in about 1 in every 3600 boys, and in about 1 in every 6000 girls [16], and


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presents with certain distinct characteristics such as a long face, larger ears, and

flexible joints.

Tuberous sclerosis:

This is a rare condition that results in multiple tumors to grow throughout the body. The

tumors are not cancerous. This condition occurs in approximately 1 in every 6000

children.

Rett syndrome: This condition, also discussed above, is included here as a rare

secondary ASD and almost always occurs in girls. It causes extreme difficulty with

physical movement, and the individual suffering from Rett syndrome nearly always

requires full assistance with daily tasks. Approximately 1 in every 20,000 girls has Rett

syndrome.

RECENT CHANGES TO THE DSM-V

There have been several refinements made to the diagnostic criteria found in the

Diagnostic and Statistical Manual (DSM), with suggestions based on limitations found in

previous diagnostic criteria [1]. The fourth edition of the DSM (DSM-IV) contained a large

number of diagnoses [17], including a large number of not otherwise specified (NOS)

diagnoses. Additionally, practice has changed in recent years to include the

consideration of the contribution of various comorbidities.

Autism Spectrum Disorders in the DSM-V

ASD in the DSM-V is an umbrella term that will include such disorders as pervasive

developmental disorders, autistic disorder, Asperger syndrome, childhood disintegrative

disorder, and not otherwise specified disorders. ASD’s will consist of these groups of

developmental disorders that are seen on a continuum that ranges from mild to severe

and present in infancy or early childhood. However, in the new DSM-V, the age criteria

for diagnosis will be different; it will not be specified that diagnosis must occur during

childhood and that diagnosis may occur later on in life. Because caregivers might


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compensate for a child’s lack of social intelligence, in school and other social

interactions, a diagnosis of ASD might not be made until later in the child’s life.

Onset of ASD has been extensively studied [2-4], and it is accepted by the majority of

practitioners that diagnosis may occur much later than the time the disorder begins

presenting itself. Additionally, parents and caregivers do not always acknowledge

symptoms immediately as signs of a problem, and the time at which they acknowledge

symptoms is important as well. It is not always easy to detect specific signs and

symptoms of ASD, particularly the early ones [5]. This aspect of ASD is, in particular,

important to the changes in the new DSM-V because onset of symptoms prior to age 3

has been removed. The deletion of the age criteria in the diagnosis of ASD in general

highlights the fact that some individuals are diagnosed later in life, as adolescents or

adults.

It has been suggested that the presence of language delays not be utilized as criteria

for applying a diagnosis of autistic disorder. This is because it has been well established

that a language delay is not a symptom that is specific to ASD. Further, children who

suffer from ASD may develop fluency of speech as they grow even if they suffered from

language delay as a younger child. However, it is important to note that the

development of language is crucial where it regards outcome because a severe

language delay in early childhood seems to predict poor outcome [18].

Considerations regarding specific disorders in the DSM-V are outlined below:

Asperger disorder:

A highly debated change to the revision of the DSM-V is the suggestion to remove

Asperger syndrome. However, the suggestion to remove Asperger syndrome is based

on study evidence that indicates that there is no clear difference between Asperger’s

and autistic disorder where outcome is concerned [1].

Disintegrative disorder:


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While the validity of disintegrative disorder has been debated recently, the debate

focuses on the problems that stem from precisely defining developmental regressions

as well as pinpointing the time of onset of the regression. Additionally, there is the

problem of defining whether developmental delays were present prior to regression.

Further, consideration has been given to whether symptoms or changes present

gradually or suddenly. Due to these ambiguities, the DSM-V therefore suggests removal

of the category of childhood disintegrative disorders.

A goal of this new criterion is to stabilize validity of diagnostic criteria across types of

ASD. Earlier studies have indicated that various types of ASD are not easily

distinguishable from one another [19, 20], which was supported by a recent review [21],

which concluded that criteria for various types of ASD indeed overlap. One study [22]

indicated that this led to differing definitions between such disorders as autistic disorder

and Asperger syndrome between assessment sites, which compromised diagnostic

validity. The conclusion was that distinctions between various types of ASD’s are often

dependent upon the severity of symptoms such as the presence of a learning disability

or language skills. Utilizing an umbrella term such as autistic spectrum disorders helps

place symptoms on a continuum and provides one clear, concise defining term,

therefore preserving diagnostic validity. The major goal of changes to the diagnostic

criteria in the new DSM-V is to make criteria for ASD’s more clear as well as increase

validity of diagnosis.

CHARACTERISTICS OF ASD

Social deficits

Infants and children with ASD are different from typical infants when it comes to social

development [24]. Typically developing infants are very social. They gaze toward faces,

turn toward speaking voices, grasp fingers extended towards them, and smile by the

time they are 2 – 3 months old. Conversely, children who develop ASD have difficulty

with social interactions with other human beings. By 8 – 10 months of age, infants who

go on to develop ASD are generally showing some symptoms such as the failure to


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respond to their names, a reduced interest in other people, and a delay in babbling. By

the time they are toddlers, many of these children have difficulties playing socially with

other children. Additionally, they don’t imitate others and they often prefer to play on

their own instead of with other children. They may not seek comfort from parents or

caregivers as well as show a failure to respond to anger or affection in ways that are

typical.

Research has indicated that children with ASD are attached to caregivers. However, the

way this attachment is expressed is often unusual, and caregivers frequently interpret

the child’s expressions as disconnected or emotionless. It is important to remember that

both children and adults who suffer from ASD have difficulty determining what others

are thinking or feeling. Where children who develop normally learn to accurately

interpret such social cues as smiling, waving or grimacing, these social cues hold little

meaning for the individual who suffers from autism. Individuals with ASD also have

difficulty seeing things from another person’s perspective, meaning that they have little

empathy. While most normally developing five year olds have learned to see things from

another person’s perspective, the person suffering from ASD has not learned this skill,

leading to poor understanding. This may interfere with an ability to predict or understand

actions as well as lead to an inability to understand why another person is feeling the

way they are feeling.

Finally, it is common for individuals who suffer ASD to have difficulty regulating their

emotions. They may come across as emotionally immature, having crying outbursts or

displaying emotions that are inappropriate for the situation. They may also be disruptive

or physically aggressive. These expressions may be particularly pronounced if the

individual with ASD is feeling overwhelmed or frustrated, and can lead to self-injurious

behaviors such as biting or head banging.

Communication difficulties

Infants and children with ASD are different from typical children when it comes to

communication [24]. The majority of children pass predictable milestones to learning


19

language by 3 years of age. The earliest of these is babbling; and, by the age of 1, most

typically developing children will say a few words, acknowledge their names, and point

to or display objects they want. Additionally, children of this age have the ability to

communicate clearly either through sounds or expression when they do not want

something that is given to them. Conversely, children suffering from ASD generally

experience delayed babbling and speaking and may also experience delays in learning

how to utilize gestures to indicate their preferences. Some individuals who develop ASD

may possess these abilities early on and then lose them. Others experience delays and

then gain language ability later on in life.

With therapy, many with ASD do learn how to use spoken language and all with ASD

can learn how to communicate in some way, either verbally or nonverbally. Those who

communicate nonverbally or nearly nonverbally learn to use systems such as pictures,

sign language, word processors, or devices such as speech-generators.

When language does begin to develop, an individual with ASD may utilize speech in

ways that are unusual. For example, some individuals have difficulty forming complete

or meaningful sentences. They may speak single words or phrases or repeat the same

word or phrase over and over again. Others may experience a stage where they repeat

everything they hear word for word, a condition called echolalia. There are others who

have difficulty sustaining conversation despite developing large vocabularies. Still

others carry on long monologues on favorite subjects, giving those listening little

opportunity to respond and having little understanding of the give and take of social

conversation.

Another common communication difficulty is the inability to interpret body language and

tone of voice. For example, sarcasm is particularly difficult for those with ASD to

interpret. An individual who has developed normally may accurately interpret the

sarcasm in a comment such as “Oh, that’s just great!” whereas the individual with ASD

would miss it and interpret the comment as referencing something that actually is just

great. The individual with ASD may also not exhibit typical body language himself or

herself. For instance, their body language may not match what they are saying.


20

Tone of voice may not reflect the emotion and individual with ASD is trying to convey.

Some individuals suffering from ASD utilize flat or robotic sounding voices. These

displays make it difficult for others to understand what individuals with ASD need or

want. This failure in communication can in turn lead to frustration and inappropriate

displays made by the person suffering ASD, such as screaming or grabbing.

Stereotyped or repetitive behaviors and interests

Infants and children with ASD are different from typical children when it comes to

behaviors and interests [24]. Individuals who develop ASD generally engage in repetitive

behaviors as well as have a tendency to engage in a range of activity that is tightly

restricted. Common repetitive behavior includes hand flapping, jumping, rocking,

twirling, arranging or rearranging objects, and the repetition of sounds, words, or

sentences. Occasionally the repetition involves behaviors such as wiggling the hands or

fingers.

Restrictive activities can be clearly seen in the ways children with ASD play with their

toys. Instead of actually playing with their toys, these children will often spend hours

lining the toys up in a specific order. In adults this is seen in the way the individual is

preoccupied with having certain objects lined up in a certain order. Repetitive behavior

may be intensely obsessive and very unusual. It can take any form, including unusual

content or knowledge. This is why some individuals with ASD develop extreme interest

and knowledge of numbers or scientific topics. Individuals with restrictive activities can

become extremely upset if someone or something disrupts the order of their things. This

shows how essential consistency is for many individuals with ASD. Even the slightest

changes in environment or routine can prove very stressful for individuals suffering from

ASD and may lead to outbursts.

Individuals with ASD may have many different obsessions or behaviors, however there

are some that are particularly common among those with ASD. Activities where these

behaviors become notable include: identifying historical dates and events, computers,

certain television programs, trains, and science. Children with ASD in particular like


21

playing with toys such as Thomas the Train and dinosaurs. Older individuals with ASD

may develop repetitive obsessive interests with things like car registration numbers,

traffic lights, shapes, or body parts. Individuals with ASD are also frequently quite

interested in collecting objects; this may be collecting something that seems quite

common, such as a certain toy, or something that seems uncommon, such as leaves.

What marks the behavior as unusual is the duration and intensity that the person with

ASD shows. People with ASD will frequently learn a great deal about the thing they are

obsessed with, be intensely interested in it for an extended period of time, and feel very

strongly about the object or objects in question. There are a number of reasons that

people with ASD develop obsessions, including the fact that obsessions help provide

structure and order, obsessions offer a way to start conversations when social

interactions prove difficult, obsessions help the individual relax or feel happy, and

obsessions offer enjoyment and the opportunity to learn.

Repetitive behaviors can include arm and hand flapping, finger flicking, rocking,

jumping, twirling, spinning, head banging, and more complex body movements.

Repetitive movements also include the repetitive usage of an object, such as the

repetitive flick of a rubber band or repetitively stroking a piece of fabric. Many individuals

with ASD have what is called sensory sensitivity; this means that they are over or under

sensitive to sights, smells, touch, sounds, and tastes. Their balance and body

awareness may also be affected by this sensitivity, and the repetitive behavior is a way

to deal with the sensitivity. There are a number of reasons that people with ASD utilize

repetitive behavior, including attempts to obtain or reduce sensory input, finding ways to

deal with anxiety or stress, or as a way to obtain enjoyment or to occupy one self.

Routines and sameness are also important for the individual with ASD. Routines are

important because they bring order and predictability to the individual’s life and help to

manage anxiety. Repetitive behaviors and obsessions offer routine and order to the

individual who suffers from ASD. However, the need for repetition and routine and order

may extend beyond repetitive behaviors. Some individuals with ASD may have issues

with changes such as those to their physical environment. For instance, if a chair is


22

moved in a room or a new person enters the room, this could be difficult for some

individuals with ASD to handle. Some individuals with ASD may also have very rigid

preferences when it comes to things such as food. For example, they may only eat food

that is a certain color or begins with a certain letter of the alphabet. This may extend to

other areas of life, such as clothing (for example, only wearing clothing made of certain

fabrics) or even to everything objects (for example, only utilizing certain brands of soap

of toilet paper).

Some individuals with ASD may also develop a need to have a routine around daily

activities such as bedtime or meals. These routines may become nearly ritualistic.

Verbal rituals in addition to physically repetitive behaviors may also be seen in the

individual with ASD; and, they may repeat the same question over and over again or

need to hear a specific answer repeatedly. There may also be compulsive behavior in

addition to obsessive behavior that is developed. This means that the individual may do

things like wash their hands or check locks constantly. This behavior is not the same as

having obsessive-compulsive disorder (OCD), although it strongly mirrors it.

Cognitive delays

Children with ASD are different from typical children when it comes to cognitive

development [25]. While cognitive abilities vary, a great many children who have ASD

also have some level of mental retardation. About 75% of people who have ASD have a

non-verbal IQ that is below 70, although ASD may also occur in individuals who are of

normal or high intelligence. There are some children with ASD who also have a high

level of giftedness in a certain area, such as art, music, or math. However, this category

or individuals typically referred to as savants is typically very small and is estimated to

comprise less than 1% of ASD children [25]. If a child with ASD has abilities such as

these they usually manifest by the age of 10.

Children with cognitive delay often present with other delays as well. They also miss

general developmental milestones, particularly the following [26]:


23

Speaking their first words, generally at age 10 – 18 months

Responding to simple instructions, exploring on one’s own, utilizing trial and

error, generally at age 12 months

Walking without aid, generally at age 12 – 18 months

Naming body parts, generally at 18 months

Utilizing phrase speech, generally before the age of 24 – 30 months

Some studies indicate that cognitive delays may be in part the result of drug usage. One

study, the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD), confirmed that

fetal exposure to the drug valproate impairs a child’s IQ well into childhood [25]. This

study was conducted on 310 pregnant women in the United States and the United

Kingdom, with the purpose being to determine if there were differential long-term

neurodevelopmental effects across four frequently utilized drugs: carbamazepine,

phenytoin, lamotrigine, and valproate. Researchers indicate that the use of valproate

during pregnancy led to significant cognitive effects in children, with the child IQ being 8

– 11 points lower (as compared with the other drugs). Valproate was therefore

considered a very poor choice for women who were of childbearing age. While these

results seem to indicate one possible culprit of cognitive delay in those with ASD, further

study is needed to determine how drugs could be contributing to cognitive delays.

A child with ASD may also experience additional mental health conditions or learning

disabilities. For example, they may experience attention difficulties, problems controlling

emotions, or have difficulties learning. There may also be mood or anxiety disorders

present. For example, children with ASD sometimes suffer specific phobias in addition

to ASD. It is also important to note that medication that is utilized to treat symptoms may

affect a child with ASD cognitively. For example, children with ASD who also have

attention deficits do not respond predictably to stimulant medications (i.e.

methylphenidate) that may be prescribed for children with attention deficit disorder.

Keeping in mind that medication may affect the ASD child in unpredictable ways allows

for customization of treatment protocol.


24

ASSOCIATED FEATURES OF ASD

Genetic disorders

One of the biggest advances in understanding the pathophysiology of ASD has been

appreciating the significance of the contribution genetics makes to the etiology of ASD.

There are three main areas of evidence that support this genetic contribution: twin

studies, which compare monozygotic twins (MZ) and dizygotic twins (DZ); family

studies, which compare the rates of ASD in the first-degree relatives versus the general

population; and, studies of genetic syndromes that also co-occur with a diagnosis of

ASD [27]. Each of these will be addressed in turn in the following sections.

Since MZ twins share 100% of genetic material, and DZ twins share 50% of genetic

material (which is similar to siblings who are not twins), and both of these types of twins

share an environment in utero, the higher disease occurrence in MZ twins as opposed

to DZ twins supports the genetic etiology. This has been supported in more than one

twin study and is overall consistent with estimates of heritability at around 70 – 80% [28,

29]. Studies in families indicate that first-degree relatives of those who are autistic have a

marked increased risk of developing ASD as compared to those in the general

population. This is consistent with the strong familial, genetic tie that was observed in

the twin studies [30]. This is not to say that environment does not play a role, but rather

to display that genetics also plays an important role as well. Further, first degree

relatives of those with ASD display an increase in the behavioral and cognitive features

that are associated with ASD, such as language deficits or autistic-like social

impairments [31]; however these often manifest in lesser forms. This is as compared to

the general population [32].

It has also been common knowledge for several decades that there are a number of

medical and genetic conditions that are associated with ASD. For instance, conditions

such as Joubert syndrome, Smith-Lemli-Opitz syndrome, Tuberous Sclerosis, and

Fragile X are all known to cause ASD, although many of these with a lower than 50%

penetrance [33, 34]. Many genes have been identified for ASD; however, few of these


25

genes are specific to ASD but instead contribute to a genetic risk for an associated

disorder that causes ASD.

Epilepsy

Epilepsy is very common in those who suffer from ASD, and increasingly, practitioners

are recognizing it as a problem that must be dealt with in addition to the problems that

come with an ASD diagnosis. Approximately 20 – 30% of those who suffer ASD will

develop epilepsy by the time they become adults [35]. However, actual rates of

comorbidity vary with age and the type of disorder.

Major risk factors for occurrence of a seizure are mental retardation as well as the

presence of additional neurological disorders [36]. Therapeutic approaches to epilepsy in

ASD include conventional treatments; however, should seizures not be evident, there is

controversy as to what treatments should be utilized. Anticonvulsant medication may

interfere with moods or behaviors, and disturbances in moods and behaviors are often

observed in those patients with ASD. There is currently limited understanding regarding

the link between ASD and epilepsy; however, from a clinical standpoint this link should

not be dismissed.

Intellectual disorders

Recent findings [37] indicate that those with ASD also have a high prevalence of

intellectual disorders. Intellectual disabilities are characterized by cognitive, social, and

adaptive deficits, leading to the co-occurrence with other disorders, such as ADHD,

mood disorders, and catatonia and repetitive behaviors, which further complicate

matters. These problems may be problematic not only for the individual suffering from

the disability but also for parents, caregivers, and providers. The disorder may be so

severe as to be debilitating [38].

Matson [39] divides individuals into three distinct groups: those with intellectual disability

(ID), those with ASD, and those with both ASD and ID. Matson states that it is important

for the practitioner to know which type of person he or she is treating, as that will


26

determine the best course of treatment. For instance, an individual with both ID and

ASD will have different needs than the individual who only has ASD.

The combination of intellectual disorders and ASD presents a number of challenges as

well as deficits across a wide range of behaviors or skills that are not seen in those

individuals who have only ID or only ASD. For example, it has been observed [40] that

those individuals with severe autism had more feeding problems that were behaviorally

based, in particular with selecting or refusing food, as compared with those who only

had ID. The combination also increases challenging behaviors. For example, as IQ

goes down, the severity of challenging behaviors in ASD increases. Murphy et al [41]

discovered that self-injury in particular increased. Further, those with ASD tend to not

“grow out” of these types of behaviors; rather, they continue to present significant

challenges over the lifespan, as observed by Murphy et al [41] in a 12-year follow-up

conducted on 141 individuals with severe ASD and ID.

DEVELOPMENTAL COURSE OF ASD

It is commonly believed that those with ASD fall into one of two major developmental

categories [42]. One category involves early onset of impairment and signs and

symptoms of ASD without signs of regression. This is termed gradual onset course. The

other category involves a rather typical development. This typical development is then

followed by loss of language or social skills, sometimes with loss of both, that is paired

with an emergence of ASD-type behaviors such as repetitive or stereotypical behaviors.

This is termed regression course. There is mixed evidence when it comes to prognostic

implications where the regression course is concerned. Some studies indicate that the

regression course is associated with worse outcomes than is the gradual onset course

[43]. Both of these courses may be diagnosed in early to late infancy [44].

There are two approaches that have been taken in order to understand the

development of ASD. These approaches are retrospective and prospective.

Retrospective approaches are mainly based on information gained from reviews of

medical records, parental recall, or observational coding of videotapes made in the


27

home environment during the first or second year of life prior to the ASD diagnosis.

Retrospective studies have generated information that indicates that the core deficits of

ASD are social functioning [45]; however, they also indicate that children who suffer from

ASD also exhibit disruptions in other areas of their lives within the first year of life,

including motor skills, attention, and temperament.

Prospective studies are considered optimal to investigate the timing and nature of how

ASD emerges [42] because prospective, longitudinal studies conducted from infancy

would provide a means of determining patterns of development in those children who

are later diagnosed with ASD. This would later eliminate such confounds as recall bias.

There have been five prospective studies to date that have provided longitudinal data

before the third birthday in children who have ASD as well as in children who are not

affected [46-50]. These studies have all indicated that the development of cognitive,

motor, language, and social skills all appear to be fine at age 6 months. Development

then slows. By the time the children enter pre-school, those with ASD frequently display

motor delays.

Gradual Onset Course

The gradual onset course occurs just as its name suggests; signs and symptoms

present themselves gradually. Parents or caregivers may notice increasing delays in

development or strange behavior, such as an unwillingness to communicate or

communicating in odd ways. One example of this would be a failure to look a person

who is speaking in the face. Other examples include failure to turn when the child’s

name is called or failure to display interests by pointing to objects the child desires.

Stereotypical behaviors may also develop, such as tapping or hand flapping. All of these

behaviors are early warning signs that a child is developmentally delayed and may need

to be screened for ASD.

Regression Course

The regression course occurs when a child is following a pattern of normal

development, generally for the first 12 – 24 months of life, and then he or she appears

to lose skills he or she has acquired. Language regression is considered the most


28

obvious form of regression, but it may also be accompanied by more global regression,

which can involve a loss of social skills or social interest. There is a late-onset

regression course that may occur after the age of 3, but the more common course

occurs prior to the age of 3.

Regression is thought to lead to the more severe course of autism [51], particularly when

young children abruptly lose acquired skills, according to a study published in the

Journal of Autism and Developmental Disorders [52]. There is a particular debate among

scientists as to whether children who regress form a distinct grouping of autistic

individuals, as some studies have indicated that those with regression have poorer

outcomes [53].

The study published in the Journal of Autism and Developmental Disorders surveyed

the parents of 2,720 children and found that those children who regress were more

likely to display more severe symptoms than were those children who had early onset

delays. This was as measured through two standard questionnaires: the Social

Responsiveness Scale and the Social Communication Questionnaire. Children in the

regression group were more likely to receive a diagnosis of autistic disorder as opposed

to a diagnosis that was on the milder end of the spectrum, such as Asperger syndrome,

as compared to their earlier onset peers. Additionally, in a school setting, approximately

70% of children who regress are put into special education settings, with 56% needing a

professional aid.

Communication

Research indicates that regression in communication, particularly in speech and

gestures occurs in approximately 22 – 50% of those children with ASD [54]. The rate is

so variable because the definition for regression is fairly loose and can mean anything

from the loss of a minimum of five words for a period of 3 months to the loss of the

consistent usage of one word used in standard communication. Approximately 30% of

children who experience regression never manage conversational speech.

Social


29

Loss of social skills can mean that the child stops returning the caregiver’s gaze, for

example, or displays a lack of interest in other people when they are in the same space

with him or her. An increased disinterest in social games that the child previously

enjoyed, such as patty cake or peek-a-boo, may become obvious. One meta-analysis

[55] indicates that approximately 38% of children suffer from social regression.

Cognitive

Cognitive decline in ASD manifests as more than a child simply losing what he or she

has learned to date. However, one of the manifestations most clearly seen in cognitive

decline is the loss of language skills. The individual may have been learning language

skills perfectly well and then suddenly loses the ability to learn new skills. Other features

of cognitive decline are the inability to learn new material as well as the development of

associated mental impairments. An example of an associated impairment would be

epilepsy, a common impairment associated with ASD.

Self-help skills

The loss of self-help skills occurs when a child loses the ability to continue to develop

independence. This means that the child fails to develop the ability to feed, clean, and

dress oneself. Children who regress lose the ability to understand how to complete

these tasks and can lack or lose the physical coordination necessary to complete these

tasks. Additionally, the child may lose or not develop an understanding of how or when

to ask for assistance with tasks. These types of tasks help children become socialized

into his or her culture; without them the child is poorly socialized. The fact that many

individuals with ASD are lacking in this area is one reason why they appear to be so

poorly socialized.

EFFECTS OF EARLY INTERVENTION

Early detection of ASD allows for practitioners to intervene in a more timely way with

behavioral therapies that may then improve outcomes. Currently, the American

Academy of Pediatrics guidelines call for the screening of all toddlers at the ages of 18

and 24 months [56]. These are the ages at which the existing screening methods are

most able to identify children at risk for ASD.


30

However, research has shown that a brief questionnaire administered to parents at their

child’s one year well-baby screening may help practitioners identify those children who

have ASD or who are at higher risk for the development of ASD. One study involving

137 pediatricians who administered a 24-item checklist to all caregivers bringing in

children for routine one-year check-ups indicated that about 346 of the 10,500 children

screened were at risk for autism. These children were all referred to an autism clinic to

be evaluated further. Of these children, approximately 50% were followed to age 3; and,

32 of these children received a diagnosis of ASD. Another 56 children were diagnosed

with having a language delay. Of those children diagnosed with delayed language skills,

9 children were diagnosed with having a developmental delay, and; 36 children were

diagnosed with other conditions.

The screening utilized for autism in childhood – called the Communication and Symbolic

Behavior Scales Developmental Profile Infant-Toddler Checklist, took the parents

approximately 5 minutes to complete; and, the screening test predicted autism and

other developmental delays approximately 75% of the time. This indicates that this

questionnaire – or one similar – could be useful in identifying ASD earlier so that more

timely intervention methods may be put to use. Although most pediatricians do not

routinely screen early for ASD and other developmental delays (indeed, prior to the

study, only 30 of the 137 pediatricians participating (22%) had routinely screened for

ASD at 1 year of a child’s life) there seems to be some good evidence that early

intervention efforts do benefit those who suffer from ASD.

The Early Start Denver Model (ESDM), which is a behavioral intervention program

appropriate for children as young as 12 months who are suffering from ASD, has been

found in more than one study to be effective in improving brain response as well as

social skills. ESDM combines applied behavioral analysis (ABA) along with a

developmental relationship based approach to achieve gains in language, cognition,

and everyday living skills. ESDM is a unique approach in part because it works with

children who are very young, but also because it blends ABA with routines that are

based in play and focus on building relationships.


31

One study [57] utilizing ESDM examined 48 children with ASD between 18 and 30

months of age. The children were randomly assigned to either receive ESDM or a

community based intervention regimen for a two-year period. Electroencephalogram

(EEG) activity was measured at the close of the two-year period. The hypothesis was

that children receiving ESDM would show higher levels of brain activity when viewing

faces than when viewing objects than would children who were receiving the typical

community regimen. The children were paired with typically developing children at the

time of their EEG assessment. Additionally a group of typical 4-year-old children was

tested as a comparison group. The children who were receiving the ESDM intervention

regimen were given therapy services for 20 hours per week and parents were also

trained to deliver the intervention regimen. Children who were in the community based

regimen received treatment per usual in their community and were given evaluation,

referrals, as well as resources and reading material at the start of services as well as

two times annually.

On the individual level, the study mentioned above showed that 11 of 15 children in the

ESDM group (73%) and 12 of 17 children (71%) in the control group had higher levels

of brain activity on their EEG assessment when viewing faces as opposed to viewing

objects. This is compared to 5 of 14 (36%) children in the community regimen group. At

the close of the study, the children in the ESDM group exhibited brain activity that was

comparable to typically developing children and that was significantly different from

those children who had received the community regimen. Dr. Geraldine Dawson, a

developer of the ESDM intervention and one of the researchers on the study, stated the

following: “For the first time, parents and practitioners have evidence that early

intervention can result in an improved course of both brain and behavioral development

in young children. It is crucial that all children with autism have access to early

intervention which can promote the most positive long-term outcomes” [57].

Another study [57], also examining the ESDM, found that this same model minimizes the

need for required therapy following the intervention as well as achieves the best

possible outcomes for the individual in terms of IQ, social interactions, and brain activity.


32

The study compared 21 children who received ESDM to 18 children who received a

community intervention regimen during the two years they received their early

intervention regimen as well as the subsequent four years post-intervention. ESDM is

more expensive to deliver in the early years of intervention; there was an average

monthly cost of about $10,000 per child. Children on the community regimen had an

average monthly cost of approximately $5,200. However, the hypothesis was that

despite this greater up-front cost, ESDM would pay off greater dividends on the back

end of things, promoting higher IQ, greater ease in social interactions, increased brain

activity, and reduced therapy, leading to an overall reduced cost.

In the four years following the early intervention, the children who had received the

ESDM required an average of approximately $4,450 in related services such as speech,

physical, and occupational therapy, as well as ABA. The children who received the

community regimen required an average of approximately $5,550 in related speech,

physical, and occupational therapy, as well as ABA. Study researchers believe this is

very telling and differences in cost may be even broader than study results suggest, as

the defining factors for related expenses were kept fairly narrow. David S. Mandell,

study researcher expressed the following: “I believe the cost efficiencies would become

even more pronounced if there had been an evaluation on health costs and overall

family economics such as the ability of both parents to continue to work and earn

income while their child received services” [57].

These two studies offer powerful evidence for the idea that early intervention such as

early screening as well as methods such as ESDM may prove to offer better outcomes

for those individuals who suffer from ASD, and in turn offer parents and caregivers a

better outcome as well. Early intervention may help a child in the form of increased

cognitive and social skills, and a family in terms of long-term financial savings.

Therefore, there is strong evidence to suggest that early intervention benefits everyone

involved with ASD.

RISK FACTORS


33

There are a number of risk factors that contribute to ASD. There are both heritable and

non-heritable risk factors. These risk factors are discussed below.

Gender

While ASDs occur in all racial, ethnic, socioeconomic, and gender groupings, it is well

known that males have a greater likelihood than do females of developing an ASD. The

ratio is as high as 5:1 [58]. It is not known or well understood why there is this

discrepancy. It is also not known if concrete differences in development or presentation

occur between genders. Males with ASD do have certain advantages over females with

ASD. Research indicates that females with ASD tend to have lower Intelligence

Quotients (IQ) than do males [59]. Males also show stronger verbal, motor, and social

skills. However, when controlling for language, females display stronger nonverbal

problem solving abilities.

A recent study published in JAMA Pediatrics [60] that examined the records of more than

625,000 births indicated that birth that involved both augmented and induced labor was

linked to a 35% higher instance of ASD as compared with labor that did not receive

either treatment. The study further indicates that augmented or induced labor was linked

with a smaller increased risk in boys. In girls, only the augmented birth was linked with a

small increased risk. The researchers did control for a number of associated factors that

have been shown to increase the risk of autism, such as the health or age of the

mother. Researchers in the study added that the study results did not necessarily

indicate cause and effect; rather, there could be other factors at play that have as yet

been unidentified. One of these factors may be the usage of Pitocin (oxytocin) that is

utilized to induce or augment labor. Approximately 50 – 70% of women who undergo

induction in the United States receive Pitocin injections. There are other contributors

that may be a factor, such as pregnancy conditions or delivery events that lead up to the

need to induce labor. Further study is needed to determine why augmented and

induced labor is leading to this increased the risk of ASD in boys.

Genetics


34

Twin studies provide evidence to support that there is a heritable component to ASD

etiology, although there has not been any particular gene discovered that predisposes

an individual to ASD [61]. Twin studies have been done on both monozygotic (identical)

and dizygotic (fraternal) twins. Monozygotic twins share all of their genes, whereas

dizygotic twins share half of their genes, on the average. Studies have indicated that

there are increased disease concordance rates among monozygotic twins as compared

to dizygotic twins. A recent study indicated that there is a 60% monozygotic

concordance among 25 sets of twins as compared to a 0% dizygotic concordance

among 20 sets of twins [62]. This data suggests that there is a high rate of heritability.

However, the suggestion has been made that estimations from twin studies may be

overstated. Still, the large heritability discovered in twin studies is supported through

familial aggregation studies [63].

Several studies have also shown a heightened risk for ASD amongst siblings of cases.

This is termed “sibling relative risk” [61] and is estimated as the “ratio of the risk for ASD

among siblings of cases to the risk, or prevalence, in the general population” [61]. The

probability that a sibling of a case will develop ASD is estimated at between 2 % and

6% [64, 65], although there are some estimates that are as high as 7% for siblings of male

cases and 14% of siblings for female cases [66]. It is important to remember, however,

that these numbers are entirely dependent on the population prevalence estimates at

the time of sampling, leading to higher or lower estimations, depending on what is

happening in the population.

There is also another avenue of support for genetic association, and this is the overlap

of ASD with certain genetic disorders such as tuberous sclerosis [67], neurofibromatosis

[68], and Fragile X syndrome [69, 70]. To that end, abnormalities on nearly every

chromosome have been associated with one form or another of ASD phenotype, most

notably on chromosomes 7, 15, and X [71]. The most frequently cited of these are

duplications and deletions of the proximal area of chromosome 15 [72-75]. Breakpoints for

chromosomal inversions that result in features of ASD frequently lie in fragile regions of

chromosomes, which lead to speculations about the possible role of unstable regions of

DNA and submicroscopic chromosomal deletions [76, 77].


35

Prenatal and Perinatal Factors

There are specific prenatal factors that may contribute to development of ASD. One

such factor is maternal infections. In several studies [61], maternal infections were

measured with non-specific indicators, which included maternal recall of symptoms such

as fever as well as information archived in medical records. While the studies did not

attain statistical significance for the infection measure, each reported a ratio of odds that

were above 1.0 [78-80].

There are specific infections that are known to affect developing brains; of these that

have been most commonly known to affect the developing brain as well as to be

commonly associated with ASD is rubella. However, it has also been shown that other

infections, such as herpes, syphilis, and varicella, as well as the flu, also have a higher

than normal association with ASD. Another factor is prenatal and intrapartum

pharmaceutical usage. For example, utilizing thalidomide during days 20-24 of gestation

has been associated with increased risk of ASD [81, 82]. This suggests that xenobiotics

may play a role in the etiology of ASD. Animal studies [83, 84] and case studies [85, 86]

reflect findings that valproic acid as well as other anticonvulsants may increase ASD

risk. This is an interesting association, as these same drugs may prove therapeutic for

non-epileptic children who suffer from ASD [87-89].

There are also some preconception factors that may be associated with development of

ASD. For instance, in the 1970s the idea that environmental exposure to certain

chemicals arose [90]. This hypothesis was revisited in the 1990s when parents without

incidence of ASD who lived close to plastic manufacturing plants appeared to have a

higher incidence of children with ASD [91]. However, upon examination, the

Massachusetts Department of Public Health concluded that further investigation of the

cases in question was not needed [92].

While preconception chemical exposure factors have not been thoroughly explored,

hypotheses of postnatal chemical exposures have been more thoroughly investigated,

primarily through looking at case studies. However, epidemiologic evidence for specific


36

postnatal environmental exposure that in turn leads to development of ASD is not

substantial. One of the more comprehensive investigations into the matter was

conducted in Brick Township, New Jersey, where there was a high local presence of

ASD near local landfills. This raised concerns that landfills were leaching chemicals into

the drinking water or into local swimming areas. The Agency for Toxic Substances and

Disease Registry looked into the possible exposure pathways, as well as evaluated data

on levels of trihalomethanes, tetrachloroethylene, and thrichloroethylene. While these

chemicals were present in the drinking water at various times during the study, the

levels were found to be low or in locations that did not correspond with the locations

being studied or with the timing of the pregnancies being studied [93, 94].

Neuroanatomical Abnormalities

Neuroanatomical abnormalities in the brains of individuals with ASD provide concrete

evidence that there is a neurobiological component to ASD [95], that the disease is more

than just a behavioral disorder with purely environmental contributions.

The neurobiology of the disorder has been examined since the dawn of the disorder,

and both genetic and non-genetic factors have been shown [96]. However, particular

etiologic factors are as yet undefined. Frontal lobe volume does appear to be decreased

in individuals with autism [97]; there also appears to be a decrease in gray matter (GM)

volume in the orbitofrontal cortex [98] as well as an abnormally thin frontotemporal cortex

[99]. However, conflicting studies [100-102] have reported that GM volume and thickness is

actually enlarged in these areas.

An increase in GM volume has also been indicated in areas involved in communicative

and social functions, to include the dorsal and medial prefrontal regions, the lateral and

medial temporal area, the parietal regions, and the auditory and visual association

cortices [103-106]. Likewise, discrepant white matter (WM) have been indicated in autism,

including regional increases [107-109], as have decreases in cross-sectional areas and the

microstructure of the corpus callosum [110, 111]. Concomitant WM disruptions have been

indicated in prefrontal, superior temporal, temporoparietal cortices and the corpus

callosum, but there have also been observations of an increase in whole brain WM [101,

109]. It is not clear how these anatomic abnormalities related to domain specific cognitive


37

impairment in social functioning, emotional functioning, language deficits,

communication deficits, and deficient executive function.

Microscopic observations of the brains of individuals with ASD have discovered reduced

cell size as well as increased cell-packing density (meaning an increased number of

nerve cells per unit volume) in the hippocampus, amygdala, mammillary body, anterior

cingulate gyrus, and medial septal nucleus [112]. These structures are recognized as

being connected to one another by interrelated circuits. They also comprise a major

portion of the limbic system. The limbic system is acknowledged to be important to

emotion and behavior, as well as learning and memory. It also plays a large role in the

integration, processing, and generalization of information. Abnormalities of the limbic

system may account for a lot of the major clinical features of ASD, including language

dysfunction as well as social deficits.

Additionally, abnormalities have been located in the cerebellum, where the amount of

Purkinje cells is much reduced, particularly in the posterior and inferior parts of the

hemispheres bilaterally. The vermis microscopically appears normal.

Abnormalities have also been seen in the deep cerebellar nuclei. These findings appear

to vary along with the age of the patient. Comparable observations have been seen in

the inferior olivary nucleus neurons as well as the neurons of the nucleus of the

Diagonal Band of Broca. The fact the the olivary neurons are preserved even in the face

of such markedly reduced number of Purkinje cells indicates that these brain lesions are

likely of prenatal origin.

The role of the cerebellum in ASD is not certain. Some studies [112] show that it may play

a role in the modulation of language, attention, emotional affect, mental imagery,

cognition, and anticipatory planning. Therefore, it is likely that the abnormalities in both

the limbic system and the cerebellum are important to understanding the clinical

features of ASD.

Brain enlargement

Brain changes prior to the age of 2 may lead to brain enlargement that in turn leads to

ASD. One study conducted by University of North Carolina (UNC) researchers found


38

that children with ASD who had enlarged brains at the age of 2 years also had enlarged

brains at the ages of 4 and 5. However, their brain growth was not markedly different

than it had been at 2 years old.

Researchers conducted their original study in 2005, with a follow-up study conducted in

2011. In 2005, researchers discovered that 2-year-old participants with ASD had brains

that were up to 10% larger than those of children at the same age that did not have

ASD. The follow-up study indicated that the children with ASD continued to have brain

enlargement in subsequent years, but at the same level they had it at 2 years old. This

finding led researchers to conclude that the changes they detected at the age of 2 were

due to growth prior to that time period. Additionally, the study discovered that the

enlargement was affiliated with an increase in folding on the surface of the brain, not an

increase in gray matter. Researchers posit that this increase is more than likely genetic

and results from “an increase in the proliferation of neurons in the developing brain” [114].

The researchers suggest that the brain overgrowth may be occurring around the child’s

first birthday.

Another study conducted by the University of California Davis MIND Institute indicated

that those children who were later diagnosed with ASD were found to have an excess of

cerebrospinal fluid as well as enlarged brains in infancy. This brought up the possibility

that these types of brain abnormalities may serve “as potential biomarkers for the early

identification of the neurodevelopmental disorder” [115]. The study is the first to link the

excess of cerebrospinal fluid that existed during infancy to the development of ASD. A

potential positive outcome to the study is that it would offer practitioners a new way to

positively screen for ASD, because the brain anomaly would be detectable utilizing a

conventional MRI. Therefore, early detection would be possible; this is crucial in

children who have ASD because it allows for timely intervention.

Early intervention offers the most hope in decreasing the behavioral and cognitive

impairments associated with ASD and increasing positive long-term outcomes. This

study was conducted on 55 children who were between 6 – 26 months of age. Thirty-

three of these children had an older sibling who had an ASD. Twenty-two were children


39

who had no family history of ASD. Researchers indicated that the brain anomaly was

more significantly detected in those infants who were high risk and who were later

diagnosed with ASD between 24 and 26 months of age.

Another study [116] examined abnormal brain growth and onset status: early onset or

regressive onset. This particular study examined 2 – 4 year olds whose status was

either non-regressive (n = 53) or regressive (n = 61). There was also a control group of

non-affected 2 – 4 year olds (n = 66). Researchers discovered that abnormal brain

enlargement was most commonly discovered in boys with regressive ASD. Brain size in

boys who were non-regressive did was not different from the control group.

Retrospective head circumference measurements were also taken, and it was

discovered that head circumference in boys with regressive ASD is normal at birth but

then diverges at around 4 – 6 months of age. Girls who have autism do not have any

difference in brain size from those in the control group. Researchers posit that these

results indicate that there could be certain neural phenotypes that are associated with

the different types of onset of ASD. For instance, the rapid head growth may be a risk

factor for regressive type ASD.

Environmental Factors

There are several environmental factors that may be associated with the development

of ASD. One of these is childhood infection. There have been reports of sudden onset

of ASD symptoms in older children following herpes encephalitis [117-119]. There are other

infections that can result in secondary hydrocephalus; for example, meningitis. These

infections may lead to development of ASD [120]. One study indicated that mumps,

chicken pox, fever of unknown origin, and ear infections were significantly associated

with an increased risk of development of ASD [121].

Some vaccinations may also increase the risk for development of ASD. A paper

published in 1998 indicated that the measles-mumps-rubella vaccine might be linked to

ASD development [122]. However, epidemiologic studies have not provided evidence that

supports a link between the vaccine and the risk of developing ASD [123-127]. Similarly,


40

case study comparisons do not find any indication of post-vaccination increase in risk of

developing ASD [123, 128]. Further, a population based retrospective study that included

more than half a million children from Denmark who were born between 1991 and 1998,

82% who had received the measles-mumps-rubella vaccine, discovered no association

between the vaccine and development of ASD [129].

There are additional concerns over vaccines and ASD, which stem from the usage of

thimerosal, which is a preservative that contains ethylmercury. Ethylmercury is itself

similar to methylmercury, which is a known fetal neurotoxin that can cause severe brain

injury at high doses and leads to developmental delays and dysfunction at lower doses

[130]. There is limited data that suggests that higher doses of ethylmercury is similar to

higher doses of methylmercury [131, 132], and there is no data on low dose exposure to

ethylmercury. There is not much data on the association to date.

Data from the Vaccine Safety Datalink of the Centers for Disease Control and

Prevention indicates weak association between thimerosol related exposure to mercury

and related neurodevelopmental disorders, but not association to ASD itself [133].

Existing evidence is considered to be inconclusive. Although Thimerosal has been

removed from vaccines, there are still many individuals alive with ASD who have

received vaccinations that contained thimerosal.

Other environmental factors include birth complications, including umbilical cord

complications, fetal distress, injury or trauma during birth, multiple births, maternal

hemorrhage, summer births, low birth weights, congenital malformations, low 5-minute

Apgar score, feeding difficulty, neonatal anemia, meconium aspiration,

hyperbilirubenemia, and ABO or Rh incompatibility [134]. Parental age at the time of

conception is also a factor; and, this includes the age of both parents. One study [135]

indicated that firstborn children of 2 parents who were older were 3 times more likely to

develop ASD than were third or later born children of mothers who were 20 – 34 years

of age and fathers who were <40 years of age. Therefore, the risk of ASD increases

with both maternal and paternal age.


41

Another environmental risk factor may be waiting less than a year between

pregnancies. One study [136] indicated that pregnancies that are closely spaced are

associated with an increase in ASD. The study examined pairs of first and second born

siblings in California that occurred between 1992 and 2002 and examined ASD

diagnoses in these siblings. Results of the study indicated that children who were born

after shorter intervals between the pregnancies were at an increased risk of developing

an ASD, with the highest risk being associated with pregnancies that were spaced less

than a year apart.

One more environmental risk factor may be not taking prenatal vitamins, as taking

prenatal vitamins has been shown to slightly reduce the odds that a child will develop

ASD. One study examining Northern California families enrolled in the Childhood

Autism Risks from Genetics and Environment (CHARGE) study [137] concluded that

mothers who had children with ASD were less likely than were mothers of non-affected

children to have taken a prenatal vitamin during the 3 months prior to pregnancy or in

the first month of pregnancy. This led researchers to conclude that the peri-conceptional

use of prenatal vitamins may reduce risk of birthing a child with ASD, particularly in

those who are already genetically susceptible to ASD.

What is important to note regarding environmental risk factors is they do not affect a

child in a vacuum. Many children are exposed to environmental risk factors without

developing ASD. This leads researchers to conclude that if a child is genetically

predisposed to ASD, for example, then these types of environmental risk factors may

increase the risk of development of an ASD. Studies have indicated that there are other

environmental factors - such as the maternal use of antipsychotics and mood

stabilizers – that may increase the risk of development of ASD. However, the risk must

also be weighed against the mother’s need, which can also affect the health of the child

she will be having. Additionally, most risk factors that are not yet well documented may

only increase the risk of development of ASD slightly as compared with other risk

factors, such as genetic predisposition, making it difficult to pinpoint how, exactly,

environmental factors contribute to the larger overall picture of each single ASD

diagnosis.


42

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