Autism

Autism
ICD-10	ICD10 F84.0-F84.1
ICD-9	299.0
OMIM	209850
MedlinePlus	001526

Autism (pronounced aw'tizm) is classified by the World Health Organization and American Psychological Association as a developmental disability that results from a disorder of the human central nervous system. It is diagnosed using specific criteria for impairments to social interaction, communication, interests, imagination and activities.

Autism manifests itself "before the age of three years" according to the World Health Organization's International Classification of Diseases (ICD-10) Autistic children are marked by delays in their "social interaction, language as used in social communication, or symbolic or imaginative play" (Diagnostic and Statistical Manual of Mental Disorders).

Autism, and the other four pervasive developmental disorders (PDD), are all considered to be neurodevelopmental disorders. They are diagnosed on the basis of a triad, or group of three behavioral impairments or dysfunctions: 1. impaired social interaction, 2. impaired communication and 3. restricted and repetitive interests and activities.

From a physiological standpoint, autism is often less than obvious in that outward appearance may not indicate a disorder. Diagnosis typically comes from a complete patient history and physical and neurological evaluation.

The incidence of diagnosed autism has increased since the 1990s. Reasons offered for this phenomenon include better diagnosis, wider public awareness of the condition, regional variations in diagnostic criteria, or simply an increase in the occurrence of ASD (autism spectrum disorders). The United States Centers for Disease Control and Prevention (CDC) estimate the prevalence of autism spectrum disorders to be about one in every 150 children. In 2005, the National Institute of Mental Health (NIMH) stated the "best conservative estimate" as 1 in 1000. In 2006, NIMH estimated that the incidence was 2-6 in every 1000

There are numerous theories as to the specific causes of autism, but they are as yet unproven (see section on "Causes" below). Proposed factors include genetic influence, anatomical variations (e.g. head circumference), abnormal blood vessel function and oxidative stress. Their significance as well as implications for treatment remain speculative.

History

The word autism was first used in the English language by Swiss psychiatrist Eugene Bleuler in a 1912 issue of the American Journal of Insanity. It comes from the Greek word for "self," αυτος (autos). Autism was actually confused with schizophrenia during the early stages of observation. Bleuler used the term to describe the schizophrenics' seeming difficulty in connecting with other people.

However, the medical classification of autism as a separate disorder or disease did not occur until 1943 when psychiatrist Dr. Leo Kanner of the Johns Hopkins Hospital in Baltimore, Maryland reported on 11 child patients with striking behavioral similarities and introduced the label "early infantile autism." He suggested the term "autism" to describe the fact that the children seemed to lack interest in other people, emphasizing "autistic aloneness" and "insistence on sameness". Kanner's first paper on the subject was published in the journal The Nervous Child (no longer in publication), and almost every characteristic he originally described is still regarded as typical of the autistic spectrum of disorders diagnostic triad of behavioral impairments or dysfunctions: 1. impaired social interaction, 2. impaired communication and 3. restricted and repetitive interests and activities..

Leo Kanner's contemporary in Austria, Dr. Hans Asperger, made similar observations, although his name has since become attached to a different form of autism known as Asperger's Syndrome. Widespread recognition of Asperger's work was delayed by World War II in Germany. His seminal paper was not actually translated into English for almost 50 years and the majority of his work was not widely read until 1997.

Autism and Asperger's Syndrome are today listed in the DSM-IV-TR as two of the five pervasive developmental disorders (PDD), which also include Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise Specified (or atypical autism). Health care providers also refer to autism spectrum disorders (ASD) which includes only three of those listed in PDD: Autistic disorder, Asperger syndrome, Pervasive Developmental Disorder Not Otherwise Specified. All of these conditions are characterized by varying degrees of deficiencies in communication skil]s and social interactions, along with restricted, repetitive, and stereotyped patterns of human behavior.

Characteristics

On the surface, individuals who have autism are physically indistinguishable from those without. Some studies show that autistic children tend to have larger head circumferences but the significance in the disorder is unclear. Sometimes autism co-occurs with other disorders, and in those cases outward differences may be apparent.

Individuals diagnosed with autism can vary greatly in skills and behaviors, and their response to sensory input shows marked differences in a number of ways from that of other people. Certain stimulations, such as sounds, lights, and touch, will often affect someone with autism differently than someone without, and the degree to which the sensory system is affected can vary greatly from one individual to another.

Key behaviors

Autistic children may display unusual behaviors or fail to display expected behaviors. Normal behaviors may develop at the appropriate age and then disappear or, conversely, are delayed and develop quite some time after normal occurrence. In assessing developmental delays, different physicians may not always arrive at the same conclusions. Much of this difference between diagnosis is due to the disputed criteria for autism. Disagreement on deciding how a child should normally behave also makes it difficult to construct objective test of child behavior.

Essentially, the diagnosis of autism must meet specific criterion but there are also many characteristics that are idiosyncratic. Thus, autism is not a "one size fits all" label. As a result, the spectrum disorder encompasses a very wide range of behaviors and symptoms.

Some behaviors cited by the National Institute of Child Health and Human Development (listed below) may simply mean a normal delay in one or more areas of development, while others are more typical of ASDs—Autistic Spectrum Disorders.

The list below is not all-inclusive, and generally applies to children and not adults. Furthermore, while some of these behaviors might be seen in a person with autism, others may be absent.

Noted behaviours

• does not respond to his/her name.
• cannot explain what he/she wants.
• language skills are slow to develop or speech is delayed.
• doesn't follow directions.
• will fuss if didn't get what wanted.
• at times, the child seems to be deaf.
• seems to hear sometimes, but not other times.
• doesn't point or wave "bye-bye."
• doesn't understand the concept of pointing; will look at the hand pointing rather than the object being pointed at.
• used to say a few words or babble, but now he/she doesn't.
• throws intense or violent tantrums.
• has odd movement patterns.
• likes to spin around in a circle.
• likes being in a place well known.
• hands on ears oftenly.
• is overly active, uncooperative, or resistant.
• doesn't know how to play with toys.
• doesn't smile when smiled at.
• has poor eye contact.
• gets "stuck" doing the same things over and over and can't move on to other things.
• seems to prefer to play alone.
• gets things for him/herself only.
• is very independent for his/her age.
• does things "early" compared to other children.
• seems to be in his/her "own world."
• seems to tune people out.
• is not interested in other children.
• dislikes playing pretend.
• walks on his/her toes.
• shows unusual attachments to toys, objects, or schedules (i.e., always holding a string or having to put socks on before pants).
• spends a lot of time stacking objects, lining things up or putting things in a certain order.
• unconcerned about - or completely oblivious to - dangers around him/her (i.e., standing in the middle of the street without worrying about getting hit by a car).

Autism and blindness

The characteristics of a person with both an Autism Spectrum Disorder (ASD) and a severe visual impairment (VI) may vary from a person with just ASD or just VI. Historically, many behaviors of blind children were seen as "autistic-like" but were attributed to their blindness rather than pursuing possibilities of autism.

Developmental trajectories of children with ASD-VI are often very similar as those followed by children with typical autism, but the child with ASD-VI will have particularly unusual responses to sensory information. The person may be overly sensitive to touch or sound, or be less responsive to pain. Typically, touch, smell, and sound are affected the most dramatically.

Repetitive behaviors

Although people with autism usually appear physically normal, unusual repetitive motions, known as self-stimulation or "stimming," may set them apart. These behaviors might be extreme or subtle. Some children and older individuals spend a lot of time repeatedly flapping their arms or wiggling their toes, others suddenly freeze in position. Some spend hours arranging objects in a certain way rather than engaging in pretend play as a typical child might, and becoming agitated if they are re-arranged or moved. Repetitive behaviors can also extend into the spoken word; perseveration of a single word or phrase can also become a part of the child's daily routine. Some may repeat words from movies and watch certain bits over and over again. Autistic children may demand consistency in their environment. A slight change in the timing, format or route of a routine or trip can be extremely disturbing to them. Autistics sometimes have persistent, intense preoccupations. For example, the child might be obsessed with learning all about computers, television programs, lighthouses or virtually any other topic.

DSM definition

Autism is defined in section 299.00 of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as:

1. A total of six (or more) items from (1), (2) and (3), with at least two from (1), and one each from (2) and (3):
   1. qualitative impairment in social interaction, as manifested by at least two of the following:
      1. marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction
      2. failure to develop peer relationships appropriate to developmental level
      3. a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)
      4. lack of social or emotional reciprocity
   2. qualitative impairments in communication as manifested by at least one of the following:
      1. delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)
      2. in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others
      3. stereotyped and repetitive use of language or idiosyncratic language
      4. lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level
   3. restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:
      1. encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus
      2. apparently inflexible adherence to specific, nonfunctional routines or rituals
      3. stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)
      4. persistent preoccupation with parts of objects
2. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years:
   1. social interaction
   2. language as used in social communication
   3. symbolic or imaginative play.
3. The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder.

Types of autism

Autism presents in a wide degree, from those who are nearly dysfunctional and apparently mentally disabled to those whose symptoms are mild or remedied enough to appear unexceptional ("normal") to others. Although not used or accepted by professionals or within the literature, autistic individuals are often divided into those with an IQ<80 referred to as having "low-functioning autism" (LFA), while those with IQ>80 are referred to as having "high-functioning autism" (HFA). Low and high functioning are more generally applied to how well an individual can accomplish activities of daily living, rather than to IQ. The terms low and high functioning are controversial and not all autistics accept these labels. Additionally, a recent review questioned the validity of IQ testing of autistic people.

This discrepancy can lead to confusion among service providers who equate IQ with functioning and may refuse to serve high-IQ autistic people who are severely compromised in their ability to perform daily living tasks, or may fail to recognize the intellectual potential of many autistic people who are considered LFA. For example, some professionals refuse to recognize autistics who can speak or write as being autistic at all, because they still think of autism as a communication disorder so severe that no speech or writing is possible.

As a consequence, many "high-functioning" autistic persons, and autistic people with a relatively high IQ, are under diagnosed, thus making the claim that "autism implies retardation" self-fulfilling. The number of people diagnosed with LFA is not rising quite as sharply as HFA, indicating that at least part of the explanation for the apparent rise is probably better diagnostics. Many also think that ASD's are being over diagnosed: (1) because the growth in the number and complexity of symptoms associated with autism has increased the chances professionals will erroneously diagnose autism and (2) because the growth in services and therapies for autism has increased the number who falsely qualify for those often free services and therapies.

Asperger's Syndrome and Classic Autism Disorder

In the current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), the most significant difference between Autistic Disorder and Asperger's syndrome is that a diagnosis of the former includes the observation of "delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play", while a diagnosis of Asperger's syndrome observes "no clinically significant delay" in the latter two of these areas.

While the DSM-IV does not include level of intellectual functioning in the diagnosis, the fact that those with Asperger's syndrome tend to perform better than those with classic autism has produced a popular conception that Asperger's syndrome is synonymous with "higher-functioning autism", or that it is a lesser disorder than autism.

The extent to which someone with higher functioning autism or Asperger's syndrome may excel is theoretically quite high. For example, Henry Cavendish, one of history's foremost scientists, may have been autistic. George Wilson, a notable chemist and physician, wrote a book about Cavendish entitled, "The Life of the Honourable Henry Cavendish", published in 1851. From Wilson's detailed description it seems that while Cavendish may have exhibited many classic signs of autism, he nevertheless had an extraordinary mind.

Autism as a spectrum disorder

Another view of these disorders is that they are on a continuum known as autistic spectrum disorders. Autism spectrum disorder is an increasingly popular term that refers to a broad definition of autism including the classic form of the disorder as well as closely related conditions such as PDD-NOS and Asperger's syndrome. Although the classic form of autism can be easily distinguished from other forms of autism spectrum disorder, the terms are often used interchangeably.

A related continuum, Sensory Integration Dysfunction, involves how well humans integrate the information they receive from their senses. Autism, Asperger's syndrome, and Sensory Integration Dysfunction are all closely related and overlap.

Some people believe that there might be two manifestations of classical autism, regressive autism and early infantile autism. Early infantile autism is present at birth while regressive autism begins before the age of 3 and often around 18 months. Although this causes some controversy over when the neurological differences involved in autism truly begin, some speculate that an environmental influence or toxin triggers the disorder. This triggering could occur during gestation due to a toxin that enters the mother's body and is transferred to the fetus. The triggering could also occur after birth during the crucial early nervous system development of the child.

A paper published in 2006 concerning the behavioral, cognitive, and genetic bases of autism argues that autism should perhaps not be seen as a single disorder, but rather as a set of distinct symptoms (social difficulties, communicative difficulties and repetitive behaviors) that have their own distinct causes. An implication of this would be that a search for a "cure" for autism is unlikely to succeed if it is not examined as separate, albeit overlapping and commonly co-occurring, disorders.

Epidemiology

Gender differences

The ratio of incidence between males and females (as demonstrated in the scientific literature) is ambiguous. Studies have found much higher prevalence in males at the high-functioning end of the spectrum, while the ratios appear to be closer to 1:1 at the low-functioning end. In addition, a study published in 2006 suggested that males over 40 are more likely than younger males to parent a child with autism, and that the ratio of autism incidence in males and females is closer to 1:1 with older fathers.

Reported increase with time

There was a worldwide increase in reported cases of autism over the decade to 2006. There are several theories about the apparent sudden increase.

Many epidemiologists argue that the rise in the incidence of autism in the United States is largely attributable to a broadening of the diagnostic concept, reclassifications, public awareness, and the incentive to receive federally mandated services. However, some authors indicate that the existence of an as yet unidentified contributing environmental risk factor cannot be ruled out. On the other hand, a widely-cited pilot study conducted in California by the UC Davis M.I.N.D. Institute (17 October, 2002), reported that the increase in autism in California is real, even after accounting for changes to diagnostic criteria.

The question of whether the rise in incidence is real or an artifact of improved diagnosis and a broader concept of autism remains controversial. Dr. Chris Johnson, a professor of pediatrics at the University of Texas Health Sciences Center at[San Antonio and co-chair of the American Academy of Pediatrics Autism Expert Panel, sums up the state of the issue by saying, "There is a chance we're seeing a true rise, but right now I do not think anybody can answer that question for sure."

Treatment

The efficacy of treating Autism is disputed. There is a broad array of proposed autism therapies with various goals, e.g. improving health and well-being, emotional problems, difficulties with communication and learning, and sensory problems for people with autism but the effectiveness of these appraoches is not clear.

Physiology and neurology

Autism appears to involve a greater amount of the brain than previously thought. A study of 112 children (56 with autism and 56 without), published in the Journal of Child Neuropsychology, found those with autism to have more problems with complex tasks, such as tying their shoelaces or writing, which suggests that many areas of the brain are involved. Children with autism performed simple tasks as well as or better than those without. In tests of visual and spatial skills, autistic children did well at finding small objects in complex pictures (e.g., finding the character Waldo in "Where's Waldo" pictures). However, they found it difficult to tell the difference between similar-looking people. Children with autism tended to do well in spelling and grammar, but found it much more difficult to understand complex speech, such as idioms or similes when the meaning of the phrase is figurative. They would, for example, not understand that "He kicked the bucket" meant someone had died, or were likely to actually hop if told to "hop to it".

The research from this perspective has a number of implications:

• Autism is more than likely a global disorder which affects how the brain processes the information it receives, while complex information tends to make this more readily apparent.
• Neurological ‘wiring’ in people with autism manifest abnormalities in the areas of the brain that communicate with each other.
• Observed abnormalities provide a reasonable explanation for why children with autism have problems with complex tasks which require multiple areas of the brain to work together; autistic people tend to do better in tasks that only require one region of the brain.
• The causes of autism are possibly more pervasive than previously believed; for example, more areas of the brain are affected than just those involving social interaction, communication, interests, and imagination.
• Autism may not be primarily a disorder of social interaction; research must now take into account non-social aspects.

A possible explanation for the characteristics of the syndrome is a variation in the way the brain itself reacts to sensory input and how parts of the brain then handle the information. An electroencephalographic (EEG) study of 36 adults (half of whom had autism) at Washington University in St. Louis found that adults with autism show differences in the manner in which neural activity is coordinated. The implication seems to be that there is poor internal communication between different areas of the brain. (Electroencephalographs, or EEGs, measure the activity of brain cells.)

The Wash. U. study indicated that there were abnormal patterns in the way the brain cells were connected in the temporal lobe of the brain. (The temporal lobe deals with language.) These abnormal patterns would seem to indicate inefficient and inconsistent communication inside the brain of autistic people.

Studies in neuropathology indicate abnormalities in the amygdala, hippocampus, septum, mamillary bodies, limbic system,and the cerebellum.

• Autistic brains are slightly larger and heavier and a larger than normal head circumference is commonly noted.
• In the limbic system, there is an excess of cells and they are too small. The neurons themselves appear to be underdeveloped. Dendritic trees which provide the basis for connections between neurons are truncated (i.e. shortened).
• In the cerebellum, purkinje cells are widely affected. The anatomic differences correlate to the curtailment of development earlier than 30 weeks gestation. In other words, the development of the cells appears to have stopped at some time before the 30th week in utero
• An enlarged third ventricle of the brain appears to accompany autism in those who are non-mentally retarded, but the reasons for this and its effects are still unknown.

Research has not yet established exactly what is specific to autism and what may be seen in other disorders however.

Individuals with autism are also far more likely to develop epilepsy than would otherwise be expected (estimated 10-30% incidence).

Mirror neurons

A theory featuring mirror neurons states that autism may involve a dysfunction of specialized neurons in the brain that should activate when observing other people. In typically-developing people, these mirror neurons are thought to perhaps play a major part in social learning and general comprehension of the actions of others.

Causes

The causes and etiology of autism are uncertain. Possible genetic and environmental causes are a common focus in published literature. Since autistic individuals are all somewhat different from one another, multiple "causes" have been proposed that interact with each other in subtle and complex ways, and thus give slightly differing outcomes in each individual.

Research claims also link autism with abnormal blood vessel function, and oxidative stress.

Genetic component

Genetic influence comprises a significant aspect of research in the causes of autism. A large database showing theoretical links between autism and genetic loci summarises research indicating that the genetic influence may extend to every human chromosome. It has been observed in one twin-study in Britain that there was about a 60% concordance rate for autism in monozygotic (identical) twins, while dizygotic (non-identical) twins and other siblings comparatively exhibited about 4% concordance rates. Some research posits that the chances that an identical twin of an autistic person will also be autistic are 85-90%. The increased probabilities of siblings having autism has been calculated at about 35-fold more than normal.

Accompanying impairments are also a common feature of autism. Some people with autism also have gastrointestinal, immunological or neurological symptoms in addition to behavioral impairments. These associated complexes have also lead to the search for specific genetic connections and helped to focus on reasonable genetic implications.

Since genes provide the information for processes and structure at the level of the cell and its components during the growth and development of a human as well as maintenance during life, gene mutations (altered versions) and deletions (complete absence of genetic material) and possibly extra copies of genes would mean that the causes of autism begin very early. If a mutated gene fails to perform properly, then cells, proteins, enzymes and other crucial aspects of normal function may be significantly altered and operate incorrectly. Deletions could mean the complete absence of a sequence of events due to missing proteins or cell components for example. These genetic alterations and deletions will simply bring about a changed structure or process which effects a great many other needed structures and processes.

Another important aspect of research in genetic factors is environmental effects and the incidence of autism. During the lifetime of a person, gene mutations and deletions may be environmentally triggered or exacerbated. Conversely, it may also be that environment will not be a factor and nothing will change the autism characteristics. For autism, the answer to these possible explanations is still being researched and there is evidence that both may be true simply because there is more than one way a person may develop autism.

Extent of genetic origins of autism spectrum disorders: One hundred or more different genes have been implicated in the causes of autism spectrum disorders (ASD). The “glitches” or small changes in DNA are not genetic mutations, per se, but copy number variations (CNVs) which are extra copies or missing stretches of DNA. (In one case study a child with Asperger’s Syndrome was found to be missing a chain of 27 genes.) The extent of the possible genetic origins indicate that the abilities in social interaction and behavior, social and physical composure and impulse control are scattered throughout the human genome, implying that small genetic alterations, copies or deletions anywhere can have broad effects

Inheritability: Familial heritability may also be less prevalent than research to date implies. Spontaneous changes in DNA are much more common than is usual in other diseases with a genetic component. The sporadic form of the disease accounts for about 90% of affected individuals.

Environmental factors: Environmental factors such as mercury and radiation have been proposed as possible causes of ASD. However, the nature of the sporadic CNVs does not imply the presence of an environmental agent.

Comorbidity: Accompanying impairments are also a common feature of autism. Some people with autism also have gastrointestinal, immunological or neurological symptoms in addition to behavioral impairments. These associated complexes have also lead to the search for specific genetic connections and helped to focus on reasonable genetic implications.

Deletions and Mutations

Deleted genes have been noted as a probable influence or cause in autism. By locating specific missing genetic material the significance may be that specific genetic sites for autism controlling or causing autism (autism susceptibility alleles) may be located precisely. Another significant aspect of this research is that these deletions of genetic material indicate that autism may be established in some cases during meiosis (error-prone meiosis model) and this places the genesis of autism in some at the very beginning of life.

One very important question in this line of research is whether or not gene deletions are a cause or consequence of autism-susceptibility loci located elsewhere in the chromosomes.

Gene mutations may mean a gene does not function at all or does not function in the normal way. Since genes direct how the body grows and develops, mutations, like deletions, will effect a person at the most basic levels.

Mutation and deletion effects have been delineated in numerous research publications.

Correlated characteristics include global developmental delay, mild to severe delay of speech, social communication disorders and cognitive abilities, autistic like behaviour, high tolerance of pain, and repetitive mannerisms (e.g. chewing or mouthing).

Gene interaction may also complicate the causes leading to multiple genetic origins of autism, In a cascade like effect, when a gene loci is altered or omitted, others are effected due to change in interaction between genes and/or their functions.

Though not present in all individuals with autism, these mutations and deletions hold potential to point the way to more the genetic components of spectrum disorders. The research also advanced basic understanding in the genetic architecture of the genome of autistic individuals and will help in focusing future research.

One practical aspect of this type of research may be the development of a test that would confirm the autism diagnosis in children exhibiting symptoms and identify families who carry genetic defects that could be inherited by their children.

Other pervasive developmental disorders

Autism and Asperger's syndrome are just two of the five pervasive developmental disorders (PDDs). The three other pervasive developmental disorders are Rett syndrome, Childhood disintegrative disorder, and Pervasive developmental disorder not otherwise specified. Some of these are related to autism, while some of them are entirely separate conditions.