Autism

Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old.^[1] Autism affects information processing in the brain by altering how nerve cells and their synapses connect and organize; how this occurs is not well understood.^[2] It is one of three recognized disorders in the autism spectrum (ASDs), the other two being Asperger syndrome, which lacks delays in cognitive development and language, and Pervasive Developmental Disorder-Not Otherwise Specified (commonly abbreviated as PDD-NOS), which is diagnosed when the full set of criteria for autism or Asperger syndrome are not met.^[3]

Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by rare mutations, or by rare combinations of common genetic variants.^[4] In rare cases, autism is strongly associated with agents that cause birth defects.^[5] Controversies surround other proposed environmental causes, such as heavy metals, pesticides or childhood vaccines;^[6] the vaccine hypotheses are biologically implausible and lack convincing scientific evidence.^[7] The prevalence of autism is about 1–2 per 1,000 people; the prevalence of ASD is about 6 per 1,000, with about four times as many males as females. The number of people diagnosed with autism has increased dramatically since the 1980s, partly due to changes in diagnostic practice; the question of whether actual prevalence has increased is unresolved.^[8]

Parents usually notice signs in the first two years of their child's life.^[9] The signs usually develop gradually, but some autistic children first develop more normally and then regress.^[10] Although early behavioral or cognitive intervention can help autistic children gain self-care, social, and communication skills, there is no known cure.^[9] Not many children with autism live independently after reaching adulthood, though some become successful.^[11] An autistic culture has developed, with some individuals seeking a cure and others believing autism should be accepted as a difference and not treated as a disorder.^[12] 
Characteristics

Autism is a highly variable neurodevelopmental disorder^[13] that first appears during infancy or childhood, and generally follows a steady course without remission.^[14] Overt symptoms gradually begin after the age of six months, become established by age two or three years,^[15] and tend to continue through adulthood, although often in more muted form.^[16] It is distinguished not by a single symptom, but by a characteristic triad of symptoms: impairments in social interaction; impairments in communication; and restricted interests and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis.^[17] Autism's individual symptoms occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits.^[18] 
Social development
Social deficits distinguish autism and the related autism spectrum disorders (ASD; see Classification) from other developmental disorders.^[16] People with autism have social impairments and often lack the intuition about others that many people take for granted. Noted autistic Temple Grandin described her inability to understand the social communication of neurotypicals, or people with normal neural development, as leaving her feeling "like an anthropologist on Mars".^[19]

Unusual social development becomes apparent early in childhood. Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from social norms; for example, they have less eye contact and turn taking, and are more likely to communicate by manipulating another person's hand.^[20] Three- to five-year-old autistic children are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form attachments to their primary caregivers.^[21] Most autistic children display moderately less attachment security than non-autistic children, although this difference disappears in children with higher mental development or less severe ASD.^[22] Older children and adults with ASD perform worse on tests of face and emotion recognition.^[23]

Children with high-functioning autism suffer from more intense and frequent loneliness compared to non-autistic peers, despite the common belief that children with autism prefer to be alone. Making and maintaining friendships often proves to be difficult for those with autism. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect the quality of life more deeply.^[24]

There are many anecdotal reports, but few systematic studies, of aggression and violence in individuals with ASD. The limited data suggest that, in children with mental retardation, autism is associated with aggression, destruction of property, and tantrums. A 2007 study interviewed parents of 67 children with ASD and reported that about two-thirds of the children had periods of severe tantrums and about one-third had a history of aggression, with tantrums significantly more common than in non-autistic children with language impairments.^[25] A 2008 Swedish study found that, of individuals aged 15 or older discharged from hospital with a diagnosis of ASD, those who committed violent crimes were significantly more likely to have other psychopathological conditions such as psychosis.^[26] 
Communication
About a third to a half of individuals with autism do not develop enough natural speech to meet their daily communication needs.^[27] Differences in communication may be present from the first year of life, and may include delayed onset of babbling, unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, autistic children have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences, and are more likely to simply repeat others' words (echolalia)^[28][29] or reverse pronouns.^[30] Joint attention seems to be necessary for functional speech, and deficits in joint attention seem to distinguish infants with ASD:^[3] for example, they may look at a pointing hand instead of the pointed-at object,^[20][29] and they consistently fail to point at objects in order to comment on or share an experience.^[3] Autistic children may have difficulty with imaginative play and with developing symbols into language.^[28][29]

In a pair of studies, high-functioning autistic children aged 8–15 performed equally well as, and adults better than, individually matched controls at basic language tasks involving vocabulary and spelling. Both autistic groups performed worse than controls at complex language tasks such as figurative language, comprehension and inference. As people are often sized up initially from their basic language skills, these studies suggest that people speaking to autistic individuals are more likely to overestimate what their audience comprehends. 
Repetitive behavior

Autistic individuals display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R)^[32] categorizes as follows.

 A young boy with autism, and the

precise line of toys he made

• Stereotypy is repetitive movement, such as hand flapping, making sounds, head rolling, or body rocking.
• Compulsive behavior is intended and appears to follow rules, such as arranging objects in stacks or lines.
• Sameness is resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted.
• Ritualistic behavior involves an unvarying pattern of daily activities, such as an unchanging menu or a dressing ritual. This is closely associated with sameness and an independent validation has suggested combining the two factors.^[32]
• Restricted behavior is limited in focus, interest, or activity, such as preoccupation with a single television program, toy, or game.
• Self-injury includes movements that injure or can injure the person, such as eye poking, skin picking, hand biting, and head banging.^[3] A 2007 study reported that self-injury at some point affected about 30% of children with ASD.^[25]

No single repetitive or self-injurious behavior seems to be specific to autism, but only autism appears to have an elevated pattern of occurrence and severity of these behaviors.^[33] 
Other symptoms
Autistic individuals may have symptoms that are independent of the diagnosis, but that can affect the individual or the family.^[17] An estimated 0.5% to 10% of individuals with ASD show unusual abilities, ranging from splinter skills such as the memorization of trivia to the extraordinarily rare talents of prodigious autistic savants.^[34] Many individuals with ASD show superior skills in perception and attention, relative to the general population.^[35] Sensory abnormalities are found in over 90% of those with autism, and are considered core features by some,^[36] although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.^[37] Differences are greater for under-responsivity (for example, walking into things) than for over-responsivity (for example, distress from loud noises) or for sensation seeking (for example, rhythmic movements).^[38] An estimated 60%–80% of autistic people have motor signs that include poor muscle tone, poor motor planning, and toe walking;^[36] deficits in motor coordination are pervasive across ASD and are greater in autism proper.^[39]

Unusual eating behavior occurs in about three-quarters of children with ASD, to the extent that it was formerly a diagnostic indicator. Selectivity is the most common problem, although eating rituals and food refusal also occur;^[25] this does not appear to result in malnutrition. Although some children with autism also have gastrointestinal (GI) symptoms, there is a lack of published rigorous data to support the theory that autistic children have more or different GI symptoms than usual;^[40] studies report conflicting results, and the relationship between GI problems and ASD is unclear.^[41]

Parents of children with ASD have higher levels of stress.^[42] Siblings of children with ASD report greater admiration of and less conflict with the affected sibling than siblings of unaffected children or those with Down syndrome; siblings of individuals with ASD have greater risk of negative well-being and poorer sibling relationships as adults.^[43] 
Classification
Autism is one of the five pervasive developmental disorders (PDD), which are characterized by widespread abnormalities of social interactions and communication, and severely restricted interests and highly repetitive behavior.^[14] These symptoms do not imply sickness, fragility, or emotional disturbance.^[16]

Of the five PDD forms, Asperger syndrome is closest to autism in signs and likely causes; Rett syndrome and childhood disintegrative disorder share several signs with autism, but may have unrelated causes; PDD not otherwise specified (PDD-NOS; also called atypical autism) is diagnosed when the criteria are not met for a more specific disorder.^[44] Unlike with autism, people with Asperger syndrome have no substantial delay in language development.^[1] The terminology of autism can be bewildering, with autism, Asperger syndrome and PDD-NOS often called the autism spectrum disorders (ASD)^[9] or sometimes the autistic disorders,^[45] whereas autism itself is often called autistic disorder, childhood autism, or infantile autism. In this article, autism refers to the classic autistic disorder; in clinical practice, though, autism, ASD, and PDD are often used interchangeably.^[46] ASD, in turn, is a subset of the broader autism phenotype, which describes individuals who may not have ASD but do have autistic-like traits, such as avoiding eye contact.^[47]

The manifestations of autism cover a wide spectrum, ranging from individuals with severe impairments—who may be silent, mentally disabled, and locked into hand flapping and rocking—to high functioning individuals who may have active but distinctly odd social approaches, narrowly focused interests, and verbose, pedantic communication.^[48] Because the behavior spectrum is continuous, boundaries between diagnostic categories are necessarily somewhat arbitrary.^[36] Sometimes the syndrome is divided into low-, medium- or high-functioning autism (LFA, MFA, and HFA), based on IQ thresholds,^[49] or on how much support the individual requires in daily life; these subdivisions are not standardized and are controversial. Autism can also be divided into syndromal and non-syndromal autism; the syndromal autism is associated with severe or profound mental retardation or a congenital syndrome with physical symptoms, such as tuberous sclerosis.^[50] Although individuals with Asperger syndrome tend to perform better cognitively than those with autism, the extent of the overlap between Asperger syndrome, HFA, and non-syndromal autism is unclear.^[51]

Some studies have reported diagnoses of autism in children due to a loss of language or social skills, as opposed to a failure to make progress, typically from 15 to 30 months of age. The validity of this distinction remains controversial; it is possible that regressive autism is a specific subtype,^{[10][20][28][52]} or that there is a continuum of behaviors between autism with and without regression.^[53]

Research into causes has been hampered by the inability to identify biologically meaningful subpopulations^[54] and by the traditional boundaries between the disciplines of psychiatry, psychology, neurology and pediatrics.^[55] Newer technologies such as fMRI and diffusion tensor imaging can help identify biologically relevant phenotypes (observable traits) that can be viewed on brain scans, to help further neurogenetic studies of autism;^[56] one example is lowered activity in the fusiform face area of the brain, which is associated with impaired perception of people versus objects.^[2] It has been proposed to classify autism using genetics as well as behavior.^[57] 
Causes
Main article: Causes of autism

It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism's characteristic triad of symptoms.^[58] However, there is increasing suspicion that autism is instead a complex disorder whose core aspects have distinct causes that often co-occur.^[58][59]

Deletion (1), duplication (2) and inversion (3) are all chromosome abnormalities that have been implicated in autism.^[60]

Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by rare mutations with major effects, or by rare multigene interactions of common genetic variants.^[4][61] Complexity arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA but are heritable and influence gene expression.^[16] Studies of twins suggest that heritability is 0.7 for autism and as high as 0.9 for ASD, and siblings of those with autism are about 25 times more likely to be autistic than the general population.^[36] However, most of the mutations that increase autism risk have not been identified. Typically, autism cannot be traced to a Mendelian (single-gene) mutation or to a single chromosome abnormality like fragile X syndrome, and none of the genetic syndromes associated with ASDs has been shown to selectively cause ASD.^[4] Numerous candidate genes have been located, with only small effects attributable to any particular gene.^[4] The large number of autistic individuals with unaffected family members may result from copy number variations—spontaneous deletions or duplications in genetic material during meiosis.^[62] Hence, a substantial fraction of autism cases may be traceable to genetic causes that are highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome.^[60]

Several lines of evidence point to synaptic dysfunction as a cause of autism.^[2] Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion.^[63] Gene replacement studies in mice suggest that autistic symptoms are closely related to later developmental steps that depend on activity in synapses and on activity-dependent changes.^[64] All known teratogens (agents that cause birth defects) related to the risk of autism appear to act during the first eight weeks from conception, and though this does not exclude the possibility that autism can be initiated or affected later, it is strong evidence that autism arises very early in development.^[5] Although evidence for other environmental causes is anecdotal and has not been confirmed by reliable studies,^[6] extensive searches are underway.^[65] Environmental factors that have been claimed to contribute to or exacerbate autism, or may be important in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, vaccines^[8], and prenatal stress^[66], although no links have been found, and some have been completely dis-proven. Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and this has given rise to theories that vaccines or their preservatives cause autism, which was fueled by a scientific study which has since been proven to have been falsified. Although these theories lack convincing scientific evidence and are biologically implausible, parental concern about autism has led to lower rates of childhood immunizations and higher likelihood of measles outbreaks in some areas. 
Mechanism

Autism's symptoms result from maturation-related changes in various systems of the brain. How autism occurs is not well understood. Its mechanism can be divided into two areas: the pathophysiology of brain structures and processes associated with autism, and the neuropsychological linkages between brain structures and behaviors.^[67] The behaviors appear to have multiple pathophysiologies.^[18] 
Diagnosis

Diagnosis is based on behavior, not cause or mechanism.^[18][108] Autism is defined in the DSM-IV-TR as exhibiting at least six symptoms total, including at least two symptoms of qualitative impairment in social interaction, at least one symptom of qualitative impairment in communication, and at least one symptom of restricted and repetitive behavior. Sample symptoms include lack of social or emotional reciprocity, stereotyped and repetitive use of language or idiosyncratic language, and persistent preoccupation with parts of objects. Onset must be prior to age three years, with delays or abnormal functioning in either social interaction, language as used in social communication, or symbolic or imaginative play. The disturbance must not be better accounted for by Rett syndrome or childhood disintegrative disorder.^[1] ICD-10 uses essentially the same definition.^[14]

Several diagnostic instruments are available. Two are commonly used in autism research: the Autism Diagnostic Interview-Revised (ADI-R) is a semistructured parent interview, and the Autism Diagnostic Observation Schedule (ADOS) uses observation and interaction with the child. The Childhood Autism Rating Scale (CARS) is used widely in clinical environments to assess severity of autism based on observation of children.^[20]

A pediatrician commonly performs a preliminary investigation by taking developmental history and physically examining the child. If warranted, diagnosis and evaluations are conducted with help from ASD specialists, observing and assessing cognitive, communication, family, and other factors using standardized tools, and taking into account any associated medical conditions.^[109] A pediatric neuropsychologist is often asked to assess behavior and cognitive skills, both to aid diagnosis and to help recommend educational interventions.^[110] A differential diagnosis for ASD at this stage might also consider mental retardation, hearing impairment, and a specific language impairment^[109] such as Landau–Kleffner syndrome.^[111] The presence of autism can make it harder to diagnose coexisting psychiatric disorders such as depression.^[112]

Clinical genetics evaluations are often done once ASD is diagnosed, particularly when other symptoms already suggest a genetic cause.^[46] Although genetic technology allows clinical geneticists to link an estimated 40% of cases to genetic causes,^[113] consensus guidelines in the U.S. and UK are limited to high-resolution chromosome and fragile X testing.^[46] A genotype-first model of diagnosis has been proposed, which would routinely assess the genome's copy number variations.^[114] As new genetic tests are developed several ethical, legal, and social issues will emerge. Commercial availability of tests may precede adequate understanding of how to use test results, given the complexity of autism's genetics.^[115] Metabolic and neuroimaging tests are sometimes helpful, but are not routine.^[46]

ASD can sometimes be diagnosed by age 14 months, although diagnosis becomes increasingly stable over the first three years of life: for example, a one-year-old who meets diagnostic criteria for ASD is less likely than a three-year-old to continue to do so a few years later.^[52] In the UK the National Autism Plan for Children recommends at most 30 weeks from first concern to completed diagnosis and assessment, though few cases are handled that quickly in practice.^[109] A 2009 U.S. study found the average age of formal ASD diagnosis was 5.7 years, far above recommendations, and that 27% of children remained undiagnosed at age 8 years.^[116] Although the symptoms of autism and ASD begin early in childhood, they are sometimes missed; years later, adults may seek diagnoses to help them or their friends and family understand themselves, to help their employers make adjustments, or in some locations to claim disability living allowances or other benefits.^[117]

Underdiagnosis and overdiagnosis are problems in marginal cases, and much of the recent increase in the number of reported ASD cases is likely due to changes in diagnostic practices. The increasing popularity of drug treatment options and the expansion of benefits has given providers incentives to diagnose ASD, resulting in some overdiagnosis of children with uncertain symptoms. Conversely, the cost of screening and diagnosis and the challenge of obtaining payment can inhibit or delay diagnosis.^[118] It is particularly hard to diagnose autism among the visually impaired, partly because some of its diagnostic criteria depend on vision, and partly because autistic symptoms overlap with those of common blindness syndromes or blindisms.

History

A few examples of autistic symptoms and treatments were described long before autism was named. The Table Talk of Martin Luther contains the story of a 12-year-old boy who may have been severely autistic.^[162] According to Luther's notetaker Mathesius, Luther thought the boy was a soulless mass of flesh possessed by the devil, and suggested that he be suffocated.^[163] The earliest well-documented case of autism is that of Hugh Blair of Borgue, as detailed in a 1747 court case in which his brother successfully petitioned to annul Blair's marriage to gain Blair's inheritance.^[164] The Wild Boy of Aveyron, a feral child caught in 1798, showed several signs of autism; the medical student Jean Itard treated him with a behavioral program designed to help him form social attachments and to induce speech via imitation.^[165]

The New Latin word autismus (English translation autism) was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word autós (αὐτός, meaning self), and used it to mean morbid self-admiration, referring to "autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance".^[166]

Leo Kanner introduced the label early infantile autism in 1943.

The word autism first took its modern sense in 1938 when Hans Asperger of the Vienna University Hospital adopted Bleuler's terminology autistic psychopaths in a lecture in German about child psychology.^[167] Asperger was investigating an ASD now known as Asperger syndrome, though for various reasons it was not widely recognized as a separate diagnosis until 1981.^[165] Leo Kanner of the Johns Hopkins Hospital first used autism in its modern sense in English when he introduced the label early infantile autism in a 1943 report of 11 children with striking behavioral similarities.^[30] Almost all the characteristics described in Kanner's first paper on the subject, notably "autistic aloneness" and "insistence on sameness", are still regarded as typical of the autistic spectrum of disorders.^[59] It is not known whether Kanner derived the term independently of Asperger.^[168]

Kanner's reuse of autism led to decades of confused terminology like infantile schizophrenia, and child psychiatry's focus on maternal deprivation led to misconceptions of autism as an infant's response to "refrigerator mothers". Starting in the late 1960s autism was established as a separate syndrome by demonstrating that it is lifelong, distinguishing it from mental retardation and schizophrenia and from other developmental disorders, and demonstrating the benefits of involving parents in active programs of therapy.^[169] As late as the mid-1970s there was little evidence of a genetic role in autism; now it is thought to be one of the most heritable of all psychiatric conditions.^[170] Although the rise of parent organizations and the destigmatization of childhood ASD have deeply affected how we view ASD,^[165] parents continue to feel social stigma in situations where their autistic children's behaviors are perceived negatively by others,^[171] and many primary care physicians and medical specialists still express some beliefs consistent with outdated autism research.^[172]

The Internet has helped autistic individuals bypass nonverbal cues and emotional sharing that they find so hard to deal with, and has given them a way to form online communities and work remotely.^[173] Sociological and cultural aspects of autism have developed: some in the community seek a cure, while others believe that autism is simply another way of being.