Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. The diagnostic criteria require that symptoms become apparent before a child is three years old.[2] 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.[3] 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.[4]

 

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.[5] In rare cases, autism is strongly associated with agents that cause birth defects.[6] Controversies surround other proposed environmental causes, such as heavy metals, pesticides or childhood vaccines;[7] the vaccine hypotheses are biologically implausible and lack convincing scientific evidence.[8] The prevalence of autism is about 1–2 per 1,000 people worldwide, and the Centers for Disease Control and Prevention (CDC) report 11 per 1,000 children in the United States are diagnosed with ASD as of 2008.[7][9][10] 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.[11]

 

Parents usually notice signs in the first two years of their child's life.[12] The signs usually develop gradually, but some autistic children first develop more normally and then regress.[13] Early behavioral or cognitive intervention can help autistic children gain self-care, social, and communication skills.[12] Although there is no known cure,[12] there have been reported cases of children who recovered.[14] Not many children with autism live independently after reaching adulthood, though some become successful.[15] 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.[16]

 

Contents

 1 Characteristics 1.1 Social development

 1.2 Communication

 1.3 Repetitive behavior

 1.4 Other symptoms

 

2 Classification

 3 Causes

 4 Mechanism 4.1 Pathophysiology

 4.2 Neuropsychology

 

5 Screening

 6 Diagnosis

 7 Management

 8 Prognosis

 9 Epidemiology

 10 History

 11 References

 12 External links

 

Characteristics

 

Autism is a highly variable neurodevelopmental disorder[17] that first appears during infancy or childhood, and generally follows a steady course without remission.[18] Overt symptoms gradually begin after the age of six months, become established by age two or three years,[19] and tend to continue through adulthood, although often in more muted form.[20] 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.[21] 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.[22]

 

Social development

 

Social deficits distinguish autism and the related autism spectrum disorders (ASD; see Classification) from other developmental disorders.[20] 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".[23]

 

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 do not have the ability to use simple movements to express themselves, such as the deficiency to point at things.[24] 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.[25] 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.[26] Older children and adults with ASD perform worse on tests of face and emotion recognition.[27]

 

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.[28]

 

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.[29] 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.[30]

 

 

Two major categories of cognitive theories have been proposed about the links between autistic brains and behavior.

 

The first category focuses on deficits in social cognition. The empathizing–systemizing theory postulates that autistic individuals can systemize—that is, they can develop internal rules of operation to handle events inside the brain—but are less effective at empathizing by handling events generated by other agents. An extension, the extreme male brain theory, hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing;[103] this extension is controversial, as many studies contradict the idea that baby boys and girls respond differently to people and objects 

These theories are somewhat related to the earlier theory of mind approach, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others. The theory of mind hypothesis is supported by autistic children's atypical responses to the Sally–Anne test for reasoning about others' motivations  and the mirror neuron system theory of autism described in Pathophysiology maps well to the hypothesis  However, most studies have found no evidence of impairment in autistic individuals' ability to understand other people's basic intentions or goals; instead, data suggests that impairments are found in understanding more complex social emotions or in considering others' viewpoints 

The second category focuses on nonsocial or general processing. Executive dysfunction hypothesizes that autistic behavior results in part from deficits in working memory, planning, inhibition, and other forms of executive function.[106] Tests of core executive processes such as eye movement tasks indicate improvement from late childhood to adolescence, but performance never reaches typical adult levels ] A strength of the theory is predicting stereotyped behavior and narrow interests  two weaknesses are that executive function is hard to measure and that executive function deficits have not been found in young autistic children 

Weak central coherence theory hypothesizes that a limited ability to see the big picture underlies the central disturbance in autism. One strength of this theory is predicting special talents and peaks in performance in autistic people.[109] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals ] These theories map well from the underconnectivity theory of autism.

  

 

 

 

Neither category is satisfactory on its own; social cognition theories poorly address autism's rigid and repetitive behaviors, while the nonsocial theories have difficulty explaining social impairment and communication difficulties.[62] A combined theory based on multiple deficits may prove to be more useful 

Screening

 

About half of parents of children with ASD notice their child's unusual behaviors by age 18 months, and about four-fifths notice by age 24 months.[55] According to an article in the Journal of Autism and Developmental Disorders, failure to meet any of the following milestones "is an absolute indication to proceed with further evaluations. Delay in referral for such testing may delay early diagnosis and treatment and affect the long-term outcome  No babbling by 12 months.

 No gesturing (pointing, waving bye-bye, etc.) by 12 months.

 No single words by 16 months.

 No two-word (spontaneous, not just echolalic) phrases by 24 months.

 Any loss of any language or social skills, at any age.

 

US and Japanese practice is to screen all children for ASD at 18 and 24 months, using autism-specific formal screening tests. In contrast, in the UK, children whose families or doctors recognize possible signs of autism are screened. It is not known which approach is more effective  Screening tools include the Modified Checklist for Autism in Toddlers (M-CHAT), the Early Screening of Autistic Traits Questionnaire, and the First Year Inventory; initial data on M-CHAT and its predecessor CHAT on children aged 18–30 months suggests that it is best used in a clinical setting and that it has low sensitivity (many false-negatives) but good specificity (few false-positives).[55] It may be more accurate to precede these tests with a broadband screener that does not distinguish ASD from other developmental disorders.[112] Screening tools designed for one culture's norms for behaviors like eye contact may be inappropriate for a different culture.[113] Although genetic screening for autism is generally still impractical, it can be considered in some cases, such as children with neurological symptoms and dysmorphic features 

Diagnosis

 

Diagnosis is based on behavior, not cause or mechanism 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  ICD-10 uses essentially the same definition 

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 

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  A pediatric neuropsychologist is often asked to assess behavior and cognitive skills, both to aid diagnosis and to help recommend educational interventions  A differential diagnosis for ASD at this stage might also consider mental retardation, hearing impairment, and a specific language impairment[  such as Landau–Kleffner syndrome  The presence of autism can make it harder to diagnose coexisting psychiatric disorders such as depression 

Clinical genetics evaluations are often done once ASD is diagnosed, particularly when other symptoms already suggest a genetic cause Although genetic technology allows clinical geneticists to link an estimated 40% of cases to genetic causes ] consensus guidelines in the US and UK are limited to high-resolution chromosome and fragile X testing.[1] A genotype-first model of diagnosis has been proposed, which would routinely assess the genome's copy number variations  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 Metabolic and neuroimaging tests are sometimes helpful, but are not routine 

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 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  A 2009 US 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.[124] 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 

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 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 

 

 

Pathophysiology

 

Autism affects the amygdala, cerebellum, and many other parts of the brain.[73]

Unlike many other brain disorders, such as Parkinson's, autism does not have a clear unifying mechanism at either the molecular, cellular, or systems level; it is not known whether autism is a few disorders caused by mutations converging on a few common molecular pathways, or is (like intellectual disability) a large set of disorders with diverse mechanisms.[17] Autism appears to result from developmental factors that affect many or all functional brain systems,[74] and to disturb the timing of brain development more than the final product.[73] Neuroanatomical studies and the associations with teratogens strongly suggest that autism's mechanism includes alteration of brain development soon after conception.[6] This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors.[75] Just after birth, the brains of autistic children tend to grow faster than usual, followed by normal or relatively slower growth in childhood. It is not known whether early overgrowth occurs in all autistic children. It seems to be most prominent in brain areas underlying the development of higher cognitive specialization.[40] Hypotheses for the cellular and molecular bases of pathological early overgrowth include the following:

 An excess of neurons that causes local overconnectivity in key brain regions.[76]

 Disturbed neuronal migration during early gestation.[77][78]

 Unbalanced excitatory–inhibitory networks.[78]

 Abnormal formation of synapses and dendritic spines,[78] for example, by modulation of the neurexin–neuroligin cell-adhesion system,[79] or by poorly regulated synthesis of synaptic proteins.[80][81] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated.[82]

 

Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. Aberrant immune activity during critical periods of neurodevelopment is possibly part of the mechanism of some forms of ASD.[83] Although some abnormalities in the immune system have been found in specific subgroups of autistic individuals, it is not known whether these abnormalities are relevant to or secondary to autism's disease processes.[84] As autoantibodies are found in conditions other than ASD, and are not always present in ASD,[85] the relationship between immune disturbances and autism remains unclear and controversial.[77]

 

The relationship of neurochemicals to autism is not well understood; several have been investigated, with the most evidence for the role of serotonin and of genetic differences in its transport.[3] The role of group I metabotropic glutamate receptors (mGluR) in the pathogenesis of fragile X syndrome, the most common identified genetic cause of autism, has led to interest in the possible implications for future autism research into this pathway.[86] Some data suggest an increase in several growth hormones; other data argue for diminished growth factors.[87] Also, some inborn errors of metabolism are associated with autism, but probably account for less than 5% of cases.[88]

 

The mirror neuron system (MNS) theory of autism hypothesizes that distortion in the development of the MNS interferes with imitation and leads to autism's core features of social impairment and communication difficulties. The MNS operates when an animal performs an action or observes another animal perform the same action. The MNS may contribute to an individual's understanding of other people by enabling the modeling of their behavior via embodied simulation of their actions, intentions, and emotions.[89] Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with Asperger syndrome, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD.[90] However, individuals with autism also have abnormal brain activation in many circuits outside the MNS[91] and the MNS theory does not explain the normal performance of autistic children on imitation tasks that involve a goal or object.[92]

 

Autistic individuals tend to use different areas of the brain (yellow) for a movement task compared to a control group (blue).[93]

ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks.[94] In autism there is evidence for reduced functional connectivity of the default network, a large-scale brain network involved in social and emotional processing, with intact connectivity of the task-positive network, used in sustained attention and goal-directed thinking. In people with autism the two networks are not negatively correlated in time, suggesting an imbalance in toggling between the two networks, possibly reflecting a disturbance of self-referential thought.[95] A 2008 brain-imaging study found a specific pattern of signals in the cingulate cortex which differs in individuals with ASD.[96]

 

The underconnectivity theory of autism hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[97] Evidence for this theory has been found in functional neuroimaging studies on autistic individuals[35] and by a brainwave study that suggested that adults with ASD have local overconnectivity in the cortex and weak functional connections between the frontal lobe and the rest of the cortex.[98] Other evidence suggests the underconnectivity is mainly within each hemisphere of the cortex and that autism is a disorder of the association cortex.[99]

 

From studies based on event-related potentials, transient changes to the brain's electrical activity in response to stimuli, there is considerable evidence for differences in autistic individuals with respect to attention, orientiation to auditory and visual stimuli, novelty detection, language and face processing, and information storage; several studies have found a preference for nonsocial stimuli.[100] For example, magnetoencephalography studies have found evidence in autistic children of delayed responses in the brain's processing of auditory signals.[101]

 

In the genetic area, relations have been found between autism and schizophrenia based on duplications and deletions of chromosomes; research showed that schizophrenia and autism are significantly more common in combination with 1q21.1 deletion syndrome. Research on autism/schizophrenia relations for chromosome 15 (15q13.3), chromosome 16 (16p13.1) and chromosome 17 (17p12) are inconclusive.[102]

 

Epidemiology

 

Main article: Epidemiology of autism

 

Reports of autism cases per 1,000 children grew dramatically in the US from 1996 to 2007. It is unknown how much, if any, growth came from changes in autism's prevalence.

Most recent reviews tend to estimate a prevalence of 1–2 per 1,000 for autism and close to 6 per 1,000 for ASD,[11] and 11 per 1,000 children in the United States for ASD as of 2008;[10][157] because of inadequate data, these numbers may underestimate ASD's true prevalence.[1] PDD-NOS's prevalence has been estimated at 3.7 per 1,000, Asperger syndrome at roughly 0.6 per 1,000, and childhood disintegrative disorder at 0.02 per 1,000.[158] The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness,[158][159] though unidentified environmental risk factors cannot be ruled out.[7] The available evidence does not rule out the possibility that autism's true prevalence has increased;[158] a real increase would suggest directing more attention and funding toward changing environmental factors instead of continuing to focus on genetics.[68]

 

Boys are at higher risk for ASD than girls. The sex ratio averages 4.3:1 and is greatly modified by cognitive impairment: it may be close to 2:1 with mental retardation and more than 5.5:1 without.[11] Although the evidence does not implicate any single pregnancy-related risk factor as a cause of autism, the risk of autism is associated with advanced age in either parent, and with diabetes, bleeding, and use of psychiatric drugs in the mother during pregnancy.[160] The risk is greater with older fathers than with older mothers; two potential explanations are the known increase in mutation burden in older sperm, and the hypothesis that men marry later if they carry genetic liability and show some signs of autism.[40] Most professionals believe that race, ethnicity, and socioeconomic background do not affect the occurrence of autism.[161]

 

Several other conditions are common in children with autism.[3] They include:

 Genetic disorders. About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome,[162] and ASD is associated with several genetic disorders.[163]

 Mental retardation. The fraction of autistic individuals who also meet criteria for mental retardation has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing autistic intelligence.[164] For ASD other than autism, the association with mental retardation is much weaker.[165]

 Anxiety disorders are common among children with ASD; there are no firm data, but studies have reported prevalences ranging from 11% to 84%. Many anxiety disorders have symptoms that are better explained by ASD itself, or are hard to distinguish from ASD's symptoms.[166]

 Epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder.[167]

 Several metabolic defects, such as phenylketonuria, are associated with autistic symptoms.[88]

 Minor physical anomalies are significantly increased in the autistic population.[168]

 Preempted diagnoses. Although the DSM-IV rules out concurrent diagnosis of many other conditions along with autism, the full criteria for Attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and other of these conditions are often present and these comorbid diagnoses are increasingly accepted.[169]

 Sleep problems affect about two-thirds of individuals with ASD at some point in childhood. These most commonly include symptoms of insomnia such as difficulty in falling asleep, frequent nocturnal awakenings, and early morning awakenings. Sleep problems are associated with difficult behaviors and family stress, and are often a focus of clinical attention over and above the primary ASD diagnosis.[170]

 

History

 

Further information: History of Asperger syndrome and Sociological and cultural aspects of autism

 

Leo Kanner introduced the label early infantile autism in 1943.

A few examples of autistic symptoms and treatments were described long before autism was named. The Table Talk of Martin Luther, compiled by his notetaker, Mathesius, contains the story of a 12-year-old boy who may have been severely autistic.[171] Luther reportedly thought the boy was a soulless mass of flesh possessed by the devil, and suggested that he be suffocated, although a later critic has cast doubt on the veracity of this report.[172] 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.[173] 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.[174]

 

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".[175]

 

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.[176] 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.[174] 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.[34] 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.[62] It is not known whether Kanner derived the term independently of Asperger.[177]

 

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.[178] 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.[179] Although the rise of parent organizations and the destigmatization of childhood ASD have deeply affected how we view ASD,[174] parents continue to feel social stigma in situations where their autistic children's behaviors are perceived negatively by others,[180] and many primary care physicians and medical specialists still express some beliefs consistent with outdated autism research 

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.[182] 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.[