Casuses

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.^[50] However, there is increasing suspicion that autism is instead a complex disorder whose core aspects have distinct causes that often co-occur.^[50][51]

Deletion (1), duplication (2) and inversion (3) are all chromosome abnormalities that have been implicated in autism.^[52]

Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by raremutations with major effects, or by rare multigene interactions of common genetic variants.^[5][53] 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.^[22] 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.^[42] 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, and none of the genetic syndromes associated with ASDs have been shown to selectively cause ASD.^[5] Numerous candidate genes have been located, with only small effects attributable to any particular gene.^[5] 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.^[54] 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.^[52]

Several lines of evidence point to synaptic dysfunction as a cause of autism.^[3] Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion.^[55] 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.^[56] 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, there is strong evidence that autism arises very early in development.^[6]

Although evidence for other environmental causes is anecdotal and has not been confirmed by reliable studies,^[7] extensive searches are underway.^[57] 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,^[9] and prenatal stress,^[58] although no links have been found, and some have been completely disproven.

Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination. This has led to unsupported theories blaming vaccine "overload", avaccine preservative, or the MMR vaccine for causing autism.^[8] The latter theory was supported by a litigation-funded study that has since been shown to have been "an elaborate fraud".^[59] Although these theories lack convincing scientific evidence and are biologically implausible,^[8] parental concern about a potential vaccine link with autism has led to lower rates of childhood immunizations, outbreaks of previously controlled childhood diseases in some countries, and the preventable deaths of several children.

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 intellectual disability, 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. 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. 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

Graphics and Statistics

History

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. 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.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. 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.

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".

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. 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. 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. 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. It is not known whether Kanner derived the term independently of Asperger.

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 intellectual disability and schizophrenia and from other developmental disorders, and demonstrating the benefits of involving parents in active programs of therapy. 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. Although the rise of parent organizations and the destigmatization of childhood ASD have deeply affected how we view ASD, parents continue to feel social stigma in situations where their autistic children's behaviors are perceived negatively by others, 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. 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.

Autism

Autism spectrum disorder (ASD) and autism are both general terms for a group of complex disorders of brain development. These disorders are characterized, in varying degrees, by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. With the May 2013 publication of the DSM-5 diagnostic manual all autism disorders were merged into one umbrella diagnosis of ASD. Previously, they were recognized as distinct subtypes, including autistic disorder, childhood disintegrative disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS) and Asperger syndrome. 

ASD can be associated with intellectual disability, difficulties in motor coordination and attention and physical health issues such as sleep and gastrointestinal disturbances. Some persons with ASD excel in visual skills, music, math and art.

Autism appears to have its roots in very early brain development. However, the most obvious signs of autism and symptoms of autism tend to emerge between 2 and 3 years of age. Autism Speaks continues to fund research on effective methods for earlier diagnosis, as early intervention with proven behavioral therapies can improve outcomes. Increasing autism awareness is a key aspect of this work and one in which our families and volunteers play an invaluable role.