Autism spectrum

Before the DSM-5 (2013) and ICD-11 (2022) diagnostic manuals were adopted, what is now called ASD was found under the diagnostic category pervasive developmental disorder. The previous system relied on a set of closely related and overlapping diagnoses such as Asperger syndrome and Kanner syndrome. This created unclear boundaries between the terms, so for the DSM-5 and ICD-11, a spectrum approach was taken. The new system is also more restrictive, meaning fewer people now qualify for diagnosis.[24]

The DSM-5 and ICD-11 use different categorization tools to define this spectrum. DSM-5 uses a "level" system, which ranks how in need of support the patient is,[25] while the ICD-11 system has two axes, intellectual impairment and language impairment,[26] as these are seen as the most crucial factors.

It is now known that autism is a highly variable neurodevelopmental disorder[27] that is generally thought to cover a broad and deep spectrum, manifesting very differently from one person to another. Some have high support needs, may be non-speaking, and experience developmental delays; this is more likely with other co-existing diagnoses. Others have relatively low support needs; they may have more typical speech-language and intellectual skills but atypical social/conversation skills, narrowly focused interests, and wordy, pedantic communication.[28] They may still require significant support in some areas of their lives. The spectrum model should not be understood as a continuum running from mild to severe, but instead means that autism can present very differently in each person.[29] How a person presents can depend on context, and may vary over time.[30]

While the DSM and ICD greatly influence each other, there are also differences. For example, Rett syndrome was included in ASD in the DSM-5, but in the ICD-11 it was excluded and placed in the chapter on Developmental Anomalies. The ICD and the DSM change over time, and there has been collaborative work toward a convergence of the two since 1980 (when DSM-III was published and ICD-9 was current), including more rigorous biological assessment—in place of historical experience—and a simplification of the classification system.[31][32][33][34]

The World Health Organization's International Classification of Diseases (11th Revision), ICD-11, was released in June 2018 and came into full effect as of January 2022.[35][31] It describes ASD as follows:[36]

Autism spectrum disorder is characterised by persistent deficits in the ability to initiate and to sustain reciprocal social interaction and social communication, and by a range of restricted, repetitive, and inflexible patterns of behaviour, interests or activities that are clearly atypical or excessive for the individual's age and sociocultural context. The onset of the disorder occurs during the developmental period, typically in early childhood, but symptoms may not become fully manifest until later, when social demands exceed limited capacities. Deficits are sufficiently severe to cause impairment in personal, family, social, educational, occupational or other important areas of functioning and are usually a pervasive feature of the individual's functioning observable in all settings, although they may vary according to social, educational, or other context. Individuals along the spectrum exhibit a full range of intellectual functioning and language abilities.

— ICD-11, chapter 6, section A02

ICD-11 was produced by professionals from 55 countries out of the 90 involved and is the most widely used reference worldwide.

The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), released in 2022, is the current version of the DSM. It is the predominant mental health diagnostic system used in the United States and Canada, and is often used in Anglophone countries.

Its fifth edition, DSM-5, released in May 2013, was the first to define ASD as a single diagnosis,[37] which is still the case in the DSM-5-TR.[38] ASD encompasses previous diagnoses, including the four traditional diagnoses of autism—classic Kanner syndrome, Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS)—and the range of diagnoses that included the word "autism".[39] Rather than distinguishing among these diagnoses, the DSM-5 and DSM-5-TR adopt a dimensional approach to diagnosing disorders that fall underneath the autism spectrum umbrella in one diagnostic category. Within this category, the DSM-5 and the DSM include a framework that differentiates each person by dimensions of symptom severity, as well as by associated features (i.e., the presence of other disorders or factors that likely contribute to the symptoms, other neurodevelopmental or mental disorders, intellectual disability, or language impairment).[38] The symptom domains are social communication and restricted, repetitive behaviors, with the option of a separate severity—the negative impact of the symptoms on the person—being specified for each domain, rather than an overall severity.[40] Before the DSM-5, the DSM separated social deficits and communication deficits into two domains.[41] Further, the DSM-5 changed to an onset age in the early developmental period, with a note that symptoms may manifest later when social demands exceed capabilities, rather than the previous, more restricted three years of age.[42] These changes remain in the DSM-5-TR.[38]

For many autistic people, characteristics first appear during infancy or childhood and follow a steady course without remission (different developmental timelines are described in more detail below).[43] Autistic people may be severely impaired in some respects but average, or even superior, in others.[44][45][46]

Clinicians consider assessment for ASD when a patient shows:

• regular difficulties in social interaction or communication
• restricted or repetitive behaviors (often called "stimming")
• resistance to changes or restricted interests

These features are typically assessed with the following, when appropriate:

• problems in obtaining or sustaining employment or education
• difficulties in initiating or sustaining social relationships
• connections with mental health or learning disability services
• a history of neurodevelopmental conditions (including learning disabilities and ADHD) or mental health conditions.[47][48]

There are many signs associated with autism; the presentation varies widely:[49][50]

Common signs for autistic spectrum disorder

avoidance of eye-contact little or no babbling as an infant not showing interest in indicated objects delayed language skills (e.g. having a smaller vocabulary than peers or difficulty expressing themselves in words) reduced interest in other children or caretakers, possibly with more interest in objects difficulty playing reciprocal games (e.g. peek-a-boo) hyper- or hypo-sensitivity to or unusual response to the smell, texture, sound, taste, or appearance of things resistance to changes in routine repetitive, limited, or otherwise unusual usage of toys (e.g. lining up toys) repetition of words or phrases (echolalia) repetitive motions or movements, including stimming self-harming

The broader autism phenotype (BAP) describes people who may not have ASD but do have autistic traits, such as avoiding eye contact and stimming.[51]

In social contexts, autistic people may respond and behave differently than people without ASD.[52]

Impairments in social skills present many challenges for autistic people. Deficits in social skills may lead to problems with friendships, romantic relationships, daily living, and vocational success.[53] One study that examined the outcomes of autistic adults found that, compared to the general population, autistic people were less likely to be married, but it is unclear whether this was because of deficits in social skills, intellectual impairment, or another reason.[54] One factor is likely discrimination against autistic people, which is perpetuated by misunderstandings[55]—for example, "empathy" has more meanings within psychology than in common parlance.[56] Autistic people do have compassion (affective empathy), and may find it easy to read other autistic people's feelings where there is similarity in presentation of symptoms. However, the condition features limited, though not necessarily absent, cognitive empathy[57] (see empathizing–systemizing theory) with the neurotypical majority, i.e. social naïvety,[58] lower than average intuitive perception of the utility or meaning of body language, social reciprocity,[59] and/or social expectations, including the habitus, social cues, and/or some aspects of sarcasm.[60] To some degree, this may be due to comorbid alexithymia.[61] As they progress through life, autistic people observe and form a model of social patterns, and develop coping mechanisms, referred to as "masking".[62][63] This limited intuition is bidirectional, in that studies imply neurotypical persons often have poor cognitive empathy with autistic people.[64][65][66]

Until 2013, deficits in social function and communication were considered two separate symptom domains of autism.[67] The current social communication domain criteria for autism diagnosis require people to have deficits across three social skills: social-emotional reciprocity, nonverbal communication, and developing and sustaining relationships.[38]

A range of social-emotional reciprocity difficulties (a person's ability to naturally engage in social interactions) may be present. Autistic people may lack mutual sharing of interests; many autistic children prefer not to play or interact with others. They may lack awareness or understanding of other people's thoughts or feelings: a child may get too close to peers (entering their personal space) without noticing that this makes them uncomfortable. They may also engage in atypical behaviors to gain attention: a child may push a peer to gain attention before starting a conversation.[68]

Older autistic children and adults perform worse on tests of face and emotion recognition than non-autistic people, although this may be due to the prevalence of alexithymia in autistic people rather than autism itself.[69]

Autistic people experience deficits in their ability to develop, maintain, and understand relationships, as well as difficulties adjusting behavior to fit social contexts.[70] ASD presents with impairments in pragmatic communication skills, such as difficulty initiating a conversation or failure to consider a listener's interests to sustain a conversation.[68] The ability to be focused exclusively on one topic in communication is known as monotropism, and can be compared to "tunnel vision". It is common for autistic people to communicate strong interest in a specific topic, speaking in lesson-like monologues about their passion instead of enabling reciprocal communication.[71] What may look like self-involvement or indifference to others stems from a struggle to recognize or remember that other people have their own personalities, perspectives, and interests.[72][73] Another difference in pragmatic communication skills is that autistic people may not recognize the need to control the volume of their voice in different social settings; for example, they may speak loudly in libraries or movie theaters.[74]

Autistic people display atypical nonverbal behaviors or have difficulties with nonverbal communication. They may make infrequent eye contact: an autistic person may not make eye contact when called by name, or may avoid eye contact with an observer. Aversion of gaze can also be seen in anxiety disorders, but poor eye contact in autistic children is not due to shyness or anxiety; rather, it is overall diminished in quantity. Autistic people may struggle with both production and understanding of facial expressions. They often do not know how to recognize emotions from others' facial expressions, or may not respond with appropriate facial expressions. They may have trouble recognizing subtle expressions of emotion and identifying what various emotions mean for the conversation.[75][71]

Temple Grandin in 2011

A defining feature is that autistic people have social impairments and often lack intuitions about others that many people take for granted. Temple Grandin, an autistic woman involved in autism activism, described her inability to understand the social communication of neurotypicals, or people with typical neural development, as leaving her feeling "like an anthropologist on Mars".[76] They may also not pick up on body language or social cues such as eye contact and facial expressions if they provide more information than the person can process at that time. They struggle with understanding the context and subtext of conversational or printed situations, and have trouble forming resulting conclusions about the content. This also results in a lack of social awareness and atypical language expression.[72] How facial expressions differ between those on the autism spectrum and neurotypical people is not clear.[77] Further, at least half of autistic children have unusual prosody.[74]

Autistic people may also experience difficulties with verbal communication. 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).[78] Joint attention seems to be necessary for functional speech, and deficits in joint attention seem to distinguish autistic infants.[79] For example, they may look at a pointing hand instead of the object to which the hand is pointing,[80][78] and they consistently fail to point at objects in order to comment on or share an experience.[79] Autistic children may have difficulty with imaginative play and with developing symbols into language.[78] Some autistic linguistic behaviors include repetitive or rigid language, and restricted interests in conversation. For example, a child might repeat words or insist on always talking about the same subject.[68] Echolalia may also be present in autistic people, for example by responding to a question by repeating the inquiry instead of answering.[71] Language impairment is also common in autistic children, but is not part of a diagnosis.[68] Many autistic children develop language skills at an uneven pace where they easily acquire some aspects of communication, while never fully developing others,[71] such as in some cases of hyperlexia. Some people remain completely nonverbal throughout their lives. The CDC estimated that around 40% of autistic children do not speak at all, although the accompanying levels of literacy and nonverbal communication skills vary.[81]

A young autistic boy who has arranged his toys in a row

ASD includes a wide variety of characteristics. Some of these include behavioral characteristics which widely range from slow development of social and learning skills to difficulties creating connections with other people. Autistic people may experience these challenges with forming connections due to anxiety or depression, which they are more likely to experience, and as a result isolate themselves.[82]

Other behavioral characteristics include abnormal responses to sensations (such as sights, sounds, touch, taste and smell) and problems keeping a consistent speech rhythm. The latter problem influences social skills, leading to potential problems in understanding for interlocutors. Autistic people's behavioral characteristics typically influence development, language, and social competence. Their behavioral characteristics can be observed as perceptual disturbances, disturbances of development rate, relating, speech and language, and motility.[83]

The second core symptom of autism spectrum is a pattern of restricted and repetitive behaviors, activities, and interests. In order to be diagnosed with ASD under the DSM-5-TR, a person must have at least two of the following behaviors:[38][84]

• 

  An older autistic boy arranging brads on a cork coaster.
  Repetitive behaviors – Repetitive behaviors such as rocking, hand flapping, finger flicking, head banging, or repeating phrases or sounds.[68] These behaviors may occur constantly or only when the person gets stressed, anxious or upset. These behaviors are also known as stimming.
• Resistance to change – A strict adherence to routines such as eating certain foods in a specific order or taking the same path to school every day.[68] The person may become distressed if there is a change or disruption to their routine.
• Restricted interests – An excessive interest in a particular activity, topic, or hobby, and devoting all their attention to it. For example, young children might completely focus on things that spin and ignore everything else. Older children might try to learn everything about a single topic, such as the weather or sports, and perseverate or talk about it constantly.[68]
• Sensory reactivity – An unusual reaction to certain sensory inputs such as having a negative reaction to specific sounds or textures, being fascinated by lights or movements or having an apparent indifference to pain or heat.[85]

Autistic people can display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R) categorizes as follows.[86]

• Stereotyped behaviors: Repetitive movements, such as hand flapping, head rolling, or body rocking.
• Compulsive behaviors: Time-consuming behaviors intended to reduce anxiety, that a person feels compelled to perform repeatedly or according to rigid rules, such as placing objects in a specific order, checking things, or handwashing.
• Sameness: Resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted.
• Ritualistic behavior: 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.[86]
• Restricted interests: Interests or fixations that are abnormal in theme or intensity of focus, such as preoccupation with a single television program, toy, or game.
• Self-injury: Behaviors such as eye-poking, skin-picking, hand-biting and head-banging.[79]

Self-injurious behaviors (SIB) are relatively common in autistic people, and can include head-banging, self-cutting, self-biting, and hair-pulling.[87] Some of these can result in serious injury or death.[87] Following are theories about the cause of self-injurious behavior in children with developmental delay, including autistic children:[88]

• Frequency and/or continuation of self-injurious behavior can be influenced by environmental factors (e.g. reward in return for halting self-injurious behavior). This theory does not apply to younger children with autism. There is some evidence that frequency of self-injurious behavior can be reduced by removing or modifying environmental factors that reinforce the behavior.[88]^: 10–12
• Higher rates of self-injury are also noted in socially isolated people with autism. Studies have shown that socialization skills are related factors to self-injurious behavior for people with autism.[89]
• Self-injury could be a response to modulate pain perception when chronic pain or other health problems that cause pain are present.[88]^: 12–13
• An abnormal basal ganglia connectivity may predispose to self-injurious behavior.[88]^: 13

The suicide rate for verbal autistics is nine times that of the general population.[90]

Autistic people may have symptoms that do not contribute to the official diagnosis, but that can affect the person or the family.[91]

• Some people with ASD show unusual or notable abilities, ranging from splinter skills (such as the memorization of trivia) to rare talents in mathematics, music, or artistic reproduction, which in exceptional cases are considered a part of the savant syndrome.[92][93][94] One study describes how some people with ASD show superior skills in perception and attention relative to the general population.[95] Sensory abnormalities are found in over 90% of autistic people, and are considered core features by some.[96]
• More generally, autistic people tend to show a "spiky skills profile", with strong abilities in some areas contrasting with much weaker abilities in others.[97]
• Differences between the previously recognized disorders under the autism spectrum 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).[98] An estimated 60–80% of autistic people have motor signs that include poor muscle tone, poor motor planning, and toe walking;[96][99] deficits in motor coordination are pervasive across ASD and are greater in autism proper.[100][101]
• Pathological demand avoidance can occur. People with this set of autistic symptoms are more likely to refuse to do what is asked or expected of them, even to activities they enjoy.
• Unusual or atypical eating behavior occurs in about three-quarters of children with ASD, to the extent that it was formerly a diagnostic indicator.[91] Selectivity is the most common problem, although eating rituals and food refusal also occur.[102]

Research into causes has been hampered by the inability to identify biologically meaningful subgroups within the autistic population[110] and by the traditional boundaries between the disciplines of psychiatry, psychology, neurology and pediatrics.[111] 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;[112] one example is lowered activity in the fusiform face area of the brain, which is associated with impaired perception of people versus objects.[113] It has been proposed to classify autism using genetics as well as behavior.[114]

Autism spectrum disorder (ASD) can be classified into two categories: "syndromic autism" and "non-syndromic autism."

Syndromic autism refers to cases where ASD is one of the characteristics associated with a broader medical condition or syndrome, representing about 25% of ASD cases. The causes of syndromic autism are often known, and monogenic disorders account for approximately 5% of these cases.

Non-syndromic autism, also known as classic or idiopathic autism, represents the majority of cases, and its cause is typically polygenic and unknown.

Hundreds of different genes are implicated in susceptibility to developing autism,[115] most of which alter the brain structure in a similar way

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 multi-gene interactions of common genetic variants.[116][117] Complexity arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA sequencing but are heritable and influence gene expression.[118] Many genes have been associated with autism through sequencing the genomes of affected people and their parents.[119] But 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 ASD have been shown to selectively cause ASD.[116] Numerous genes have been found, with only small effects attributable to any particular gene.[116] Most loci individually explain less than 1% of cases of autism.[120] As of 2018, it appeared that between 74% and 93% of ASD risk is heritable.[84] After an older child is diagnosed with ASD, 7% to 20% of subsequent children are likely to be as well.[84] If parents have one autistic child, they have a 2% to 8% chance of having a second child who is autistic. If the autistic child is an identical twin, the other will be affected 36% to 95% of the time. A fraternal twin is affected up to 31% of the time. The large number of autistic people with unaffected family members may result from spontaneous structural variation, such as deletions, duplications or inversions in genetic material during meiosis.[121][122] 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.[123]

As of 2018, understanding of genetic risk factors had shifted from a focus on a few alleles to an understanding that genetic involvement in ASD is probably diffuse, depending on a large number of variants, some of which are common and have a small effect, and some of which are rare and have a large effect. The most common gene disrupted with large effect rare variants appeared to be CHD8, but less than 0.5% of autistic people have such a mutation. The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8, which is a chromatin regulator enzyme that is essential during fetal development, CHD8 is an ATP dependent enzyme.[124][125][126] The protein contains an Snf2 helicase domain that is responsible for the hydrolysis of ATP to ADP.[126] CHD8 encodes for a DNA helicase that function as a transcription repressor by remodeling chromatin structure by altering the position of nucleosomes. CHD8 negatively regulates Wnt signaling. Wnt signaling is important in the vertebrate early development and morphogenesis. It is believed that CHD8 also recruits the linker histone H1 and causes the repression of β-catenin and p53 target genes.[124] The importance of CHD8 can be observed in studies where CHD8-knockout mice died after 5.5 embryonic days because of widespread p53 induced apoptosis. Some studies have determined the role of CHD8 in autism spectrum disorder (ASD). CHD8 expression significantly increases during human mid-fetal development.[124] The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology.[125] The developing mammalian brain has a conserved CHD8 target regions that are associated with ASD risk genes.[127] The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8.[128] Recently CD8 has been associated to the regulation of long non-coding RNAs (lncRNAs),[129] and the regulation of X chromosome inactivation (XCI) initiation, via regulation of Xist long non-coding RNA, the master regulator of XCI, though competitive binding to Xist regulatory regions.[130]

Some ASD is associated with clearly genetic conditions, like fragile X syndrome, but only around 2% of autistic people have fragile X.[84] Hypotheses from evolutionary psychiatry suggest that these genes persist because they are linked to human inventiveness, intelligence or systemising.[131][132]

Current research suggests that genes that increase susceptibility to ASD are ones that control protein synthesis in neuronal cells in response to cell needs, activity and adhesion of neuronal cells, synapse formation and remodeling, and excitatory to inhibitory neurotransmitter balance. Therefore, although up to 1,000 different genes are thought to increase the risk of ASD, all of them eventually affect normal neural development and connectivity between different functional areas of the brain in a similar manner that is characteristic of an ASD brain. Some of these genes are known to modulate production of the GABA neurotransmitter, the nervous system's main inhibitory neurotransmitter. These GABA-related genes are under-expressed in an ASD brain. On the other hand, genes controlling expression of glial and immune cells in the brain, e.g. astrocytes and microglia, respectively, are over-expressed, which correlates with increased number of glial and immune cells found in postmortem ASD brains. Some genes under investigation in ASD pathophysiology are those that affect the mTOR signaling pathway, which supports cell growth and survival.[133]

All these genetic variants contribute to the development of the autistic spectrum, but it cannot be guaranteed that they are determinants for the development.[134]

ASD may be under-diagnosed in women and girls due to an assumption that it is primarily a male condition,[135] but genetic phenomena such as imprinting and X linkage have the ability to raise the frequency and severity of conditions in males, and theories have been put forward for a genetic reason why males are diagnosed more often, such as the imprinted brain hypothesis and the extreme male brain theory.[136][137][138]

Several prenatal and perinatal complications have been reported as possible risk factors for autism. These risk factors include maternal gestational diabetes, maternal and paternal age over 30, bleeding during pregnancy after the first trimester, use of certain prescription medication (e.g. valproate) during pregnancy, and meconium in the amniotic fluid. While research is not conclusive on the relation of these factors to autism, each of these factors has been identified more frequently in children with autism, compared to their siblings who do not have autism, and other typically developing youth.[139] While it is unclear if any single factors during the prenatal phase affect the risk of autism,[140] complications during pregnancy may be a risk.[140]

There are also studies being done to test whether certain types of regressive autism have an autoimmune basis.[141]

Maternal nutrition and inflammation during preconception and pregnancy influences fetal neurodevelopment. Intrauterine growth restriction is associated with ASD, in both term and preterm infants.[142] Maternal inflammatory and autoimmune diseases may damage fetal tissues, aggravating a genetic problem or damaging the nervous system.[143]

Exposure to air pollution during child pregnancy, especially heavy metals and particulates, may increase the risk of autism.[144][145] Environmental factors that have been claimed without evidence to contribute to or exacerbate autism include certain foods, infectious diseases, solvents, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, vaccines,[146] and prenatal stress. Some, such as the MMR vaccine, have been completely disproven.[147][148][149][150]

Parents may first become aware of ASD symptoms in their child around the time of a routine vaccination. This has led to unsupported and disproven theories blaming vaccine "overload", the vaccine preservative thiomersal, or the MMR vaccine for causing autism spectrum disorder.[151] In 1998, British physician and academic Andrew Wakefield led a fraudulent, litigation-funded study that suggested that the MMR vaccine may cause autism.[152][153][154][155][156]

Two versions of the vaccine causation hypothesis were that autism results from brain damage caused by either the MMR vaccine itself, or by mercury used as a vaccine preservative.[157] No convincing scientific evidence supports these claims.[12] They are biologically implausible,[151] and further evidence continues to refute them, including the observation that the rate of autism continues to climb despite elimination of thimerosal from most routine vaccines given to children from birth to 6 years of age.[158][159][160][161][162]

A 2014 meta-analysis examined ten major studies on autism and vaccines involving 1.25 million children worldwide; it concluded that neither the vaccine preservative thimerosal (mercury), nor the MMR vaccine, which has never contained thimerosal,[163] lead to the development of ASDs.[164] Despite this, misplaced parental concern has led to lower rates of childhood immunizations, outbreaks of previously controlled childhood diseases in some countries, and the preventable deaths of several children.[165][166]

Several hypotheses have been presented that try to explain how and why autism develops by integrating known causes (genetic and environmental effects) and findings (neurobiological and somatic). Some are more comprehensive, such as the Pathogenetic Triad, which proposes and operationalizes three core features (an autistic personality, cognitive compensation, neuropathological burden) that interact to cause autism,[167] and the Intense World Theory, which explains autism through a hyper-active neurobiology that leads to an increased perception, attention, memory, and emotionality.[168] There are also simpler hypotheses that explain only individual parts of the neurobiology or phenotype of autism, such as mind-blindness (a decreased ability for theory of mind), the weak central coherence theory, or the extreme male brain and empathising–systemising theory.

Research exploring the evolutionary benefits of autism and associated genes has suggested that autistic people may have played a "unique role in technological spheres and understanding of natural systems" in the course of human development.[169][170] It has been suggested that it may have arisen as "a slight trade off for other traits that are seen as highly advantageous", providing "advantages in tool making and mechanical thinking", with speculation that the condition may "reveal itself to be the result of a balanced polymorphism, like sickle cell anemia, that is advantageous in a certain mixture of genes and disadvantageous in specific combinations".[171]

In 2011, a paper in Evolutionary Psychology proposed that autistic traits, including increased abilities for spatial intelligence, concentration and memory, could have been naturally selected to enable self-sufficient foraging in a more (although not completely) solitary environment, referred to as the "Solitary Forager Hypothesis".[172][173][174] A 2016 paper examines Asperger syndrome as "an alternative prosocial adaptive strategy" which may have developed as a result of the emergence of "collaborative morality" in the context of small-scale hunter-gathering, i.e. where "a positive social reputation for making a contribution to group wellbeing and survival" becomes more important than complex social understanding.[175]

Conversely, some multidisciplinary research suggests that recent human evolution may be a driving force in the rise of a number of medical conditions in recent human populations, including autism. Studies in evolutionary medicine indicate that as biological evolution becomes outpaced by cultural evolution, disorders linked to bodily dysfunction increase in prevalence due to a lack of contact with pathogens and negative environmental conditions that once widely affected ancestral populations. Because natural selection primarily favors reproduction over health and longevity, the lack of this impetus to adapt to certain harmful circumstances creates a tendency for genes in descendant populations to over-express themselves, which may cause a wide array of maladies, ranging from mental disorders to autoimmune diseases.[176]

Research indicates that autistic people are significantly more likely to be LGBT than the general population.[22] There is tentative evidence that gender dysphoria occurs more frequently in autistic people.[179][180] A 2021 anonymized online survey of 16- to 90-year-olds revealed that autistic males are more likely to identify as bisexual, while autistic females are more likely to identify as homosexual.[181]

People on the autism spectrum are significantly more likely to be non-theistic than members of the general population.[23]

• The most common medical condition occurring in people with ASDs is seizure disorder or epilepsy, which occurs in 11–39% of autistic people.[182] The risk varies with age, cognitive level, and type of language disorder.[183]
• Tuberous sclerosis, an autosomal dominant genetic condition in which non-malignant tumors grow in the brain and on other vital organs, is present in 1–4% of people with ASDs.[184]
• Intellectual disabilities are some of the most common comorbid disorders with ASDs. As diagnosis is increasingly being given to people with higher functioning autism, there is a tendency for the proportion with comorbid intellectual disability to decrease over time. In a 2019 study, it was estimated that approximately 30-40% of people diagnosed with ASD also have intellectual disability.[185] Recent research has suggested that autistic people with intellectual disability tend to have rarer, more harmful, genetic mutations than those found in people solely diagnosed with autism.[186] A number of genetic syndromes causing intellectual disability may also be comorbid with ASD, including fragile X, Down, Prader-Willi, Angelman, Williams syndrome,[187] branched-chain keto acid dehydrogenase kinase deficiency,[188][189] and SYNGAP1-related intellectual disability.[190][191]
• Learning disabilities are also highly comorbid in people with an ASD. Approximately 25–75% of people with an ASD also have some degree of a learning disability.[192]
• Various anxiety disorders tend to co-occur with ASDs, with overall comorbidity rates of 7–84%.[193] They 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.[194]
• Rates of comorbid depression in people with an ASD range from 4–58%.[195]
• The relationship between ASD and schizophrenia remains a controversial subject under continued investigation, and recent meta-analyses have examined genetic, environmental, infectious, and immune risk factors that may be shared between the two conditions.[196][197][198] Oxidative stress, DNA damage and DNA repair have been postulated to play a role in the aetiopathology of both ASD and schizophrenia.[199]
• Deficits in ASD are often linked to behavior problems, such as difficulties following directions, being cooperative, and doing things on other people's terms.[200] Symptoms similar to those of attention deficit hyperactivity disorder (ADHD) can be part of an ASD diagnosis.[201]
• Sensory processing disorder is also comorbid with ASD, with comorbidity rates of 42–88%.[202]
• Starting in adolescence, some people with Asperger syndrome (26% in one sample)[203] fall under the criteria for the similar condition schizoid personality disorder, which is characterized by a lack of interest in social relationships, a tendency towards a solitary or sheltered lifestyle, secretiveness, emotional coldness, detachment and apathy.[203][204][205] Asperger syndrome was traditionally called "schizoid disorder of childhood."
• Genetic disorders - about 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndromes.[206]
• Several metabolic defects, such as phenylketonuria, are associated with autistic symptoms.[207]
• Gastrointestinal problems are one of the most commonly co-occurring medical conditions in autistic people.[208] These are linked to greater social impairment, irritability, language impairments, mood changes, and behavior and sleep problems.[208][209][210] A 2015 review proposed that immune, gastrointestinal inflammation, malfunction of the autonomic nervous system, gut flora alterations, and food metabolites may cause brain neuroinflammation and dysfunction.[209] A 2016 review concludes that enteric nervous system abnormalities might play a role in neurological disorders such as autism. Neural connections and the immune system are a pathway that may allow diseases originated in the intestine to spread to the brain.[210]
• Sleep problems affect about two-thirds of people with ASD at some point in childhood. These most commonly include symptoms of insomnia, such as difficulty 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.[211]

Intensive, sustained special education or remedial education programs and behavior therapy early in life may help children acquire self-care, social, and job skills. Available approaches include applied behavior analysis, developmental models, structured teaching, speech and language therapy, cognitive behavioral therapy,[228] social skills therapy, and occupational therapy.[229] Among these approaches, interventions either treat autistic features comprehensively, or focus treatment on a specific area of deficit.[224] Generally, when educating those with autism, specific tactics may be used to effectively relay information to these people. Using as much social interaction as possible is key in targeting the inhibition autistic people experience concerning person-to-person contact. Additionally, research has shown that employing semantic groupings, which involves assigning words to typical conceptual categories, can be beneficial in fostering learning.[230]

There has been increasing attention to the development of evidence-based interventions for autistic young children. Three theoretical frameworks outlined for early childhood intervention include applied behavior analysis (ABA), the developmental social-pragmatic model (DSP) and cognitive behavioral therapy (CBT).[228][224] Although ABA therapy has a strong evidence base, particularly in regard to early intensive home-based therapy, ABA's effectiveness may be limited by diagnostic severity and IQ of the person affected by ASD.[231] The Journal of Clinical Child and Adolescent Psychology has published a paper deeming two early childhood interventions "well-established": individual comprehensive ABA, and focused teacher-implemented ABA combined with DSP.[224]

Another evidence-based intervention that has demonstrated efficacy is a parent training model, which teaches parents how to implement various ABA and DSP techniques themselves.[224] Various DSP programs have been developed to explicitly deliver intervention systems through at-home parent implementation.

In October 2015, the American Academy of Pediatrics (AAP) proposed new evidence-based recommendations for early interventions in ASD for children under 3.[232] These recommendations emphasize early involvement with both developmental and behavioral methods, support by and for parents and caregivers, and a focus on both the core and associated symptoms of ASD.[232] But a Cochrane review found no evidence that early intensive behavioral intervention (EIBI) is effective in reducing behavioral problems associated with autism in most autistic children, though it did improve IQ and language skills.[233] The Cochrane review acknowledged that this may be due to the low quality of studies available on EIBI and therefore providers should recommend EIBI based on their clinical judgment and the family's preferences.[233] No adverse effects of EIBI treatment were found.[233] A meta-analysis in that same database indicates that due to the degrees of severity in ASD, there is variable responses to differing early ABA interventions.[234]

ASD treatment generally focuses on behavioral and educational interventions to target its two core symptoms: social communication deficits and restricted, repetitive behaviors.[235] If symptoms continue after behavioral strategies have been implemented, some medications can be recommended to target specific symptoms or co-existing problems such as restricted and repetitive behaviors (RRBs), anxiety, depression, hyperactivity/inattention and sleep disturbance.[235] Melatonin, for example, can be used for sleep problems.[236]

Several parent-mediated behavioral therapies target social communication deficits in children with autism, but their efficacy in treating RRBs is uncertain.[237]

An autistic three-year-old points to fish in an aquarium, as part of an experiment on the effect of intensive shared-attention training on language development.[238]

Educational interventions often used include applied behavior analysis (ABA), developmental models, structured teaching, speech and language therapy and social skills therapy.[220] Among these approaches, interventions either treat autistic features comprehensively, or focalize treatment on a specific area of deficit.[222]

The quality of research for early intensive behavioral intervention (EIBI)—a treatment procedure incorporating over thirty hours per week of the structured type of ABA that is carried out with very young children—is low; more vigorous research designs with larger sample sizes are needed.[233] Two theoretical frameworks outlined for early childhood intervention include structured and naturalistic ABA interventions, and developmental social pragmatic models (DSP).[222] One interventional strategy utilizes a parent training model, which teaches parents how to implement various ABA and DSP techniques, allowing for parents to disseminate interventions themselves.[222] Various DSP programs have been developed to explicitly deliver intervention systems through at-home parent implementation. Despite the recent development of parent training models, these interventions have demonstrated effectiveness in numerous studies, being evaluated as a probable efficacious mode of treatment.[222] Early, intensive ABA therapy has demonstrated effectiveness in enhancing communication and adaptive functioning in preschool children;[220] it is also well-established for improving the intellectual performance of that age group.[220]

A 2018 Cochrane meta-analysis database concludes how some recent research is beginning to suggest that because of the heterology of ASD, there is two varying ABA teaching approaches to acquiring spoken language: children with more general expressive language delays respond sufficiently to the naturalistic approach, whereas children with receptive language delays require discrete trial training—a structured and intensive form of ABA.[234]

Similarly, a teacher-implemented intervention that utilizes a more naturalistic form of ABA combined with a developmental social pragmatic approach has been found to be beneficial in improving social-communication skills in young children, although there is less evidence in its treatment of global symptoms.[222] Neuropsychological reports are often poorly communicated to educators, resulting in a gap between what a report recommends and what education is provided.[239] The appropriateness of including children with varying severity of autism spectrum disorders in the general education population is a subject of current debate among educators and researchers.[240]

Medications may be used to treat ASD symptoms that interfere with integrating a child into home or school when behavioral treatment fails.[241] They may also be used for associated health problems, such as ADHD, anxiety, or if the person is hurting themself or aggressive with others,[241][242] but their routine prescription for ASD's core features is not recommended.[243] More than half of US children diagnosed with ASD are prescribed psychoactive drugs or anticonvulsants, with the most common drug classes being antidepressants, stimulants, and antipsychotics.[244][245] The atypical antipsychotic drugs risperidone and aripiprazole are FDA-approved for treating associated aggressive and self-injurious behaviors.[227][246] But their side effects must be weighed against their potential benefits, and autistic people may respond atypically.[227] Side effects may include weight gain, tiredness, drooling, and aggression.[227] Some emerging data show positive effects of aripiprazole and risperidone on restricted and repetitive behaviors (i.e., stimming; e.g., flapping, twisting, complex whole-body movements),[243] but due to the small sample size and different focus of these studies and the concerns about its side effects, antipsychotics are not recommended as primary treatment of RRBs.[247] SSRI antidepressants, such as fluoxetine and fluvoxamine, have been shown to be effective in reducing repetitive and ritualistic behaviors, while the stimulant medication methylphenidate is beneficial for some children with co-morbid inattentiveness or hyperactivity.[220] There is scant reliable research about the effectiveness or safety of drug treatments for adolescents and adults with ASD. No known medication relieves autism's core symptoms of social and communication impairments.[227]

A multitude of researched alternative therapies have also been implemented. Many have resulted in harm to autistic people.[229] A 2020 systematic review on adults with autism has provided emerging evidence for decreasing stress, anxiety, ruminating thoughts, anger, and aggression through mindfulness-based interventions for improving mental health.[248]

Although popularly used as an alternative treatment for autistic people, as of 2018 there is no good evidence to recommend a gluten- and casein-free diet as a standard treatment.[249][250][251] A 2018 review concluded that it may be a therapeutic option for specific groups of children with autism, such as those with known food intolerances or allergies, or with food intolerance markers. The authors analyzed the prospective trials conducted to date that studied the efficacy of the gluten- and casein-free diet in children with ASD (4 in total). All of them compared gluten- and casein-free diet versus normal diet with a control group (2 double-blind randomized controlled trials, 1 double-blind crossover trial, 1 single-blind trial). In two of the studies, whose duration was 12 and 24 months, a significant improvement in ASD symptoms (efficacy rate 50%) was identified. In the other two studies, whose duration was 3 months, no significant effect was observed.[249] The authors concluded that a longer duration of the diet may be necessary to achieve the improvement of the ASD symptoms.[249] Other problems documented in the trials carried out include transgressions of the diet, small sample size, the heterogeneity of the participants and the possibility of a placebo effect.[251][252][253] In the subset of people who have gluten sensitivity there is limited evidence that suggests that a gluten-free diet may improve some autistic behaviors.[254][255][256]

The preference that autistic children have for unconventional foods can lead to reduction in bone cortical thickness with this risk being greater in those on casein-free diets, as a consequence of the low intake of calcium and vitamin D; however, suboptimal bone development in ASD has also been associated with lack of exercise and gastrointestinal disorders.[257] In 2005, botched chelation therapy killed a five-year-old child with autism.[258][259] Chelation is not recommended for autistic people since the associated risks outweigh any potential benefits.[260] Another alternative medicine practice with no evidence is CEASE therapy, a pseudoscientific mixture of homeopathy, supplements, and "vaccine detoxing".[261]

Results of a systematic review on interventions to address health outcomes among autistic adults found emerging evidence to support mindfulness-based interventions for improving mental health. This includes decreasing stress, anxiety, ruminating thoughts, anger, and aggression.[262] An updated Cochrane review (2022) found evidence that music therapy likely improves social interactions, verbal communication, and nonverbal communication skills.[263] There has been early research on hyperbaric treatments in children with autism.[264] Studies on pet therapy have shown positive effects.[265]

While infection with rubella during pregnancy causes fewer than 1% of cases of autism,[266] vaccination against rubella can prevent many of those cases.[267]

Some autistic people, as well as a growing number of researchers,[13] have advocated a shift in attitudes toward the view that autism spectrum disorder is a difference, rather than a disease that must be treated or cured.[309][310] Critics have bemoaned the entrenchment of some of these groups' opinions.[311][312][313][314]

The neurodiversity movement and the autism rights movement are social movements within the context of disability rights, emphasizing the concept of neurodiversity, which describes the autism spectrum as a result of natural variations in the human brain rather than a disorder to be cured.[299][90] The autism rights movement advocates for including greater acceptance of autistic behaviors; therapies that focus on coping skills rather than imitating the behaviors of those without autism;[315] and the recognition of the autistic community as a minority group.[315][316]

Autism rights or neurodiversity advocates believe that the autism spectrum is genetic and should be accepted as a natural variation in the human genome.[299] These movements are not without detractors; a common argument against neurodiversity activists is that most of them have relatively low support needs, or are self-diagnosed, and do not represent the views of autistic people with higher support needs.[316][317][318] Jacquiline den Houting explores this critique, determining that the voices of low-support needs autistics are "some of the most influential within the neurodiversity movement, although admittedly these voices are a minority within the advocacy community"; she suggests this is in part a shortcoming of the wider neurotypical community, referencing non-speaking self-advocate Amy Sequenzia's writing.[319][320] Pier Jaarsma and Stellan Welin make the argument that only high-functioning autists should be included under the neurodiversity banner, as including low-functioning autists within this concept is deemed problematic, because their condition may rightfully be viewed as a disability.[321] The concept of neurodiversity is contentious in autism advocacy and research groups and has led to infighting.[322][323]

Over the years, multiple organizations have tried to capture the essence of autism in symbols. In 1963, the board for the National Autistic Society, led by Gerald Gasson, proposed the "puzzle piece" as a symbol for autism, because it fit their view of autism as a "puzzling condition".[324] In 1999, the Autism Society adopted the puzzle ribbon as the universal sign of autism awareness.[324] In 2004, neurodiversity advocates Amy and Gwen Nelson conjured the "rainbow infinity symbol". It was initially the logo for their website, Aspies for Freedom. Nowadays, the prismatic colors are often associated with the neurodiversity movement in general.[325] The autistic spectrum has also been symbolized by the infinity symbol itself.[326] In 2018, Julian Morgan wrote the article "Light It Up Gold", a response to Autism Speaks's "Light It Up Blue" campaign, launched in 2007.[327][328] Aurum is Latin for gold,[325] and gold has been used to symbolize autism, since both words start with "Au". Though a consensus for a flag to unite autism and neurodiversity has not yet been established, one has gained traction on Reddit.[329] The flag implements a gradient to represent the Pride Movement and incorporates a golden infinity symbol as its focal point.[330] While flags are symbols of solidarity, they may trigger negative associations, such as apparent rivalry among two or more flags.[331] For this reason, flags are sought that can be tailored to the personal preferences of any neurotype.[332][333]

• 
  Autism infinity symbol
• 
  Autistic pride flag
• 
  The puzzle piece symbol as used in the autism awareness ribbon used by Autism Speaks

Families who care for an autistic child face added stress from a number of different causes.[80][334] Parents may struggle to understand the diagnosis and to find appropriate care options. They often take a negative view of the diagnosis, and may struggle emotionally.[335] More than half of parents over age 50 are still living with their child, as about 85% of autistic people have difficulties living independently.[336] Some studies also find decreased earnings among parents who care for autistic children.[337][338] Siblings of children with ASD report greater admiration and less conflict with the affected sibling than siblings of unaffected children, like siblings of children with Down syndrome. But they reported lower levels of closeness and intimacy than siblings of children with Down syndrome; siblings of people with ASD have a greater risk of negative well-being and poorer sibling relationships as adults.[339]

• "Neurodevelopmental Disorders". Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR). Washington, DC: American Psychiatric Association. 18 March 2022. ISBN 9780890425770. LCCN 2021051782.
• "6A02 Autism spectrum disorder". International Classification of Diseases 11th Revision (ICD-11). World Health Organisation. February 2022 [adopted in 2019]. 6A02. Retrieved 14 May 2022.