Autism Spectrum Disorder

The specific cause in most cases of autism spectrum disorder remains elusive. However, it has been associated with congenital rubella syndrome, congenital cytomegalovirus, phenylketonuria and other inborn errors of metabolism, tuberous sclerosis complex, Down syndrome, and fragile X syndrome (1–4).

Strong evidence supports a genetic component, with heritability estimated at 83% (5). For parents of 1 child with autism spectrum disorder, risk of having a subsequent child with autism spectrum disorder is around 20% (6, 7). Male infant sex and >1 older affected sibling were significant predictors of familial recurrence. Siblings of female probands are significantly more likely to develop ASD than siblings of male probands. The concordance rate of autism is high in monozygotic twins. Research on families has suggested several potential target gene areas, including those related to neurotransmitter receptors (serotonin and gamma-aminobutyric acid [GABA]) (8, 9 ).

Differences in brain structure and function probably underlie much of the etiology of autism spectrum disorder. Differences have been identified in the cerebellum, amygdala, hippocampus, frontal cortex, and brain stem nuclei (10).

Research also suggests incidence of autism spectrum disorder increases with increasing prematurity (11).

Environmental causes have been suspected but are unproved.

There is compelling evidence that vaccinations do not cause autism (12), and the primary study that suggested this association was retracted by the journal that published it because its author falsified data. Multiple subsequent studies have disproved an association between MMR vaccine and autism. (See also Vaccine Hesitancy: Measles-Mumps-Rubella [MMR] Vaccine.)

One study has suggested phenotypic subtypes within the autism spectrum, possibly with differing genetic predispositions (13). These differ based on cognitive and behavioral symptoms, and are characterized and grouped as mixed ASD with developmental delay; social/behavioral; broadly affected; and moderate challenges.

Autism spectrum disorder may manifest during the first year of life, but, depending on severity of symptoms, diagnosis may not be clear until school age.

Two main features characterize autism spectrum disorder (1):

• Persistent deficits in social communication and interaction

• Restricted, repetitive patterns of behavior, interests, and/or activities

Both of these features must be present at a young age (although they may not be recognized at the time) and must be severe enough to significantly impair the child's ability to function at home, school, or in other environments. Manifestations must be more pronounced than expected for the child’s developmental level and adjusted for norms in different cultures.

Examples of deficits in social communication and interaction include

• Deficits in social and/or emotional reciprocity (eg, failure to initiate or respond to social interactions or conversation, no sharing of emotions)

• Deficits in nonverbal social communication (eg, difficulty interpreting others' body language, gestures, and expressions; diminished facial expressions and gestures and/or eye contact)

• Deficits in developing and maintaining relationships (eg, making friends, adjusting behavior to different situations)

The first manifestations noticed by parents may be delayed language development, lack of pointing at things from a distance after age 15 months, and lack of interest in parents' faces, making eye contact, or typical play.

Examples of restricted, repetitive patterns of behavior, interests, and/or activities include

• Stereotyped or repetitive movements or speech (eg, repeated hand flapping or finger flicking, repeating idiosyncratic phrases or echolalia, lining up toys)

• Inflexible adherence to routines and/or rituals (eg, having extreme distress with small changes in meals or clothing, having stereotyped greeting rituals)

• Highly restricted, abnormally intense, fixated interests (eg, preoccupation with vacuum cleaners)

• Extreme over- or underreaction to sensory input (eg, extreme aversion to specific smells, tastes, or textures; apparent indifference to pain or temperature)

Some stereotyped/repetitive movements and speech are referred to as self-stimulatory behavior or "stimming."

Some affected children injure themselves. Approximately 20% of affected children experience a documented loss of previously acquired skills (2).

All children with autism spectrum disorder have at least some difficulty with interaction, behavior, and communication; however, the severity of the problems varies widely.

One commonly held current theory holds that a fundamental problem in autism spectrum disorder is "mind blindness," the inability to imagine what another person might be thinking. This difficulty is thought to result in interaction abnormalities that, in turn, lead to abnormal language development. One of the earliest and most sensitive markers for autism spectrum disorder is a 15-month-old child’s inability to point communicatively at objects at a distance (3). It is theorized that the child cannot imagine that another person would understand what was being indicated; instead, the child indicates wants only by physically touching the desired object or using the adult’s hand as a tool. Research also suggests that differences in sensory processing underlie the social interaction and communication differences present in young children with autism spectrum disorder (4).

Comorbid conditions are common, particularly intellectual disability and learning disorders (5). Nonfocal neurologic findings include poorly coordinated gait and stereotyped motor movements. Seizures, which are reported to occur in 8 to 9% of individuals with autism, occur in 21 to 25% of individuals with both autism and intellectual disability (6).

• Clinical evaluation

• Sometimes genetic or metabolic testing

Diagnosis of autism spectrum disorder is made clinically based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR), and requires evidence of impairment of social interaction and communication and presence of ≥ 2 restricted, repetitive, stereotyped behaviors or interests (as described above under Symptoms and Signs of Autism Spectrum Disorder [1]). Although the manifestations of autism spectrum disorder can vary significantly in scope and severity, previous categorizations such as Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder are encompassed under autism spectrum disorder and are no longer distinguished.

Autism spectrum disorder is currently divided into severity levels based upon the degree of support required (2):

• Level 1: Requires some support (coaching in social and behavioral skills)

• Level 2: Requires substantial support (structured environment and activity, some assistance with daily living)

• Level 3: Requires very substantial support (intensive support throughout the day)

Screening tests include the Social Communication Questionnaire (3) for older children and the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F) (4). Universal screening for autism between the ages of 18 to 24 months is recommended by some organizations including the American Academy of Pediatrics, and guidelines support this screening schedule (5, 6).

Formal standard diagnostic tests such as the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) (7), based on criteria in the DSM-5-TR, are usually administered by psychologists or developmental-behavioral pediatricians. Another commonly used tool is the Childhood Autism Rating Scale–Second Edition (CARS2 [8]), which also has a version for testing individuals with higher measured intelligence levels. Children with autism spectrum disorder can be difficult to test; they often do better on performance items than verbal items in IQ tests and may show instances of age-appropriate performance despite cognitive limitation in most areas. Nonetheless, reliable diagnosis of autism spectrum disorder is becoming increasingly possible at younger ages. An IQ test administered by an experienced examiner often can provide a useful predictor of outcome.

In addition to standardized diagnostic tests, metabolic and genetic testing should be offered as indicated to help identify treatable or inherited disorders. Testing might include a chromosomal microarray, testing for fragile X syndrome when suggested by family history, for Rett syndrome in girls, for inherited disorders of metabolism when suspected, and further genetics evaluation (potentially including whole exome sequencing) when no etiology is found (1).

• Applied behavior analysis

• Speech and language therapy

• Sometimes physical and occupational therapy

• Pharmacotherapy

Treatment of autism spectrum disorder is usually multidisciplinary, and research shows measurable benefits from intensive, behaviorally based approaches that encourage interaction and meaningful communication (1). Psychologists and educators typically focus on behavioral analysis and then match behavioral management strategies to specific behavioral problems at home and at school. (See also the American Academy of Pediatrics' clinical report Identification, Evaluation, and Management of Children with Autism Spectrum Disorder, which was written in 2020 and reaffirmed in 2025.)

Applied behavior analysis (ABA) is an approach to therapy in which children are taught specific cognitive, social, or behavioral skills in a stepwise fashion. Small improvements are reinforced and progressively built upon to improve, change, or develop specific behaviors in children who have autism spectrum disorder. These behaviors include social skills, language and communication skills, reading, and academics as well as learned skills such as self-care (eg, showering, grooming), daily-living skills, punctuality, and job competence. This therapy is also used to help children minimize behaviors (eg, aggression) that may interfere with their progress. Applied behavior analysis therapy is tailored to meet the needs of each child and is typically designed and supervised by professionals certified in behavior analysis. In the United States, ABA may be available as part of an Individualized Educational Plan (IEP) through schools. The Developmental, Individual-differences, Relationship-based (DIR^®) model, also called Floortime, is another intensive behaviorally based approach. DIR® draws on the child's interests and preferred activities to help build social interaction skills and other skills. At present, there is less evidence to support DIR/Floortime than ABA, but both therapies can be effective (1–4).

Speech and language therapy should begin early (1), and use a range of media, including signing, picture exchange, and augmentative communication devices such as those that generate speech based on symbols children select on a tablet or other handheld device, as well as speech. Physical and occupational therapists plan and implement strategies to help affected children compensate for specific deficits in motor function, motor planning, and sensory processing.

Medications may help relieve certain symptoms, although they do not resolve the primary communication and social symptoms that define ASD. There is evidence that atypical antipsychotic medications (eg, risperidone, aripiprazole) help relieve behavioral problems, such as ritualistic, self-injurious, and aggressive behaviors (5). Other medications are sometimes used to control specific symptoms, including selective serotonin reuptake inhibitors (SSRIs) for ritualistic behaviors and anxiety, mood stabilizers (eg, valproic acid) for self-injury and outburst behaviors, and stimulants and other ADHD medications for inattention, impulsivity, and hyperactivity.

Dietary interventions, including some vitamin supplements and a gluten-free and casein-free diet, are not helpful enough to be recommended; however, many families choose to try them, leading to the need to monitor for dietary insufficiencies and excesses (1). Other complementary and investigational approaches to therapy (eg, facilitated communication, chelation therapy, auditory integration training, hyperbaric oxygen therapy) have not shown efficacy and can be dangerous.

In most patients, symptoms of ASD persist throughout life (1). The majority live with parents, family, or in group or institutional living situations through adulthood; one-quarter live in their own households. The overall prognosis is strongly influenced by how much usable language the child has acquired by elementary school age.

The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.

1. Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F)

2. American Academy of Pediatrics: Identification, Evaluation, and Management of Children With Autism Spectrum Disorder (2020)

3. Learning Disabilities Association of America (LDA)

4. Autism Society

5. Autism Speaks

6. National Autism Association