Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a pervasive developmental disorder consisting of disturbances in social relatedness and restricted interests and activities, with onset in early childhood. The reported prevalence of ASD varies based on study methodology and population; the Centers for Disease Control and Prevention (CDC) estimates that the prevalence of ASD in 2020 grew to 1 in 36 eight-year-old children and was four times as prevalent among boys than among girls. In earlier versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), disturbances in language and play were required for a diagnosis of autism; although these disturbances are often present, they are no longer required in the DSM-5-TR diagnostic criteria (see below). Additionally, autism and Asperger syndrome were separate diagnostic entities in earlier editions of DSM, while in the DSM-5, autism spectrum disorder (ASD) and Asperger syndrome are combined into one diagnostic category.

[Image] — **Prevalence of Autism Spectrum Disorder in 8-year-olds (2020)**

Etiology

Evidence suggests both neurobiologic and genetic contributions to the development of ASD. As many as 20% to 25% of individuals with ASD have seizure disorders and electroencephalogram (EEG) abnormalities. Some studies have demonstrated anatomical and neurotransmitter differences between patients with ASD and neurotypical individuals, but these differences are not yet clinically useful. Siblings and twins have higher ASD concordance rates. Closer spacing of pregnancies, advanced parental age, and extremely premature birth have also been linked with ASD. Despite much discussion in the public domain, multiple scientific studies have not demonstrated a link between ASD and vaccines.

Evaluation and Diagnosis

Depending on the severity of symptoms and the level of impairment, patients with autism present for initial evaluation at different developmental stages. In children, it is important to make a diagnosis of autism as early as possible so that they can benefit from available therapies, additional resources, and school support. The American Academy of Pediatrics (AAP) recommends that all children be screened for ASD at ages 18 and 24 months using a validated tool.

ASD has specific identifiers to categorize the presence of intellectual impairment, degree of support required, presence of catatonia, and/or if it is associated with known genetic, environmental, medical, neurodevelopmental, or behavioral factors. This specificity is important given the broad range of manifestations and to help guide treatment.

Summary of DSM-5-TR-Diagnostic Criteria for Autism Spectrum Disorder
The individual exhibits deficits in social communication and social interaction across multiple contexts, as manifested by all of the following, currently or by history (examples are illustrative, not exhaustive; see text): deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers The individual exhibits restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive; see text): stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases) insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food every day) highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests) hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement) Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities or may be masked by learned strategies in later life). Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. These disturbances are not better explained by intellectual developmental disorder (intellectual disability) or global developmental delay. Intellectual developmental disorder and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual developmental disorder, social communication should be below that expected for general developmental level.

Summary of DSM-5-TR-Diagnostic Criteria for Autism Spectrum Disorder

The individual exhibits deficits in social communication and social interaction across multiple contexts, as manifested by all of the following, currently or by history (examples are illustrative, not exhaustive; see text):
- deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions
- deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication
- deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers
The individual exhibits restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive; see text):
- stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases)
- insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food every day)
- highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests)
- hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement)
Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities or may be masked by learned strategies in later life).
Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
These disturbances are not better explained by intellectual developmental disorder (intellectual disability) or global developmental delay. Intellectual developmental disorder and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual developmental disorder, social communication should be below that expected for general developmental level.

Screening

Standard pediatric development screens include questions about core symptoms of ASD (social relatedness, repetitive or unusual behaviors). The MCHAT-R is a screening tool that signals when further evaluation is indicated. Whether raised by history or screening, concern for the possibility of autism requires a more comprehensive diagnostic assessment or referral for further evaluation.

Neuropsychological testing: The Autism Diagnostic Observation Schedule (ADOS-2) is the gold standard for the diagnosis of ASD. ADOS is a semistructured assessment of communication, social interaction, and play administered by a psychologist (PhD) when there is clinical concern for autism. Although this testing is quite comprehensive and time-consuming, the diagnosis remains a clinical one (and thus a patient can have autism with a negative or inconclusive ADOS).

On general neuropsychological testing, children with autism can display impairments in executive functioning, weak central coherence (integrating information into meaningful wholes), and deficits in theory-of-mind tasks (taking the perspective of another person).

Differential Diagnosis

Other conditions that may be confused with ASD include the following:

Developmental disorders (including language disorders): Because impaired language development can affect socialization, developmental disorders are challenging to differentiate from ASD. One diagnostic clue is that toddlers without autism will point for interest (joint attention) and use conventional gestures. Children with ASD are more likely to show impaired nonverbal behaviors to regulate social interaction.
Sensory impairments (especially deafness): All patients should have their hearing tested to ensure adequate hearing for speech.
Reactive attachment disorder: Patients with reactive attachment disorder can demonstrate inappropriate social responsibility, although this behavior usually improves substantially with adequate caretaking.
Obsessive compulsive disorder (OCD): Repetitive behaviors can occur in both OCD and ASD, but OCD is not typically associated with other core features of ASD (e.g., social impairments).
Intellectual disability: Patients with severe intellectual disability may have deficits in communication or social impairment, but those with mild or moderate intellectual disability do not have autism if they are still sociable and interested in social interactions.
Anxiety disorders (including selective mutism): Certain components of anxiety disorders, such as excessive worry, need for reassurance, inability to relax, and self-consciousness, are also seen in ASD.
Childhood-onset schizophrenia: Negative symptoms may mimic ASD; however, florid delusions and hallucinations are rarely seen in ASD.
Social (pragmatic) communication disorder: When considering the potential diagnosis of ASD, special consideration should be given to social (pragmatic) communication disorder. Patients with either diagnosis can present with marked deficits in social communication from early childhood, but those with social (pragmatic) communication disorder lack the symptoms of restricted, repetitive patterns of behavior, interests, or activities consistent with the diagnosis of ASD.

Comorbidities: In the setting of impaired communication, comorbidities can be challenging to identify. Most studies indicate that ASD is associated with higher rates of anxiety and attentional disorders. Patients with higher IQs may have a nonverbal learning disability. Bullying is common in patients with ASD, and some demonstrate overt signs of clinical depression related to bullying.

Evaluation

When ASD is suspected or diagnosed in a child, a comprehensive assessment, typically multidisciplinary in nature, is required. All children with ASD should undergo the following evaluations:

physical examination
hearing screen
Wood lamp examination looking for signs of tuberous sclerosis
genetic testing: medical geneticists recommend chromosomal microarray for initial evaluation of children with development disabilities, ASD, or both. In a community sample, microarray yielded diagnostic information in 24% of children with ASD.
psychological assessment: including measurement of cognitive ability and adaptive skills
communication assessment: usually performed by a speech therapist
occupational and physical therapy evaluations: for sensory or motor difficulties
neurologic consultation, neuroimaging, or EEG: may be helpful if there is clinical concern

Unusual clinical features may prompt further evaluations, including:

infectious (concern for encephalitis or meningitis)
endocrinologic (concern for hypothyroidism)
metabolic (concern for homocystinuria)
traumatic (concern for head injury)
toxic (concern for fetal alcohol syndrome)

Management

Nonpharmacologic Treatment:

Intensive behavioral therapy: A groundbreaking study published in 1987 showed that intensive behavioral therapy was associated with increased educational attainment and IQ in children with ASD. Structured educational and behavioral interventions have been shown to be effective in children with ASD and are ideal when initiated early; hence, the imperative to identify and diagnose children as young as possible.
Applied behavioral analysis (ABA): ABA can be effective when applied to academic tasks, adaptive living skills, communication and social skills, and vocational skills. Such treatments are often offered, at least in part, by the local school district.
Speech and language therapy: Speech pathologists can help children with ASD learn to communicate or to use alternative communication modalities when needed.
Early intervention: Prior to age 3 years, children should be enrolled in an early intervention program. After age 3 years, an intensive individualized education program (IEP) administered through the public school system is indicated to ensure that children have access to all appropriate services over time.

Parents should be directed to the multiple organizations and resources available for families with children who are diagnosed with ASD.

Pharmacologic Management: Medications for specific targeted symptoms or comorbidities may be prescribed in children with ASD.

Risperidone and aripiprazole are approved by the FDA for the treatment of irritability associated with ASD. Evidence indicates that for serious behavior disturbance associated with ASD, medication management combined with parent training is more effective than medication alone.
Psychotropic medications or other classes (e.g., selective serotonin-reuptake inhibitors) are prescribed to treat comorbid anxiety or depressive illnesses.

Prognosis

Predictors of outcome for youth diagnosed with ASD include presence of communicative speech by 5 years of age and overall cognitive ability. Earlier intervention can help facilitate better outcomes.

When to Refer: