Autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairment in social interaction and communication and restricted stereotyped patterns of behavior, interests, and activities. Although onset occurs in early childhood, features of ASD may not become fully apparent until later, when social demands exceed abilities. The etiology of ASD is complex and multifactorial; genetic and environmental factors likely play a role. Clinical features of ASD may be noted by parents and/or caregivers, or detected during screening for autism spectrum disorder. Diagnosis is clinical and based upon the DSM-5 diagnostic criteria for ASD; additional assessment for conditions associated with autism is recommended. Multimodal management should be initiated early and is typically carried out by a specialist (e.g., developmental pediatrician, child psychologist), a multidisciplinary team (e.g., psychiatrist, social worker, speech and language therapist), and/or publicly funded services (i.e., early intervention services or school services). Treatment targets impairments in communication and social interaction, as well as repetitive behaviors through behavioral, developmental, and educational interventions. Pharmacological treatment can be considered for specific problematic behaviors (e.g., atypical antipsychotics for irritability and aggression) and comorbid conditions (e.g., ADHD, anxiety).

• Prevalence: 32/1000 ^[1][2]
• Sex: ♂ > ♀ (3.4:1) ^[1]
• Age: Symptoms typically manifest before 2–3 years of age. ^[3]

Epidemiological data refers to the US, unless otherwise specified.

The etiology of autism spectrum disorder is complex and multifactorial. Contributing factors include the following: ^[2][4]

• Genetics
  • Strong genetic component
  • Many genes are associated with ASD.
• Environmental factors: Prenatal exposures (e.g., medications, infections) increase the risk of ASD, but no specific causes have been identified.

There is no link between autism and vaccines or their ingredients. ^[5][6]

Core features of ASD ^[2][4][7]

• Persistent impairment in communication and social interaction, e.g.:
  • Inability to initiate or participate in social interactions and conversational back-and-forth
  • Difficulty sharing thoughts or feelings with others
  • Poor eye contact
  • Limited use and understanding of nonverbal communication
  • Difficulty adjusting behavior to social situations
  • Lack of interest in peers or sharing in imaginative play
• Restricted, stereotyped patterns of behavior, interests, and activities
  • Repetitive movements or sounds, e.g.:
    • Hand flapping
    • Echolalia
  • Rigidity in routines, e.g.:
    • Distress at times of transition
    • Restrictive or repetitive eating patterns
  • Specific and abnormally focused interests (e.g., on atypical items)
  • Sensory abnormalities, e.g.:
    • Reduced or enhanced responses to sounds or pain
    • Excessive touching/smelling

Additional features ^[2][4]

• Language impairment, e.g.:
  • Delayed speech development
  • Regression in language skills
• Behavioral challenges (e.g., aggression, self-harm)
• Delays in achieving developmental milestones ^[8]
  • By 9 months: responding to name or showing facial expression
  • By 12 months: engaging in interactive games (e.g., pat-a-cake) or waving goodbye
  • By 15 months: sharing interests with other individuals (e.g., pointing to desired objects)
  • By 18 months: protodeclarative pointing
• Larger head circumference in toddlers ^[2]

Conditions associated with ASD ^[2][4][7]

• Epilepsy
• Other neurodevelopmental disorders, e.g.:
  • Intellectual disability
  • Language disorder
  • ADHD
• Psychiatric disorders, e.g.:
  • Mood disorders
  • Anxiety disorders
  • Obsessive-compulsive disorder
  • Catatonia
• Genetic disorders, e.g.:
  • Tuberous sclerosis
  • Fragile X syndrome
  • Rett syndrome
• Gastrointestinal disorders (e.g., constipation) and eating disorders (e.g., pica)
• Sleep disorders

ASD is associated with hearing and vision impairment, which sometimes manifest with similar features to the condition. ^[2][4]

The following screening recommendations are from the American Academy of Pediatrics (AAP). ^[2][9]

• Routine developmental screening: Assess for clinical features of ASD at 9, 18, and 30 months of age.
• Autism-specific screening ^[4]
  • Indications: all children at 18 and 24 months of age
  • Modality: a validated tool (e.g., Modified Checklist for Autism in Toddlers, Revised with Follow-up)
• Follow-up of abnormal screening: Refer patients to both of the following.
  • Diagnostic evaluation by a specialist (e.g., developmental pediatrician, child psychologist)
  • Early intervention or school services (see “Management of ASD”)

General principles ^[2][3]

• ASD is a clinical diagnosis typically made by a specialist, using the DSM-5 diagnostic criteria for ASD. ^[4][7]
• ASD severity is assessed based on functional impairment and support needs. ^[7]
• Additional testing should be performed as indicated to:
  • Identify conditions associated with ASD
  • Exclude alternative diagnoses

Do not delay referral for services while awaiting diagnostic confirmation for ASD. ^[2]

DSM-5 diagnostic criteria for ASD ^[7]

Diagnosis of ASD is confirmed in patients who meet all of the following criteria. See “Core features of ASD” for examples of specific manifestations.

• Persistent impairments in communication and social interaction in all of the following areas:
  • Social-emotional reciprocity
  • Nonverbal communication
  • Interpersonal relationships
• Repetitive and restricted interests, activities, and behavior in ≥ 2 of the following areas:
  • Repetitive and/or stereotyped movements
  • Insistence on sameness, rigid adherence to routines and behavior patterns
  • Abnormally focused interests
  • Sensory abnormalities
• Onset in early childhood
  • Features of ASD may not become fully apparent until later, when social demands exceed abilities.
  • Affected individuals may develop strategies that mask symptoms later in life.
• Symptoms cause functional impairment and are not due to alternative diagnoses.

Assessment for conditions associated with ASD ^[2][3]

Assessment is generally performed by a multidisciplinary team.

• Developmental evaluation
  • Cognitive and language testing
  • Gross and fine motor assessment
• Sensory evaluation
  • Assessment for hearing loss
  • Vision testing
• Genetic evaluation
  • Offer all patients referral to genetics to assess for hereditary causes of ASD.
  • Testing may include
    • Chromosomal microarray analysis
    • Fragile X syndrome testing
    • Testing for any suspected genetic syndrome (e.g., tuberous sclerosis)

Routine EEG and metabolic testing are not recommended and should only be performed if an underlying pathology is suspected. ^[2]

• Other causes of impaired social interaction (see “Differential diagnoses of impaired social interaction”)
• Other neurodevelopmental disorders (e.g., intellectual disability, stereotypic movement disorder)
• Other psychiatric disorders (e.g., anxiety disorders, obsessive-compulsive disorder)

The differential diagnoses listed here are not exhaustive.

The goals of management are to improve the core features of ASD, increase functional independence, minimize problematic behaviors, and treat associated conditions. ^[2]

General principles ^[2][3]

• Refer patients for multimodal management as early as possible. ^[14]
• Publicly funded programs can address developmental concerns while awaiting formal diagnostic confirmation.
  • < 3 years of age: early intervention services
  • ≥ 3 years of age: school services
• Treatment is individualized based on the patient's age, strengths, and needs and should include:
  • Early initiation of behavioral interventions ^[4]
  • Nonpharmacological and pharmacological treatment as needed for
    • Developmental delays
    • Specific behavioral concerns
    • Conditions associated with ASD
• Coordinate ongoing care and family support for patients and caregivers.

Services for management of ASD should be integrated across the child's home and educational settings. ^[2]

Behavioral interventions ^[2][4]

• Applied behavioral analysis (ABA) (e.g., discrete trial training, pivotal response training)
  • Uses positive reinforcement to teach new social and communication skills and minimize functional impairment
  • Can be highly structured or naturalistic (implemented in the context of the child's daily activities)
• Developmental approaches (e.g., Developmental Individual Differences and Relationship-based/Floortime model) ^[4]
  • Teach communication through social interaction.
  • Promote skill development (e.g., joint attention, symbolic play, social skills) and prevent aggressive and/or unsafe behaviors.
• Focused interventions address specific behaviors or build a single skill (e.g., social skills training) ^[4]

Early initiation of behavioral interventions greatly improves outcomes. ^[4]

Additional nonpharmacological interventions

• Speech-language therapy: for delayed language
• Occupational and/or physical therapy: for impaired fine and gross motor skills
• Cognitive behavioral therapy (CBT): for
  • Anxiety and depression ^[2][4]
  • Sleep disturbances ^[15]

Pharmacological treatment ^[2][4][16]

• Specific problematic behaviors
  • Irritability, disruptive, and/or repetitive stereotyped behavior: atypical antipsychotics (i.e., aripiprazole or risperidone) ^[2][17]
  • Behavioral rigidity: antiepileptics (e.g., divalproex sodium, valproic acid) ^[2]
• Comorbid conditions
  • ADHD: methylphenidate, atomoxetine, guanfacine
  • Anxiety and/or depression: SSRIs
  • Sleep disturbances: melatonin
  • Epilepsy: antiepileptic drugs

Risperidone and aripiprazole are the only FDA-approved drugs for controlling irritability in patients with ASD. ^[2]

• ASD is typically a lifelong condition that persists into adulthood. ^[2][4]
  • Symptoms may evolve.
  • Adolescents can experience social exclusion due to difficulty communicating with peers.
  • Adults with ASD are less likely to work and live independently.
• Prognosis varies, ranging from significant functional limitations to the development of exceptional skills in certain areas (e.g., in art or music). ^[4]
• Factors associated with worse prognosis include: ^[2][3]
  • Severe core symptoms
  • Intellectual impairment
  • Poor or absent language development
  • Late initiation of treatment
• Up to 30% of individuals with ASD never develop the ability to speak. ^[2]