Psychiatry

Autism Spectrum Disorder (ASD)

Background

1. Definition
   • Developmental disability that can cause significant social, communication and behavioral challenges
2. General Information
   • ASD encompasses a spectrum of neurodevelopmental disabilities
   • Characterized by repetitive behavior, interests, activities and problems in social interactions
   • 5 major subtypes of ASD
     • Asperger's syndrome
       • Term no longer used
       • Reclassified as level 1 ASD
       • Term is used informally
     • Rett Syndrome
     • Childhood Disintegrative Disorder (CDD)
       • AKA Heller's syndrome or disintegrative psychosis
     • Autistic disorder
       • Described as "classic autistic disorder"
       • AKA Kanner's syndrome
     • Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)
       • Mild-type of autism that presents a range of symptoms
       • Most commonly social and language development challenges
       • Sometimes referred to as "subthreshold autism"
         • Term used to describe an individual with some but not all symptoms of autism
3. Epidemiology
   • Incidence/Prevalence
     • Prevalence is reported to be 1 in 68
     • CDD subtype is uncommon with an estimated prevalence of 1-2 cases/100,000
       • 60x less common than autistic disorder subtype
     • International prevalence estimate is 0.76% (WHO)
       • Accounts for only 16% of the global child population
   • Morbidity/Mortality
     • Dependent on IQ
       • Higher IQ individuals have better outcomes
     • Increased incidence of congenital anomalies

Pathophysiology

1. Pathogenesis
   • No clear pathology of ASD
   • Several genes have been implicated in the pathogenesis of ASD, most have involvement with neuronal synaptogenesis
   • Dysregulation of genes involved in the signal transduction mechanism of synapse formation
2. Etiology/Risk Factors
   • Unknown etiology
   • Onset variable
   • CDD (subtype of ASD) is assoc/ w/ following diseases
     • Subacute sclerosis panencephalitis
     • Tuberous sclerosis
     • Leukodystrophy
     • Lipid storage diseases
   • Sibling w/ ASD
   • Genetic/chromosomal conditions
     • Fragile X syndrome
     • Tuberous sclerosis
   • Complications at birth
   • Born to elderly parents

Diagnostics

1. History/Symptoms
   • Problems w/ social communication and interaction
   • Restricted, repetitive patterns of behavior, interests, or activities
   • Abnormal ways of learning, moving or paying attention
   • Symptoms must be present in early developmental period
     • May not manifest until social demands exceed limited capacities or
     • May be masked by learned strategies
2. Physical Examination/Signs
   • Normal development up to age at least 2 years
     • Presence of normal age-appropriate milestones are achieved in the areas of
       • Communication
       • Social relationships
       • Play
       • Adaptive behavior
     • Definite loss of previously acquired skills at the onset of the disorder
     • Diagnosis requires significant loss of skills (and not just a failure to use them in certain situations) in at least 2 of the following areas
       • Expressive or receptive language
       • Play
       • Social skills or adaptive behavior
       • Bowel or bladder control
       • Motor skills
3. Diagnostic Testing
   • Laboratory Evaluation
     • CBC
     • Urea and electrolytes/glucose
     • LFTs
     • TFTs
     • Heavy metal levels
     • HIV testing
     • Urine screening
       • Aminoaciduria
   • Others
     • EEG
     • DSM V Criteria
       • Deficits in social interaction and communication
       • Restricted interests, repetitive behavior and activities
       • These symptoms impair everyday functioning
4. Diagnostic Imaging
   • Neuroimaging
     • MRI
     • CT scan

Differential Diagnosis

1. Aminoaciduria
2. Brain tumor
3. Childhood schizophrenia
4. Creutz-Jakob disease/new variant CJD
5. Heavy metal poisoning
   • Mercury
   • Lead
6. HIV infection Hypothyroidism
7. Organophosphate exposure
8. Other rare conditions
   • Glycogen storage disorders
9. Seizure disorder (atypical)
10. Subacute sclerosing panencephalitis
11. Tuberous sclerosis

Treatment/Management

1. Basics
   • Bulk of treatment plan is behavior-based and highly structured
   • Parents should be educated on disorder so that they can follow child's treatment at home
     • Overall are heavily involved in treatment plan
   • Goals
     • Improve quality of life
     • Promote child's independence
     • Maximize function
   • Therapy
     • Speech
     • Social skills development
     • Occupational
     • Sensory integration
   • CDD
     • Behavior therapy
       • Re-learn self-care, language and social skills
       • Integrates speech therapists, physical therapists, psychologists and occupational therapists
     • Environment therapy
       • Sensory enrichment applies augmentation of the sensory experience to improve symptoms
     • Medications
2. Pharmacologic
   • No drug available to cure disease
   • FDA-approved drugs for ASD include risperidone and aripiprazole
     • Risperidone (Risperdal) work to block dopamine and serotonin
       • Higher levels of DA and 5-HT are assoc/ w/ happier moods but overproduction can cause psychotic, manic or aggressive behaviors
     • Aripiprazole
       • Partial agonist at the D2, D3 and 5-HT1A receptors
       • Also functions at 5-HT2A receptor
       • Acts as a functional antagonist in areas of high dopamine, such as mesolimbic pxy, while remaining inactive in areas with normal dopamine (e.g., nigrostriatal and tuberoinfundibular pxy)
   • Antipsychotics
     • Repetitive behavior patterns
     • Aggression
   • SSRIs, stimulants and other antipsychotics
     • Used to control problematic behavior, particularly aggression
   • Anticonvulsants
     • Seizure treatment
   • Corticosteroids
     • Seem to improve language, motor skills and behavior in CDD
3. Complications
   • Epilepsy
     • SSRIs and neuroleptics decrease seizure threshold (use w/ caution)
   • Normal life expectancy but with the complication of epilepsy
     • ASD mortality is 2x that of general population

Follow-Up

1. AAP guidelines recommended developmental surveillance at 9, 15, and 30 months of age
   • Autism specific screening at 18 months and again at 24 or 30 months
2. Requires routine follow-up and close monitoring

Prognosis

1. CDD prognosis is very poor compared w/ other subtypes of ASD
   • Most patients w/ CDD remain dependent on full-time caregivers or are institutionalized
2. Many co-occurring conditions are seen w/ ASD, including but not limited to
   • Anxiety
   • ADHD
   • OCD
   • Other mood disorders or disruptive behavior disorders

Prevention

1. No prevention or cure
2. Early diagnosis and early intensive management will produce most favorable outcome in all areas of disease spectrum
   • Screening tests should be performed during child's development if there any concerns for autism or other PDD
   • Commonly performed at 18-24 months during well-baby visits

References

1. Autism Spectrum Disorder. StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK525976/. [Accessed February 2024]
2. Centers for Disease Control and Prevention (CDC). Autism Spectrum Disorder (ASD). Available at: https://www.cdc.gov/ncbddd/autism/index.html. [Accessed February 2024]
3. Hodges H, Fealko C, Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. Feb 2020;9(Suppl 1):S55-S65
4. Ousley O, Cermak T. Autism Spectrum Disorder: Defining Dimensions and Subgroups. Curr Dev Disord Rep. Mar 1, 2014;1(1):20-28
5. Samsam M, Ahangari R, Naser SA. Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance. World J Gastroenterol. Aug 7, 2014;20(29):9942-51

Contributor(s)

1. Singh, Ajaydeep, MD
2. Ausi, Michael, MD, MPH

Updated/Reviewed: February 2024