Causes of Autism Spectrum Disorder (ASD)
Autism Spectrum Disorder (ASD) is primarily caused by genetic factors, with heritability estimated at approximately 90%, though environmental factors and gene-environment interactions also contribute to its development. 1
Genetic Factors as Primary Cause
Genetic factors play the dominant role in ASD etiology:
- Twin studies show 70% concordance in monozygotic twins (90% when using broader phenotypic definitions), compared to only 3% in dizygotic twins 2
- Sibling recurrence risk is significantly higher than general population prevalence:
- 4-19% overall recurrence risk for siblings
- 7% if the first affected child is female
- 4% if the first affected child is male
- 25-35% if two or more children are already affected 2
- The calculated heritability (proportion of phenotypic variance explained by genetics) is around 90% 2
Genetic Linkages and Patterns
- Evidence of linkage has been found across most autosomes, indicating significant genetic heterogeneity 2
- The most consistently reported linkages involve chromosomal locations:
- 15q11-13
- 7q 22-31 (two loci with parent-of-origin effect)
- 13q
- 17q11 (male-specific locus)
- 2q
- 16p 2
- Males are affected 3-4 times more frequently than females, suggesting possible X-linked genetic contributions, though X-chromosome genes account for only a small portion of the overall genetic contribution 2, 1
Environmental Risk Factors
Several environmental factors have been identified that may contribute to ASD risk:
- Parental age: Advanced maternal or paternal age increases risk 1
- Pregnancy spacing: Closer spacing between pregnancies increases risk 1
- Premature birth: Extremely premature birth (<26 weeks gestational age) increases risk 1
- Prenatal chemical exposures: Air pollutants, pesticides, and various household chemicals may contribute to risk 1
- Metabolic conditions: Maternal diabetes during pregnancy increases risk 3
- Medication exposure: Valproate exposure during pregnancy significantly increases risk 3
- Immune activation: Maternal immune activation during pregnancy may contribute to risk 3
What Does NOT Cause Autism
It's important to note what the evidence shows does NOT cause autism:
- Vaccines: The preponderance of available data does not support any link between vaccines (including MMR) and autism 1
- Mercury exposure: No established causal relationship between mercury exposure and ASD has been found 1
Neurobiological Findings in ASD
Several neurobiological differences have been observed in individuals with ASD:
- Aberrations in white matter tract development 1
- Elevated peripheral levels of serotonin 1
- Possible imbalance of excitation and inhibition in neural systems 1
- Abnormal brain growth patterns 1
- Differences in brain activity during tasks involving social and affective judgments 1
- Overall brain size increase 1
Comorbidities and Associated Conditions
Individuals with ASD often have comorbid conditions that may complicate diagnosis and treatment:
- ADHD, GI disorders, and disrupted sleep affect more than half of individuals with ASD 1
- Epilepsy occurs in 5-46% of children with ASD 1
- Motor impairments including delayed motor milestones, apraxia, hypotonia, and malcoordination 1
- Sleep disturbances (53-78% of individuals) 1
- Anxiety disorders 1
- Depression (20% vs 7% in general population) 4
Clinical Implications
Understanding the multifactorial etiology of ASD has important implications:
- Genetic counseling is essential for families regarding recurrence risk 1
- Early identification and intervention are critical for improving outcomes 1
- Recognition of heterogeneity in ASD suggests that specific subsets of individuals may respond differently to various interventions 1
- Medical disorders may affect clinical presentation and response to interventions 1
The increasing prevalence of ASD (from 1.1% in 2008 to 2.3% in 2018 in the US) is likely associated with changes in diagnostic criteria, improved screening tools, and increased public awareness rather than representing a true "epidemic" 2, 4.