What are the causes of autism?

Causes of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is primarily caused by a complex interplay of genetic factors and environmental influences, with genetics playing the predominant role in most cases. 1

Genetic Factors

Genetic Evidence

• Strong genetic basis supported by multiple lines of epidemiologic evidence 1
• Heritability estimated at approximately 90% 1
• Twin studies show 70% concordance in monozygotic twins (increasing to 92% when considering broader autism phenotype) compared to only 3% in dizygotic twins 1, 2
• Recurrence risk in siblings ranges from 4-19%, much higher than general population prevalence 1
  • 7% if first affected child is female
  • 4% if first affected child is male
  • 25-35% if two or more children already affected 1

Specific Genetic Findings

• Multiple genes are involved rather than a single gene 1
• Evidence suggests interactions of at least 10 genes in autism causation 2
• Most consistently reported genetic linkages include:
  • Chromosome 15q11-13
  • Chromosome 7q22-31 (two loci with parent-of-origin effect)
  • Chromosomes 13q, 17q11, 2q, and 16p 1
• Genetic testing including chromosomal microarray analysis is clinically indicated for all suspected ASD cases 1

Environmental Factors

Environmental factors appear to contribute to ASD risk, particularly during prenatal and early postnatal development:

• Advanced maternal or paternal age 1
• Closer spacing of pregnancies 1
• Extremely premature birth (<26 weeks gestational age) 1
• Prenatal exposure to environmental chemicals including:
  • Air pollutants
  • Pesticides
  • Various chemicals in household products 1
• Prenatal infections such as rubella and cytomegalovirus 2
• Perinatal complications 2, 3

Gene-Environment Interactions

The current understanding suggests a model where:

1. Genetic susceptibility creates vulnerability
2. Environmental exposures during critical developmental periods trigger or amplify pathological processes
3. These interactions affect neurodevelopment, particularly synaptic function and brain connectivity 3

Debunked Theories

Several proposed causes have been thoroughly investigated and found not to be associated with autism:

• Vaccines: The preponderance of available data does not support a link between vaccines (including MMR) and autism 1, 2
• Mercury/thimerosal: No established causal relationship between mercury exposure and ASD 4

Neurobiological Mechanisms

The genetic and environmental factors ultimately affect brain development through several mechanisms:

• Disruption in synaptic transmission and plasticity 3
• Imbalance in excitatory/inhibitory pathways 3
• Abnormal brain growth patterns 1
• Functional magnetic resonance imaging shows differences in tasks involving social and affective judgments 1
• Structural MRI has shown overall brain size increase in autism 1

Clinical Implications

• Genetic testing is warranted for all suspected ASD cases, including:
  • Chromosomal microarray analysis
  • Fragile X testing (especially in males)
  • MECP2 sequencing in females or males with specific clinical features 1
• Genetic counseling is important for families regarding recurrence risk
• Early identification and intervention remain critical for improving outcomes

Common Pitfalls to Avoid

1. Attributing autism to a single cause rather than recognizing its complex, multifactorial etiology
2. Pursuing unproven "treatments" based on debunked causal theories
3. Overlooking the need for genetic testing and counseling
4. Failing to recognize that the increased prevalence of ASD (1 in 59 as of 2014) likely reflects improved awareness, broader diagnostic criteria, and better detection rather than new environmental influences 1, 2

The understanding of autism etiology continues to evolve, with ongoing research focusing on identifying specific genetic and environmental risk factors and their interactions to develop better prevention strategies and treatments.