Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterised by difficulties in social interaction, communication, and restricted or repetitive behaviours. The exact causes of autism remain unclear, but extensive research points to a combination of genetic and environmental risk factors that influence early brain development. In addition, known triggers of autism are communicated by the mother’s of autistic children, the most common being vaccines.
Genetic Factors in Autism
Whilst twin and family studies have consistently shown that autism has a strong genetic component, it is clearly influenced by environmental factors. A meta-analysis of twin studies estimated the heritability of ASD to be between 64% and 91%, indicating that genetic differences account for a substantial proportion of the likelihood of developing autism. Siblings of individuals with ASD have a 10-20 times higher risk of also being diagnosed compared to the general population .
While ASD is highly heritable, its genetic architecture is complex, involving a combination of rare and common genetic variants [2,3]. Rare mutations, including copy number variants (CNVs) and single nucleotide variants (SNVs), are found in 10-30% of individuals with ASD and often have a large effect size . Common variants, such as single nucleotide polymorphisms (SNPs), individually have small effects but cumulatively can contribute to a significant proportion of ASD risk [2,3]. Genetic studies have implicated hundreds of genes in ASD, many of which are involved in key processes like synaptic function, transcriptional regulation, and chromatin remodelling [2,3]. However, translating these genetic findings into clinical practice remains challenging due to the heterogeneity of ASD genetics and the variable expressivity and penetrance of identified variants .
Environmental Factors
While genes play a major role, environmental factors also contribute to the development of ASD, likely through complex interactions with genetic susceptibility. Several prenatal and perinatal exposures have been associated with increased autism risk, including parental age, air pollution, maternal infections and immune activation, maternal metabolic conditions, pregnancy and birth complications, drugs and medications
Both older maternal and paternal age at conception are linked to higher rates of ASD. A meta-analysis found that mothers over 35 had a 1.5 times higher odds of having a child with ASD compared to mothers aged 25-29 . Advancing paternal age over 40 also confers increased risk, possibly due to the accumulation of de novo mutations in sperm .
Exposure to traffic-related air pollution, particularly particulate matter, during pregnancy and early life has been associated with ASD . A study in California found that children living in areas with the highest levels of traffic-related air pollution were 3 times more likely to be diagnosed with ASD .
Maternal influenza infection, prolonged fever, and autoimmune conditions during pregnancy may increase the likelihood of ASD in offspring, potentially by altering foetal brain development . In the CHARGE study, mothers who reported influenza or fever lasting over one week had a 2-fold increased risk of having a child with ASD. Diabetes, hypertension, and obesity during pregnancy have been linked to elevated autism risk. A study found that mothers with gestational diabetes had a 1.4 times higher chance of having a child with ASD, while pre-pregnancy obesity conferred a 1.6 times greater risk . Preterm birth, low birth weight, and neonatal hypoxia have shown associations with ASD [8,9]. In a study of ex-preterm infants, those who screened positive for ASD had higher rates of low birth weight, neonatal seizures, and brain abnormalities on MRI .
The use of valproic acid, an anticonvulsant and mood stabiliser, during pregnancy has been associated with a 3-5 fold increased risk of ASD in offspring . Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has also been suggested to influence ASD risk, although evidence is mixed . It’s important to note that these exposures show an association, not necessarily a causal link, with ASD. Most children exposed to these risk factors do not develop autism, and conversely, many children with ASD have no known environmental exposures. The timing, duration, and intensity of exposures likely interact with genetic predisposition in complex ways .
Rather than acting in isolation, genetic and environmental factors probably combine to influence ASD risk through gene-environment interactions. Certain environmental exposures may have different effects depending on an individual’s genetic background. For example, some studies suggest that prenatal vitamin supplementation or higher folate intake may reduce ASD risk, but this protective effect may depend on the mother’s and child’s genotype related to folate metabolism . Variants in genes involved in detoxification and immune function could also modify the effects of toxicant and infection exposures .
Hellbound and Down 