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Understanding Autism Spectrum Disorder: Potential Causes and Risk Factors

Autism Spectrum Disorder (ASD) is a neurobiological disorder that affects the developing brain and is influenced by both genetic and environmental factors. In this article, we will explore the potential causes and risk factors associated with ASD.

Neuropathologic Studies

Neuropathologic studies have revealed differences in cerebellar architecture and connectivity, limbic system abnormalities, and frontal and temporal lobe cortical alterations, along with other subtle malformations. Brain overgrowth both in terms of cortical size and additionally in terms of increased extra-axial fluid have been described in children with ASD and are areas of ongoing study both in terms of furthering our understanding of its etiology, but also as a potential biomarker.


Genetic Factors

Genetic factors play a role in ASD susceptibility, with siblings of patients with ASD carrying an increased risk of diagnosis when compared to population norms, and a much higher, although not absolute, concordance of autism diagnosis in monozygotic twins. Genome-wide association studies and whole exome sequencing methods have broadened our understanding of ASD susceptibility genes, and learning more regarding the function of these genes can shed light on potential biologic mechanisms.


Environmental Factors

While genetics clearly play a role in ASD’s etiology, phenotypic expression of genetic susceptibility remains extremely variable within ASD. Genetic risk may be modulated by prenatal, perinatal, and postnatal environmental factors in some patients. Prenatal exposure to thalidomide and valproic acid have been reported to increase risk, while studies suggest that prenatal supplements of folic acid in patients exposed to antiepileptic drugs may reduce risk. Advanced maternal and paternal age have both been shown to have an increased risk of having a child with ASD. Maternal infection or immune activation during pregnancy is another area of interest and may be a potential risk factor according to recent investigations. Infants born prematurely have been demonstrated to carry a higher risk for ASD in addition to other neurodevelopmental disorders.


Vaccines and ASD

Despite the hysteria surrounding the now retracted Lancet article first published in 1998, there is no evidence that vaccines, thimerosal, or mercury is associated with ASD. In the largest single study to date, there was not an increased risk after measles/mumps/rubella (MMR) vaccination in a nationwide cohort study of Danish children.



While research continues to reveal factors that correlate with ASD risk, no causal determinations have been made. This leaves much room for discovery with investigators continuing to elucidate new variants conveying genetic risk, or new environmental correlates that require further study. To learn more about ASD and the latest research, visit our website and join the conversation on social media.


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