Autism spectrum disorder: etiology and research tools

​​Explore the genetic complexity of autism spectrum disorder (ASD) and access the tools to further your scientific research in this area.

Download our interactive poster on key cellular pathways in ASD here.

Overview

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• What is autism spectrum disorder?
• Etiology of autism spectrum disorder
• Key cellular pathways in ASD – interactive poster
• Role of biomarkers in ASD
• References

What is autism spectrum disorder?

ASD is a heritable, heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication skills as well as repetitive behavior presenting in early childhood¹. Children with ASD manifest such distinctive behaviors as reduced eye contact, problems with controlling or understanding emotions, and a restricted range of activities and interests.

Etiology of autism spectrum disorder

ASD is a multi-factorial disorder, which may result from genetic and environmental factors. Genetic causes, including gene defects and chromosomal anomalies, have been found in 10%–20% of individuals with ASD². The etiology of ASD is confirmed to be multigenic and highly heterogeneous, with very few of the same genetic variants present in a significant percentage of individuals with ASD³.

Large-scale genetic studies have revealed hundreds of risk genes linked to ASD. ASD-associated genes have been shown to contribute to brain development, neuronal activity, signaling, transcription regulation, and synaptic function⁴. Synapse-related risk genes in ASD encode proteins involved in the formation, stabilization, and maintenance of functional synapses, including cell-adhesion proteins (neuroligins, neurexins, and cadherins), synaptic vesicle cycling proteins SYN1 and SYN2, ion transport proteins such as SCN2A, postsynaptic density proteins SHANK3 and SYNGAP1, and many others³.

Multiple studies have revealed an increased number of de novo mutations in regulatory elements of ASD risk genes in patients ^5–7. Susceptibility genes impacting transcription and chromatin-remodeling pathways include MeCP2, UBE3A, chromodomain helicase DNA binding protein 8 (CHD8), activity-dependent neuroprotector homeobox (ADNP), pogo transposable element derived with ZNF domain (POGZ), fragile X mental retardation protein (FMRP), and RNA binding forkhead box (RBFOX) genes³.

Key cellular pathways in ASD – interactive poster

Mutations in ASD-related genes have been shown to affect three key cellular pathways: synaptic function, translation, and WNT signaling. These pathways are interconnected through neuronal activity. Wnt signaling regulates key transcriptional programs that affect neuronal maturation and neural circuit formation, which are also dependent on synaptic activity during development. Localized translation at the synapse underlies synaptic plasticity and cognition, whereas synaptic translation is stimulated by synaptic activity⁴.

Explore major pathways implemented in ASD with our interactive pathway and find the best tools to advance your research in ASD by reading the popups and product tables that include Abcam's full product offering.

Click on the preview image below to download our interactive poster.

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​Role of biomarkers in ASD 

Early identification and treatment of individuals with ASD can improve their outcomes, but there is a lack of specific tools needed to individualize treatment. Routine use of biomarkers could potentially transform clinical care for patients with ASD by identifying clinically meaningful subgroups within highly heterogeneous populations to allow for more precise, individualized medical care⁸.

Emerging research on potential biomarkers in ASD encompasses genetic, biochemical, metabolomic, immune, and oxidative stress markers as well as neuroimaging, electrophysiologic, physical, and behavioral characteristics.

Biochemical markers include neurotransmitters, hormones, and markers of immune function and inflammation. For example, studies have reported elevated whole-blood serotonin and decreased plasma melatonin levels in individuals with ASD compared to controls^9–11. Furthermore, one study revealed that combined analysis of serotonin, N-acetylserotonin, and melatonin levels could differentiate individuals with autism from controls with 80% sensitivity and 85% specificity¹¹.

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References 

1. American Psychiatric Association, and DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Washington, DC: American Psychiatric Association (2013).
2. Park, H.R., Lee, J.M., Moon, H.E., et al. A short review on the current understanding of autism spectrum disorders. Exp Neurobiol. 25, 1–13 (2016).
3. Rylaarsdam, L., Guemez-Gamboa, A. Genetic Causes and Modifiers of Autism Spectrum Disorder. Front Cell Neurosci. 13, 385 (2019).
4. Quesnel-Vallières, M., Weatheritt, R.J., Cordes, S.P., Blencowe, B.J. Autism spectrum disorder: insights into convergent mechanisms from transcriptomics. Nat Rev Genet. 20, 51–63 (2019).
5. Turner, T.N., Hormozdiari, F., Duyzend, M.H., et al. Genome sequencing of autism-affected families reveals disruption of putative noncoding regulatory DNA. Am J Hum Genet. 98, 58–74 (2016).
6. Turner, T.N., Coe, B.P., Dickel, D.E., et al. Genomic patterns of de novo mutation in simplex autism. Cell. 171, 710–722 (2017).
7. Short, P.J., McRae, J.F., Gallone, G., et al. De novo mutations in regulatory elements in neurodevelopmental disorders. Nature. 555, 611–616.  (2018).
8. Bridgemohan, C., Cochran, D.M., Howe, Y.J., et al. Investigating potential biomarkers in autism spectrum disorder. Front Integr Neurosci. 13: 31 (2019).
9. Hammock E., Veenstra-VanderWeele J., Yan Z., et al. Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems. J. Am. Acad. Child Adolesc. Psychiatry. 51, 712–721.e1 (2012).
10. Gabriele, S., Sacco, R., Persico, A.M. Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis. Eur Neuropsychopharmacol. 24, 919–929 (2014).
11. Pagan, C., Delorme, R., Callebert, J., et al. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders. Transl Psychiatry. 4, e479 (2014).