The DOI matches its Crossref record; 128 of the 132 references it cites were found in a registry or an index.
How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis
Abstract
Recently higher rates of autism diagnosis suggest involvement of environmental factors in causing this developmental disorder, in concert with genetic risk factors. Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase. Methionine synthase activity is required for dopamine-stimulated phospholipid methylation, a unique membrane-delimited signaling process mediated by the D4 dopamine receptor that promotes neuronal synchronization and attention, and synchrony is impaired in autism. Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects. On the basis of these observations, a "redox/methylation hypothesis of autism" is described, in which oxidative stress, initiated by environment factors in genetically vulnerable individuals, leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.
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“Accumulating evidence suggests that a common feature in autism cases may be oxidative stress, the mechanism through which environmental factors exert their deleterious effects, which may be further exacerbated by the interaction of genetically susceptible alleles [96–100].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [97]
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1 retracted
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Modabbernia, A., Velthorst, E., & Reichenberg, A. (2017) · Molecular Autism · doi:10.1186/s13229-017-0121-4 · Cited by 809
Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723
Environmental toxicants and autism spectrum disorders: a systematic review
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Redox dysregulation, neurodevelopment, and schizophrenia
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Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses
Frustaci, A., Neri, M., Cesario, A., Adams, J. B., Domenici, E., Bernardina, B. D., & Bonassi, S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.03.011 · Cited by 383
Metadata
- Authors
- Deth, R., Muratore, C., Benzecry, J., Power-Charnitsky, V.-A., & Waly, M.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Deth, Richard
- Venue
- NeuroToxicology
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 29
- Issue
- 1
- Pages
- 190-201
- ISSN
- 0161-813X (ISSN-L)
- OpenAlex
- W2167943688
- Cited by
- 325
- References
- 132
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 12 · 2021: 16 · 2020: 17 · 2019: 11 · 2018: 17 · 2017: 16 · 2016: 15 · 2015: 28 · 2014: 27 · 2013: 20 · 2012: 34
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroToxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Keywords
- autism spectrum disorder, oxidative stress, DNA methylation, sulfur metabolism, methionine synthase, vitamin B12, folic acid, dopamine signaling, dopamine D4 receptor, phospholipid methylation, neural network synchronization, genetic polymorphism, environmental toxic exposure
- MeSH terms
- Animals, Autistic Disorder, Environment, Humans, Methylation, Models, Biological, Oxidation-Reduction, Sulfur, Oxidative Stress, Receptors, Dopamine D4
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