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Can chemicals cause autism?

Can chemicals cause autism?. Michael Li 1001201772 Anne Lor 998970920 Richard Li 1001980421 Brian Tang 998951282. What is Autism. Autism is a neurodevelopmental disorder that results in: Deficit in social skills from infancy lack of communicative ability Repetitive interests

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Can chemicals cause autism?

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  1. Can chemicals cause autism? Michael Li 1001201772 Anne Lor 998970920 Richard Li 1001980421 Brian Tang 998951282

  2. What is Autism Autism is a neurodevelopmental disorder that results in: • Deficit in social skills from infancy • lack of communicative ability • Repetitive interests Autism is a biological genetic disorder: • Monozygotic twins share 90% concordance • Dizygotic twins share 10% concordance

  3. Autism Neuropathology The brains of autistic individuals develop abnormally. • Overdevelopment of regions of the brain responsible for social behavior • Frontal Cortex • Temporal Cortex • Amygdala • Abnormalities in the white matter of an autistic brain • Increased amounts of short-range connections • Savants • Decreased amounts of long-range connections

  4. Causes of Autism • No concrete evidence linking a chemical agent to autism. • Some possible environmental chemical causative agents include: • Lead • Mercury • Valproic Acid • Paracetamol

  5. Valproic Acid • anticonvulsant • treat seizures, prevent migraine headaches, and the treatment of epilepsy

  6. Studies of Valproic Acid and ASD • Fetal Valproate Syndrome • Linked to increased risk of ASD • 11 year study on cognitive development of children born to mothers with epilepsy

  7. Rodent Model • Mice were injected with valproic acid • In utero exposure of VPA resulted in physical malformations • also showed signs of ASD

  8. Epigenetics in ASD? • VPA can inhibit histone deacetylases • genetic material: • negatively-charged DNA • positively-charged histones • access to genes decreases with increasing strength of DNA/histone interactions • acetylation removes positive charge from histones • DNA/histone interactions broken, leading to increased gene expression • deacetylation reintroduces positive charge • DNA/histone interactions restored, leading to decreased gene expression

  9. A Possible Mechanism • VPA prevents deacetylation → increased gene expression • ASD caused by brain tissue overgrowth in areas controlling social/emotional functioning(?) • increased gene expression leads to increased growth of neural tissue(?)

  10. Other Possible Chemical Agents Paracetamol (acetaminophen) • Study found that children who had pre-natal exposure to paracetamol for more than 28 days had neurodevelopmental outcomes • Suggested correlation between prenatal paracetamol use and autism prevalence • However, no definitive evidence to suggest correlation = causation

  11. Other Possible Chemical Agents Lead • Autistic children tend to have significantly higher lead blood levels in comparison to children who do not have autism • Suggests that lead is a possible causative agent for autism, but no definitive evidence yet • Again, no evidence to suggest correlation = causation

  12. Summary Slide • ASD is a neurodevelopmental disorder that impairs communicative ability • Individuals with autism show abnormal brain development characterized by the overdevelopment of the frontal cortex, temporal cortex and amygdala. • Studies conducted of children exposed to valproic acid prenatally showed a higher risk of neurodevelopmental disorders • Rodent model is used to further investigate the link between prenatal valproic acid exposure and ASD • Valproic acid inhibits histone deacetylation, thus leading to increased gene expression and tissue overgrowth in areas of the brain involved in emotional and social functioning • Correlation between pre-natal paracetamol use and prevalence of autism exists. However, there is a lack of evidence to suggest that paracetamol causes autism. • Autistic children tend to have higher lead blood levels than healthy children. Although a correlation exists, no mechanism is established on how lead may cause autism.

  13. References American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: 4th ed. Washington, DC: American Psychiatric Association V. Bambini-Junior, L. Rodrigues, G.A. Behr, J.C. Moreira, R. Riesgo, C. Gottfried Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parametersBrain Res., 1408 (2011), pp. 8–16 • Takuma, K., Ago, Y., Matsuda, T., Hashimoto, H., Hayata-Takano, A., Takano, E., et al. (2014). Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism. Pharmacology Biochemistry and Behavior, 126C, 1-43. Chomiak T, Turner N, Hu B. 2013. What we have learned about autism spectrum disorder from valproic acid. Pathology Research International, 2013: 712758. Brandlistuen, RE., Ystrom, E., Nulman, I., Koren, G., and Nordeng, H. 2013. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol. 42(6):1702. El-Ansary AK., Bacha, AB., and Ayahdi, LY. 2011. Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia. Clin Biochem. 44(13): 1116-1120.

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