Can chemicals
cause autism?
Michael Li
Anne Lor
Richard Li
Brian Tang
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998970920
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998951282
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
Autism Neuropathology
The brains of autistic individuals develop abnormally.
● Overdevelopment of regions of the brain responsible for
social behavior
o Frontal Cortex
o Temporal Cortex
o Amygdala
● Abnormalities in the white matter of an autistic brain
o Increased amounts of short-range connections
 Savants
o Decreased amounts of long-range connections
Causes of Autism
● No concrete evidence linking a chemical agent to
autism.
● Some possible environmental chemical causative
agents include:
o Lead
o Mercury
o Valproic Acid
o Paracetamol
Valproic Acid
● anticonvulsant
● treat seizures,
prevent migraine
headaches, and
the treatment of
epilepsy
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
Rodent Model
● Mice were injected with valproic acid
● In utero exposure of VPA resulted in
physical malformations
○ also showed signs of ASD
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
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(?)
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
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
Summary Slide
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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.
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:
Brain Res., 1408 (2011), pp. 8–16
behavioral
changes
and
liver
parameters
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.