Four things you should know about environmental autism...
Transcript of Four things you should know about environmental autism...
Craig NewschafferDirector, AJ Drexel Autism Institute
Drexel University
Four things you should know about environmental autism risk factors
Outline
What is a “risk factor”
What is “environment”① Environmental risk factors do contribute to causing
autism
② Environmental risk factors are challenging for scientists to discover and confirm
③ The amount of increased risk any one environmental risk factor conveys to the individual is likely quite small
④ However, the overall impact in the population can be quite large
Environmental risk factors with supporting evidence under study now
Time for questions
What is a “risk factor”?
Something that affects the chance of an outcome
chance = probability
…so, there is some math thinking involved.
What does a 30% chance of rain mean?
What is a “the environment”?
Everything that is not heritable…
① Environmental risk factors do contribute to causing autism
① Environmental risk factors do contribute to causing autism
Family studies contrast recurrence of a condition among family members of different known “relatedness” to estimate heritability
Autism twin studies
Heritability estimates from modern twin studiestend to be 50%-60%, with some (higher) exceptions
Other recent family studies generated higher (>80%) heritability estimates
GENES
ENVIRONMENT
Multifactorial causation
Z YS
TU V
X
W
① Environmental risk factors do contribute to causing autism
Single factor causation
G
① Environmental risk factors do contribute to causing autism
Gene-environment interaction
G E
① Environmental risk factors do contribute to causing autism
Gene-environment interaction
G E
Heritability in family studies is over-estimated
① Environmental risk factors do contribute to causing autism
Dev Med Child Neurol, 1994
Stromland et al. Dev Med Child Neurol 1994
Proof of principle exposure example
① Environmental risk factors do contribute to causing autism
② Environmental risk factors are challenging for scientists to discover and confirm
The environment is everything that is not heritable…
② Environmental risk factors are challenging for scientists to discover and confirm
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
3,000 high volumechemicals
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
80,000 new synthesized chemicals
3,000 high volumechemicals
200 detected in blood/urine of all
Americans
8-10 synthesized chemicals proven as developmental
neurotoxicants
Source: Landrigan and Goldman Health Aff 2012
② Environmental risk factors are challenging for scientists to discover and confirm
However<20% detectable chemicals adequately screened for neurodevelopmental effects
Source: Yuen et al. Nat Neurosci 2018
② Environmental risk factors are challenging for scientists to discover and confirm
Interrogation of the whole genome (genomics) is now common
② Environmental risk factors are challenging for scientists to discover and confirm
Interrogation of the whole “exposome” in its earliest days
Rappaport and Smith, Science 2010
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Risk ratio = 1.9
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Risk ratio = 1.9(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Prenatal SSRI absent
1.5%
Risk ratio = 1.9
Prenatal SSRI present
2.7%
(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
Prenatal SSRI absent
1.5%
Risk ratio = 1.9
Prenatal SSRI present
2.7%
1.2% absolute differencein risk
(1.9 = 2.7% / 1.5%)
③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small
④ However, the overall impact in the population can be quite large
④ However, the overall impact in the population can be quite large
Risk ratio = 2.3 for each standard deviation of PM2.5
④ However, the overall impact in the population can be quite large
Risk ratio = 2.3 for each standard deviation of PM2.5
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
One SD belowthe mean
1.5%
Risk ratio = 2.3 for each standard deviation of PM2.5
One SD abovethe mean
3.5%
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
One SD belowthe mean
1.5%
Risk ratio = 2.3 for each standard deviation of PM2.5
One SD abovethe mean
3.5%
2% absolute differencein risk
(2.3 = 3.5% / 1.5%)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
ASDprevalence
8.5%
ASDprevalence
0.1%
Risk ratio = 2.3 for each standard deviation of PM2.5
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
Population ASD prevalence down from 1.5% to 1.4% (3% reduction in ASD cases in the population overall)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
④ However, the overall impact in the population can be quite large
Births categorized by amount of prenatal exposure to air pollution (PM2.5)
Population ASD prevalence down from 1.5% to 0.8% (47% reduction in ASD cases in the population)
④ However, the overall impact in the population can be quite large
Specific environmental risk factors with supporting evidence under study now
• Parental age• Pre-, peri-, and neonatal
complications– Low birth weight / SGA– Infection
• Prenatal medication use• Short interpregnancy interval• Prenatal (preconception) nutrition
– Folate • Prenatal (preconception) air
pollution• Endocrine disrupting chemicals
www.prhe.ucsf.edu/info
www.drexel.edu/[email protected]
QUESTIONS?