Post on 08-Nov-2014
description
Irva Hertz-Picciotto
University of California Davis
MIND Institute
Autism and the environment:
Early life causes
Neurobiologic basis:aberrant brain development
• Genes
• Environmental factors
• Public health: ways to intervene
What Causes Autism?
Is the Incidence of Autism
Truly Rising?
autism incidence, by 5 years of age:
rose 7-fold (=600%)
Comparing 1990 births to
2001 births in California
Hertz-Picciotto & Delwiche, Epidemiology 2009
Comparing 1990 births to
2001 births in California
Hertz-Picciotto & Delwiche, Epidemiology 2009
Autism
incid
ence p
er
10,0
00 About 1/3 of this increase
can be explained by changing criteria& better diagnosis
• Environmental chemicals (air pollution, metals) ?
• Household products (pesticides, phthalates) ?
• Vitamins, nutritional deficiencies ?
• Viruses, bacteria?
• Gestational, perinatal conditions (obesity,
diabetes) ?
• Fertility treatments & other medical interventions
?
• Medications ?
• Maternal reproductive characteristics ?
Modifiable Causes of Autism:State of the Science 2013
Genes & Environment
FBE
GH
D
Multifactorial causation
A
C
B
D
Gene 2
Maternal metabolic condition
Pesticide
Gene 1 Gene 2
Metabolic condition
Maternal
NutritionHousehold chemical
Delivery procedure
Air pollution
A
C
B
D
FBE
GH
D
Timing matters!!
A
E
Conception
CB
F
D
G
Birth
H K
Diagnosis
K
H
The CHARGE Study
*CHildhood Autism Risks from
Genetics and the Environment
1. Air Pollution
CHARGE Study Results
1. Air Pollution
Children whose mother lived within
2/10ths of a mile of a freeway had 90%
greater risk for developing autism.
CHARGE Study Results
Volk et al, Environmental Health Perspectives 2011
Volk et al, JAMA Psychiatry 2012
Becerra et al, Environmental Health Persp 2012
1. Air Pollution
2. Maternal Nutrition
CHARGE Study Results
0
10
20
30
40
50
60
70
80
90
100
B3 B2 B1 P1 P2 P3 P4 P5 P6 P7 P8 P9
Autism TD
* * *
*
†
Prenatal Vitamin Supplements
-3 -2 -1 1 2 3 4 5 6 7 8 9
Months Before or During Pregnancy
Schmidt et al, Epidemiology 2011; Amer J Clin Nutrition 2012
OR for autism in child
= 0.6 (95%CI: 0.4 to 0.9)
Per
cent
Rep
ort
ing P
renat
al V
itam
in
Case
mothers
Control mothers
Maternal Nutrition
• Inter-pregnancy interval
• Preconception folic acid reduces
risk for neural tube defects (NTDs)
• 1998: Fortification of cereals & grains with folic acid
• Folic acid/folate is required for basic cell functions:
DNA synthesis, repair and methylation
• Interaction with genes
Schmidt et al, Epidemiology 2011; Amer J Clin Nutrition 2012
Cheslack-Postava Pediatrics 2011
Suren et al JAMA 2013
1. Air Pollution
2. Maternal Nutrition
3. Acute Infection
CHARGE Study Results
3. Infection/Inflammation
Children whose mother had a fever
during pregnancy and did not take
anything for it were at 2 ½ times the risk
for autism
CHARGE Study Results
Zerbo et al, J Autism Dev Disorders 2013
Identify modifiable factors
Goal: to intervene & prevent autism!
Environmental factors in autism
= big return on investment!
Budget
• $4 million annual NIH allocation for
environment, vs. $50-80 million for genes
• $4 million allocation has not been
realized in 2013.
Sequestration
Investigators & Collaborators• UC Davis CCEH
Isaac PessahRobin HansenCheryl WalkerJudy Van de WaterPaul AshwoodRebecca SchmidtDeborah BennettJeffrey GreggPeter Green
• Students/PostdocsMichelle WiestJanie SheltonStephen McKeanOusseny ZerboPaula KrakowiakVirginia ChaidezKristen Lyall
• UC DavisDaniel TancrediFlora TassoneJanine LasalleSally OzonoffKathleen Angkustsiri
• Univ of Stockholm Aake Bergman
• USC (Southern Calif)Pat LevittDan CampbellRob McConnellHeather Volk
• Johns HopkinsLi-Ching LeeRebecca Harrington
• U WashingtonEvan EichlerSanthosh Somaranjan
• UCSFLauren Weiss
• Penn StateScott Selleck
• SynapdxStan Letovsky
• NIOSHErin McCanlies
• Emory UnivPenelope Howards
Special Appreciation to…
thousands of families who
generously give their time to
participate in research
Environmental Research
on Autism
• Modest investment & huge returns
• Public health perspective: prevention
• A gift to children:
a productive life,
engagement in social relationships
independent living
End
Thank you!