Autism and the environment: Early life causes

Irva Hertz-Picciotto University of California Davis MIND Institute

Neurobiologic basis: aberrant brain development

What Causes Autism?

Genes Environmental factors

Public health: ways to intervene

Is the Incidence of Autism Truly Rising?

Comparing 1990 births to 2001 births in California

autism incidence, by 5 years of age:

rose 7-fold (=600%)

Hertz-Picciotto & Delwiche, Epidemiology 2009

Autism incidence per 10,000

About 1/3 of this increase Comparing 1990 births to can be explained by 2001 births in California changing criteria
& better diagnosis

Hertz-Picciotto & Delwiche, Epidemiology 2009

Modifiable Causes of Autism: State of the Science 2013

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 ?

Genes & Environment

Multifactorial causation
Gene 2

Gene 1

A
C

B D

Pesticide

Metabolic condition

Maternal Nutrition Gene 2 Household E B chemical F D Maternal Delivery G metabolic H procedure condition Air pollution

Timing matters!!

A C

B D

F G

E B

D
H K
Diagnosis

Conception

Birth

H G

*CHildhood Autism Risks from Genetics and the Environment

The CHARGE Study

CHARGE Study
Results

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.
Volk et al, Environmental Health Perspectives 2011 Volk et al, JAMA Psychiatry 2012 Becerra et al, Environmental Health Persp 2012

CHARGE Study
Results

1. Air Pollution 2. Maternal Nutrition

Prenatal Vitamin Supplements TD Autism

100

Percent Reporting Prenatal Vitamin

90 80 70 60 50 40

Control mothers

Case mothers

* *

30
20 10 0

OR for autism in child = 0.6 (95%CI: 0.4 to 0.9)

B3 B2 B1 P1

-3 -2 -1 1 2 3 4 5 6 7 8 9 P2 P3 P4 P5 P6 P7 P8 P9 Months Before or During Pregnancy

Schmidt et al, Epidemiology 2011; Amer J Clin Nutrition 2012

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

CHARGE Study
Results

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 times the risk for autism
Zerbo et al, J Autism Dev Disorders 2013

big return on investment!

Identify modifiable factors Goal: to intervene & prevent autism!

Environmental factors in autism =

Budget
$4 million annual NIH allocation for environment, vs. $50-80 million for genes

Sequestration
$4 million allocation has not been realized in 2013.

Investigators & Collaborators

UC Davis CCEH UC Davis Isaac Pessah Daniel Tancredi Robin Hansen Flora Tassone Cheryl Walker Janine Lasalle Judy Van de Water Sally Ozonoff Paul Ashwood Kathleen Angkustsiri Rebecca Schmidt Deborah Bennett Univ of Stockholm Jeffrey Gregg Aake Bergman Peter Green USC (Southern Calif) Students/Postdocs Pat Levitt Michelle Wiest Dan Campbell Janie Shelton Rob McConnell Stephen McKean Heather Volk Ousseny Zerbo Paula Krakowiak Johns Hopkins Li-Ching Lee Virginia Chaidez Rebecca Harrington Kristen Lyall U Washington Evan Eichler Santhosh Somaranjan UCSF Lauren Weiss Penn State Scott Selleck Synapdx Stan Letovsky NIOSH Erin McCanlies Emory Univ Penelope 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!