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!