Etiology of Autism - PowerPoint PPT Presentation

1 / 24
About This Presentation
Title:

Etiology of Autism

Description:

Replicate studies of persistent measles infection in autism cases vs healthy controls ... re abnormal measles antibody titers and persistent measles infection ... – PowerPoint PPT presentation

Number of Views:40
Avg rating:3.0/5.0
Slides: 25
Provided by: mariembris
Category:

less

Transcript and Presenter's Notes

Title: Etiology of Autism


1
Etiology of Autism
  • Institute of Medicine
  • Immunization Safety Review Committee
  • National Academy of Sciences
  • Washington, D.C.
  • March 8, 2001

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
2
Marie Bristol-Power, Ph.D.
  • Special Assistant for Autism
  • Office of the Director
  • National Institute for Child Health Human
    Development (NICHD)
  • The National Institutes of Health (NIH)

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
3
No Single Cause No Single Cure
  • Genetic
  • Infectious
  • Neurologic
  • Metabolic
  • Immunologic
  • Environmental

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
4
Etiological Hypotheses
  • No single cause no single cure
  • Early onset autism vs regressive autism
  • Regression in other disorders
  • Retts syndrome
  • Glutaric Aciduria

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
5
Some Possible Mechanisms for Immune Developmental
Disorders
  • Inadequate protection against viral or other
    pathogens results in fetal/child infection
  • Maternal immune defect results in inadequate
    protection or autoimmune attack of developing
    fetal brain
  • Pre or postnatal genetic immune defect in child
    plus antigenic trigger result in autoimmune
    attack of brain

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
6
Immune findings in autismWarren et al.
  • C4B null allele
  • 25/50 subjects vs. 17/85 controls
  • Extended HLA haplotype B44-S30-DR4
  • 14/50 subjects vs. 2/85 controls
  • HVR-3 sequence 1
  • 17/50 subjects vs. 2/85 controls

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
7
Limitations in Immune Hypotheses of Autism
  • No autopsy studies of brains from individuals
    with autism have demonstrated immune pathology
  • Comparison across studies difficult autism
    assessment, control groups, and immune measures
    vary across studies

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
8
Limitations in Immune Hypotheses of Autism
  • No immune mechanism has been elaborated to
    explain how immune defects alter brain anatomy or
    physiology in a specific pathway that results in
    autism
  • There is no immune animal model for autism
  • Treatment studies do not support clinical use of
    IVIG

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
9
NICHD/NIDCD
  • Network on the Neurobiology and Genetics of
    Autism
  • Collaborative Programs of Excellence in Autism
    (CPEAs)

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
10
CPEA Network
  • 10 multidisciplinary programs
  • Each a unique research program
  • All study etiology, brain structure /or
    function, developmental course of autism
  • Collaborate on studies that no single project can
    carry out alone
  • Common diagnostic core measures

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
11
U. of Chicago Volkmar/Lord/Smalley
U. of Washington CPEA Dawson
U. of Rochester CPEA Rodier
Albert Einstein College of Medicine
CPEA Dunn/Rapin
E. Kennedy Shriver Ctr. NIDCD/CPEA Tager-Flusberg/
Folstein
Utah State McMahon
MGH/Harvard Tager-Flusberg/Folstein
U. of Utah CPEA McMahon
Brigham Young U. McMahon
Yale Child Study Ctr. CPEA Vokmar/Lord/Smalley
Johns Hopkins Rogers/Pennington
UCLA CPEA Sigman
U. of Pittsburgh/Carnegie Mellon
CPEA Minshew/Carpenter
UCLA Volkmar/Lord/Smalley
Case-Western Reserve U. Minshew/Carpenter
U.C. Irvine CPEA Spence/Filipek
U. of Colorado Health Sciences Ctr. U. of
Denver Rogers/Pennington
CPEA Main Site - Principal Investigator
CPEA Subcontract Site
Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
12
Some CPEA Research Findings
  • Genetic hotspots in autism (with international
    consortium), esp. Ch.7
  • Hox A1 gene
  • Chromosome 15

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
13
Some CPEA findings
  • Evidence of autism behaviors by 8 - 12
    mos
  • Also evidence of subgroup with later regression
    after normal development
  • Functional brain differences in processing social
    and auditory info
  • Immune indicators, possible immune assay found in
    autism
  • Differences in head circumference, children and
    adults

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
14
CPEA Autism Regression/ Vaccination Study
  • Co-funded by Centers for Disease Control in
    Atlanta, National Immunization Program
  • Assess temporal association between MMR
    vaccination and onset of autism (early onset vs
    regressive)
  • Replicate studies of persistent measles infection
    in autism cases vs healthy controls

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
15
CPEA Autism Regression/ Vaccination Study - Stage1
  • 1600 well-diagnosed cases of autism
  • 1250 healthy controls
  • individual vaccination records
  • records of onset of autism - ADI-R
  • age of onset
  • age of recognition
  • age of diagnosis

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
16
CPEA Autism Regression/ Vaccination Study - Stage2
  • Replicate findings re abnormal measles antibody
    titers and persistent measles infection

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
17
  • 250 early onset autism cases
  • 250 regressive autism cases
  • 250 healthy controls matched to early onset
  • 250 healthy controls matched to regressive cases

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
18
CPEA Autism Regression/ Vaccination Study
  • http//www.nichd.nih.gov/autism/

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
19
The Longitudinal Cohort Study of Environmental
Effects on Child Health and Development
  • NICHD/NIH
  • CDC
  • EPA
  • Other agencies

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
20
Children -- Increased Vulnerability to
Environmental Exposures
  • Critical windows of vulnerability during
    development
  • Children have immature mechanisms for
    detoxification
  • Differences in metabolism and behavior may yield
    higher exposure in the same environment

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
21
Children -- Increased Vulnerability to
Environmental Exposures
  • Critical windows of vulnerability during
    development
  • Children have immature mechanisms for
    detoxification
  • Differences in metabolism and behavior may yield
    higher exposure in the same environment

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
22
Why a longitudinal study?
  • Links between many exposures and childrens
    health not adequately investigated (especially
    mixtures)
  • Infers causality
  • Life-stage effort
  • Timing of exposures
  • Timing of outcome
  • Typical studies limited in size scope
  • National resource for other studies

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
23
Aims
  • Do environmental agents affect the health and
    development of children?
  • How do environmental agents (timing, mixtures,
    interactions) affect childrens health and
    development?
  • Are certain conditions exacerbated by
    environmental exposures?

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
24
Longitudinal Cohort Study
  • http//www.nichd.nih.gov/despr/cohort/

Marie Bristol-Power, Ph.D., NICHD/NIH
NAS/IOM March 8, 2001
Write a Comment
User Comments (0)
About PowerShow.com