Autism Physiology
A Different Perspective
Eugene S. Justus, D.O.
Speedway Family Physician
1011 Main Street, Suite 110
Speedway, IN 46224
Indiana Osteopathic Association Convention, May 3, 2013
Objectives
• Understand that Autism is epidemic
• Support the perspective that Autism is a whole body
disease.
• Introduce the role of toxic injury, oxidative stress,
and immune abnormalities in Autism Spectrum
Disorders (ASD).
• Support the concept that Autism is a dynamic
encephalopathy as opposed to a fixed
encephalopathy.
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Conflict of Interest
• Dr. Justus provides consultative services for children
and families affected by Autism Spectrum Disorders
at Speedway Family Physicians, Community
Westview Physicians
• Dr. Justus has a son with the diagnosis of Autism
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Disclaimer
• Any discussion of the treatment for Autism is “offlabel” except for the use of Risperidone and
Aripiprazole for the treatment of irritability.
• Irritability is not a core defect of Autism Spectrum
Disorders (ASD).
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What is Autism Spectrum Disorder
• Impaired Communication Skills
• Impaired Social Interactions
• Repetitive, Compulsive, and/or
Stereotyped Behavior
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The Numbers
1 in 150 children in 2008
1 in 101 children in 2010
1 in 83 Hoosier school children in 2011
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National Survey of Children's Health 2011-2012
1 in 50
Children!
National Health Statistic Report, Number 65, March 20, 2013
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Hoosier Children
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Genetics
• Over 100 genetic abnormalities
associated with ASD
• 18 of 23 Chromosomes associated with
ASD
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California Autism Twin Study
Conclusion Susceptibility to ASD has
moderate genetic heritability and a
substantial shared twin environmental
component.
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Arch Gen Psychiatry. 2011;68(11):1095-1102. doi:10.1001/archgenpsychiatry.2011.76.
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Better Counting?
• UC Davis M.I.N.D. Institute study shows California's
autism increase not due to better counting,
diagnosis (2009)
• “Autism incidence in California shows no sign yet of
plateauing,” Hertz-Picciotto and Delwiche said in
their study
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The Rise in Autism and the Role of Age at Diagnosis, Irva Hertz-Picciottoa,b and Lora
Delwichea, Epidemiology 2009;20: 84–90
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Better Counting?
We investigated if shifts in the coding of qualifying conditions in the
California Department of Developmental Services (DDS) have contributed to
the increase in California children with autism observed in recent years.
Qualifying condition codes for mental retardation (MR) and autism in DDS
electronic files were compared to hard-copy records for samples of children
Contrary to
expectations, we did not find evidence of a
coding shift from "MR only" to "both MR
and autism" or an increase in the proportion of children with
born 1987, 1990, 1994, and 1997.
coded autism who lacked supportive diagnostic documentation in records
(possible "misclassifications "). These results indicate that changes in DDS
coding practices are unlikely to explain the increase in DDS clients with
autism.
Journal of Autism and Developmental Disordorders May 29, 2009
"Investigation of Shifts in Autism Reporting in the California Department of
Developmental Services"
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The Spectrum
ADD/
ADHD
Sensory
Processing
Disorder
Asperger
Syndrome
PDDNOS
Autism
Disintegrative
Disorder
Rhetts
Syndrome
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Chronic Active Pathophysiology
Genetic
Predisposition
Immune
Deregulation
Abnormal
Brain Cell
Physiology
Toxic Injury
Oxidative
Stress
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Toxic Injury
A study by researchers at The University of Texas Health Science Center at San Antonio reveals
a multiple-digits increase in the rate of autism for every 1,000 pounds of mercury released
environmentally in Texas counties.
The study does not prove causation of autism by mercury, researchers are quick to point out.
The study compared mercury totals reported for 2001 in the 254 Texas counties to the rate of
autism and special education services in nearly 1,200 Texas school districts. The districts, which
range from urban to small metro to rural, enroll 4 million Texas children.
“The main finding is that for every 1,000 pounds of
environmentally released mercury, we saw a 17 percent
increase in autism rates,” said lead author Raymond F.
Palmer, Ph.D., associate professor in the Health Science
Center’s department of family and community medicine.
Health & Place 12 (2006) 203–209
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Toxic Injury and Genetic Predisposition
Paraoxonase protects against organophosphates
There is a gene PON 1 that codes for paroxonase.
Certain single nucleotide polymorphisms (SNP’s) can
account for a 40 fold variability in activity
PON1 purpose in Redox regulation and preventing
oxidation of lipoproteins
Chambers jJE. Proc Nat Acad. Sci. Sept 2nd 2008 105 (35) 12639-12640
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Toxic Injury and Genetic Predisposition
Paraoxonase gene variants are associated with autism
in North America, but not Italy: possible regional
specificity in gene-environment interactins
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Persico AM et al
Molecular Psychiatry (2005) 1-11
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Immune Abnormalities
• There is extensive cross talk between the immune
system and then nervous system.
• Neurotransmitters can modulate the immune
responses.
• The immune system can directly alter neurologic
pathways which can affect mood and behaviors
• Altered immune function has been associated with
ASD for nearly 40 years.
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Ashwood et al, Autism , Oxidative Stress, Inflammation, and Immune Abnormalities. Ed by
Chauhan, Chauhan, Brown.
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Immune Abnormalities
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Immune Abnormalities
Identification of Unique Gene Expression Profile in
Children with Regressive Autism Spectrum Disorder
(ASD) and Ileocolitis
Authors demonstrated a profile for ASD that was
different from Crohns Disease and Ulcerative Colitis,
but with some overlap with both.
Krigsman et al, PLOS ONE www.plosone.org 1 March 2013 | Volume 8 | Issue 3 e58058
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Oxidative Stress
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Oxidative Stress
An Open Label Trial of Methylcobalamin and Folinic Acid in
Autistic children
• Supplementation of methylcobalamin (Me-B12) and
folinic acid for 3 months
• Improved glutathione and precursors
• Improved Vineland Behavioral Adaptive Behavioral
Scales
Jill James, PhD. Journal of Clinical Nutrition
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Oxidative Stress
Mitochondrial dysfunction in austism spectrum
disorders: a systematic review and meta-analysis
• Findings suggest children with ASD have a variety of
mitochondrial dysfunctions (MD)
• The prevalence of developmental regression, seizures, motor
delay were higher with ASD/MD vs the general ASD
population
• The over all evidence supports MD is associated with ASD
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DA Rosingnol and RE Frye, Molecular Psychiatry (2012) 290-314
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A Chronic Dynamic Encephalopathy
• Case #1 in the 1943 Kanner paper.
• Diagnosed with J.R.A. and treated with gold
• Experienced remission of arthritis and autism
symptoms
• Earned a BS degree and lives independentaly.
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A Chronic Dynamic Encephalopathy
• The DSM IV criteria does preclude improvement
• Transient improvement with fever and antibiotics
• Researchers have produced outcome studies and
the notion of recovery
• Reversal of abnormal behavior have been
demonstrated in animal models
•
Herbert, Autism , Oxidative Stress, Inflammation, and Immune Abnormalities. Ed by
Chauhan, Chauhan, Brown.
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Summary
• Autism is epidemic
• Autism is the result of the interaction of genetic
predisposition, toxic injury, immune abnormalities
and oxidative stress
• Autism is not a static, but dynamic encephalopathy
subject whole body pathophysiology
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So What???
You will see more and more of these individuals in
your practices, even if you don’t do pediatrics.
You can have a positive impact on their quality of life
treating them osteopathicly . That is think about
there underlying pathophysiology and address it.
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Some treatment guides
• The Autism Revolution. Whole-body strategies for making life all it can
be, Martha Herbert, MD. PhD. with Karen Weintraub, Ballantine Books
• The Autism Book, What every Parent Needs to Know About Early
Detection, Treatment , Recover, and Prevention, Robert W. Sears, MD.
FAAP. LB Little Brown
• Changing the Course of Autism, A Scientific Approach for Parents and
Physicians, Bryan Jepson, MD. with Jane Johnson, Sentient
• Biomedical Treatments for Autism and PDD, 3rd Edition, William Shaw
PhD
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Questions?
And
Thank You!
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