Autism Physiology

A Different Perspective

Eugene S. Justus, D.O.Speedway Family Physician1011 Main Street, Suite 110

Speedway, IN 46224

Indiana Osteopathic Association Convention, May 3, 2013

2

• 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.

Objectives

3

• 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

Conflict of Interest

4

• Any discussion of the treatment for Autism is “off- label” except for the use of Risperidone and Aripiprazole for the treatment of irritability.

• Irritability is not a core defect of Autism Spectrum Disorders (ASD).

Disclaimer

5

6

7

• Impaired Communication Skills

• Impaired Social Interactions

• Repetitive, Compulsive, and/or Stereotyped Behavior

What is Autism Spectrum Disorder

8

1 in 150 children in 2008

1 in 101 children in 2010

1 in 83 Hoosier school children in 2011

The Numbers

9

1 in 50Children!

National Health Statistic Report, Number 65, March 20, 2013

National Survey of Children's Health 2011-2012

10

Hoosier Children

11

• Over 100 genetic abnormalities associated with ASD

• 18 of 23 Chromosomes associated with ASD

Genetics

12

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 AutismArch Gen Psychiatry. 2011;68(11):1095-1102. doi:10.1001/archgenpsychiatry.2011.76.

13

• 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

• The Rise in Autism and the Role of Age at Diagnosis, Irva Hertz-Picciottoa,b and Lora Delwichea, Epidemiology 2009;20: 84–90

Better Counting?

14

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 born 1987, 1990,

1994, and 1997. 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 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"

15

The Spectrum

ADD/ADHD

Sensory ProcessingDisorder

AspergerSyndrome

PDD-NOS

Autism Disintegrative Disorder

RhettsSyndrome

16

Chronic Active Pathophysiology

Abnormal Brain Cell

Physiology

17

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

Toxic Injury

18

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 lipoproteinsChambers jJE. Proc Nat Acad. Sci. Sept 2nd 2008 105 (35) 12639-12640

Toxic Injury and Genetic Predisposition

19

Paraoxonase gene variants are associated with autism in North America, but not Italy: possible regional specificity in gene-environment interactins

• Persico AM et al• Molecular Psychiatry (2005) 1-11

Toxic Injury and Genetic Predisposition

20

• 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.

• Ashwood et al, Autism , Oxidative Stress, Inflammation, and Immune Abnormalities. Ed by Chauhan, Chauhan, Brown.

Immune Abnormalities

21

Immune Abnormalities

22

Identification of Unique Gene Expression Profile inChildren 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

Immune Abnormalities

23

Oxidative Stress

24

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

Oxidative Stress

25

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

• DA Rosingnol and RE Frye, Molecular Psychiatry (2012) 290-314

Oxidative Stress

26

• 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.

A Chronic Dynamic Encephalopathy

27

• 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.

A Chronic Dynamic Encephalopathy

28

• 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

Summary

29

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.

So What???

30

• 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

Some treatment guides

31

Questions?

And Thank You!