Transcript Neurodevelopmental Disorders Following Childhood Vaccinations

The Biology of Autism: An
introduction
Associate Professor David W Austin, PhD
Director: Swinburne Autism Bio-Research Initiative (SABRI)
Faculty of Life and Social Sciences
Swinburne University of Technology
Australia
[email protected]
1 out of 6 children are diagnosed with a
developmental disorder and/or behavioural disorder
1 in 166 children are diagnosed with an autism
spectrum disorder
The emergence of a ‘new’ disorder
• Children with a cluster of symptoms that was to
become known as ‘Autism’ were first noticed almost
simultaneously on 2 continents (US and Europe)
around 1940.
• Although initially rare (only 11 cases reported to 1940),
prevalence exponentially increased over the ensuing
decades, reaching a peak of 1 in every 120 children
today.
The genesis of the autism epidemic




Autism was first described in 1943 (Kanner), among
children born in the early 1930s.
By the mid 1980s, 1 in 2,500 was diagnosed with
autism.
By the mid 1990s, 1 in 250 children was diagnosed
with autism
The most recent studies in Australia, the US and UK
show the prevalence of autism to be 1 in 120 children
Autism Prevalence, 1993 - 2003
But aren’t we just getting better at
diagnosing it?
No. The argument that the rise in autism rates are attributable to
improved identification have been dismissed (Blaxhill et al.,
2003; Croen & Graether, 2003)
But isn’t autism genetic?
“There is an autism epidemic. Epidemics
happen because of environmental triggers.”
~Martha Herbert, MD, PhD
Pediatric Neurologist,
Harvard Medical School
So how is the medical system
helping these children?
Australian doctors are authorised to prescribe
over 6,900 different medications. How many
are approved and indicated for use in autism?
None
World Health Organisation:
Management of Mental Disorders
•
•
2 volumes, 632 pages covering management of all DSM-IV listed
disorders.
Typical subheadings include; Description, Diagnosis,
Epidemiology, Course, Prognosis, Management/Treatment.
Example
1. Schizophrenia: All subheadings, 39 pages
2. PDD (incl autism): no subheadings, 1/3 page (p. 475)
“These conditions are difficult to treat and require ongoing
intensive work to achieve even modest gains.”
So how do we
get from this…
To this…
Choices in the face of debate and
uncertainty
•
•
Include plausible and informed hypotheses centrally in
the research agenda
Look not only for environmental cause but also for the
full range of mechanisms and consequences for the
child.
Daring to change
•
Knowing the biological irregularities common to
autism and having plausible causal hypotheses
guides research options.
•
Instead of existing “no treatment” models of
care, we open up a world of opportunity for
research and treatment to improve the autistic
child’s condition and prognosis.
So what are the biological markers
of autism?










Inflam. Bowel Disease
Opioids
Persistent Measles
Reflux Esophagitis
Gastritis
Intestinal permeability
Food Allergies
Heavy Metal Burden
Brain Autoimmunity
GI Dysbiosis











Seizures/Sensory Issues
Perfusion Defects
Purine Disorders
Elevated Ammonia
Sulfation Defect
Serotonin Defect
Dopamine Defect
Omega 3 deficit
Nutritional Deficits
Melatonin Deficit
Thrombophilia
The brains of children with autism are experiencing
severe oxidative stress and inflammation
“decreased glutathione levels and increased oxidative
stress may play a role in the pathology”
~ Kern & Jones (2006). Journal of
Toxicology and Environmental Health.
Prevalence of Autism per 100,000
Children
Higher levels of environmental mercury are
associated with higher rates of autism
“The association between
environmentally released
mercury and special
education rates were fully
mediated by increased
autism rates.”
250
200
R2 = 0.97
~ Palmer et al (2006).
Health & Place.
150
100
50
0
100
150
200
250
Mercury Dose per Child (m icrogram s)
300
Mercury levels in children with autism are
higher than in neurotypical (normal) children
“a significant relation does exist between the
blood levels of mercury and diagnosis of an
autism spectrum disorder.”
~ DeSoto & Hitlan (2007). Journal
of Child Neurology.
Gastrointestinal Dysfunction




bad digestion
pathologic alterations
in bowel flora
increased gut wall
permeability
lymphoid nodular
hyperplasia in ileum,
in some cases
GI abnormalities
Methylation deficits
Immunological Irregularities




Decreased resistance to infections
Increased tendency to autoimmune problems
Shift away from effective cellular function (TH1)
to antibody (TH2) response
Food sensitivities/allergies
Jyonouchi, H., et al. (2005).
Neuropsychobiology, 51:7785
Central Nervous
System



Altered sensitivity
Abnormal processing of sensory and expressive
information
Abnormal neurotransmitter functions
Brain inflammation
ASD
Control
Neurons in autistic child:
– larger than control
– normal in appearance
Kemper & Bauman, 1992
Bauman and Kemper, 2005
Extensive documentation of large
brains in autism



About 20% of young autistic
heads are “macrocephalic”
(> 97th %ile)
Most are above average in
volume.
This is an atypical brain size
distribution.


It has no precedent in the
literature.
Herbert, The Neuroscientist,
October 2005
References

Dementieva, Y.A. (2005)

Deutsch, C. K. (2003)

Courchesne, E. (2003)

Sparks, Friedman (2002)

Gillberg, C. (2002)

Alyward, E. H. (2002)

Courchesne, E. (2001)

Miles, J. H. (2001)

Fidler, D. J. (2000)

Fombonne, E. (1999)

Ghaziuddin, M. (1999)

Bailey, A. (1999)

Lainhart, J. E. (1997)

Rapin, I. (1996)

Davidovitch, M. (1996)

Woodhouse, W. (1996)

Piven, J. (1996)

Piven, J. (1995)

Bailey, A. (1993)

Bauman & Kemper (1985)
Oxidative Stress
Chauhan, A.; Chauhan, V.; Brown, W. T., and Cohen, I. Oxidative stress in autism:
increased lipid peroxidation and reduced serum levels of ceruloplasmin and
transferrin--the antioxidant proteins. Life Sci. 2004 Oct 8; 75(21):2539-49
Sogut, S.; Zoroglu, S. S.; Ozyurt, H.; Yilmaz, H. R.; Ozugurlu, F.; Sivasli, E.; Yetkin, O.; Yanik,
M.; Tutkun, H.; Savas, H. A.; Tarakcioglu, M., and Akyol, O. Changes in nitric oxide
levels and antioxidant enzyme activities may have a role in the pathophysiological
mechanisms involved in autism. Clin Chim Acta. 2003 May; 331(1-2):111-7.
Yorbik, O.; Sayal, A.; Akay, C.; Akbiyik, D. I., and Sohmen, T. Investigation of antioxidant
enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids.
2002 Nov; 67(5):341-3.
Zoroglu, S. S.; Armutcu, F.; Ozen, S.; Gurel, A.; Sivasli, E.; Yetkin, O., and Meram, I.
Increased oxidative stress and altered activities of erythrocyte free radical
scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci. 2004 Jun; 254(3):1437.
James, S. J.; Cutler, P.; Melnyk, S.; Jernigan, S.; Janak, L.; Gaylor, D. W., and Neubrander, J. A.
Metabolic biomarkers of increased oxidative stress and impaired methylation
capacity in children with autism. Am J Clin Nutr. 2004 Dec; 80(6)1611-7.
Other patterns of abnormalities







Biochemical peculiarities
nutritional deficits
increased sensitivity to
toxins
problems creating DNA
building blocks
abnormal levels of sulfur
abnormal amino acids
impaired detoxification
Autism as systemic dysfunction
GI dysfunction
Methylation deficits
Immune dysregulation
CNS dysfunction
Inflammation
Oxidative stress
All of these areas represent “in points” for our research
into cause and potentially effective treatments.
SABRI: Who are we?
Members are from the disciplines of :
 Clinical Psychology
 The Brain Sciences Institute
 Biomedical Science
•
•
•
•
•
We have the right people and the most modern and extensive biomedical
laboratory facilities
We have institutional-level support for the initiative
We have the necessary relationships with external institutions to facilitate
collaborative research
And we are also parents, aunts, uncles, cousins and friends of Autistic children,
professionally and personally invested in this area.
We are determined to make a difference.
Thank you.