The Biology of Autism: An introduction Associate Professor David W Austin, PhD Director: Swinburne...
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Transcript of The Biology of Autism: An introduction Associate Professor David W Austin, PhD Director: Swinburne...
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 TechnologyAustralia
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
• 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 emergence of a ‘new’ disorder
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
The genesis of the autism epidemic
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.
Example1. Schizophrenia: All subheadings, 39 pages2. 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
“decreased glutathione levels and increased oxidative stress may play a role in the pathology”
The brains of children with autism are experiencing severe oxidative stress and
inflammation
~ Kern & Jones (2006). Journal of Toxicology and
Environmental Health.
“The association between environmentally released mercury and special education rates were fully mediated by increased autism rates.”
Higher levels of environmental mercury are associated with higher
rates of autism
R2 = 0.97
0
50
100
150
200
250
100 150 200 250 300
Mercury Dose per Child (micrograms)
Pre
vale
nce
of
Au
tism
per
100
,000
C
hild
ren ~ Palmer et al
(2006). Health & Place.
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 nodularhyperplasia 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, 51:77-85
Central NervousSystem
Altered sensitivity Abnormal processing of sensory and
expressive information Abnormal neurotransmitter functions
Brain inflammation
Kemper & Bauman, 1992Bauman and Kemper, 2005
Neurons in autistic child:– larger than control– normal in appearance
ASD Control
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 StressChauhan, 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):143-7.
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.