Professional Documents
Culture Documents
A Brain Disorder?
Or a Disorder that
Affects the Brain?
Genes Inevitable
Prenatal Fixed
Brain Hardwired
Unchangeable
Hopeless
Modular, Static
Autism Model
Gene
AUTISM
Anomalies that
violate the static model
PERVASIVELY DYSREGULATED
BIOLOGICAL MECHANISMS
Molecular
and
Anatomy
Sensory
Signaling
Sleep
Sensorimotor
ii. Epilepsy
Somatic
Communi-
Social Behaviors
cation
Interaction
i.
After much gene hunting, genetics is
not explaining autism
5
Significant
IMGSAC B
4
IMGSAC B
3 Suggestive
1 “Critical level”
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X23 24
Chromosome
The environment is a VARIABLE, not
a CONSTANT
http://www.ewg.org/reports/bodyburden2
Status of Developmental Toxicity Testing
for the 2,863 Chemicals
Produced Above 1 million pounds/year
Some Data
On Developmental 0.4% 20-30 Tested for
Toxicity Neurodevelopmental
Toxicity
According to EPA
21.4% Guidelines
No Data
On Developmental This testing is
Toxicity NOT REQUIRED.
78.2%
To test these 2,863
chemicals in
combinations of 3
would require
85 BILLION tests.
In Harm’s Way, www.preventingharm.org
Texas autism rates, Potential association
by school districts between autism rates,
environmental mercury
other toxins in Texas
Palmer, et al., Health and Place, 12 (2006) 203–209
1990-1993 1998-2000
On average, for each 1000 lb of
Autism rates environmentally released
mercury, there was a 43%
increase in the rate of special
education services and a 61%
increase in the rate of autism.
Palmer et al. Health & Place 12 (2006) 203–209
genes •
•
gene expression
homeostasis
high frequency, low penetrance modulation • metabolism
• immune and inflammatory response
of vulnerability • hormone metabolism
http://www.niehs.nih.gov/envgenom/egp6.htm • nutrition
• oxidative metabolism and stress
• membrane pumps and/or drug resistance
• signal transduction
Neurotoxicology, 2006
Disproportionate
increase of white matter
(e.g. frontal lobe)
Herbert M. 2005
2.5
Autism-Language 2
Effect Sizes
Impairment Autism
1.5
Similarities: SLI
1
Effect Sizes
as high as 2 0.5
0
Total Brain Cerebral Total Frontal Parietal Temporal Occipital
Volume White Radiate Prefrontal Lobe Lobe Lobe Lobe
Matter WM
Dementieva 2005
Courchesne 2003
1.2
Volume Ratio
0.8
2-3 yo 7-11 yo 7-13 yo 12-16 yo
Marcel Just
Multispectral MRI Imaging
Inflammation and Oxidative Stress in Autism:
chronic, ongoing postnatal medical problems,
not confined to brain
Neuroglial activation and Oxidative stress in brain tissues
neuroinflammation in the brain of from autistic patients Increased
patients with autism concentration of isoprostanes
Vargas et al, 2005, Annals of Neurology
Vargas et al, 2005, Annals of Neurology
A B
• These changes were found
at similar intensities in
brain aged 5-44 years
• Greater intensity of
inflammation in a 3-year
C D old’s brain
Pardo: Astrogliosis in Radiate White Matter
Astrogliosis Microgliosis
GFAP HLA-Dr
Herbert:
Radiate White
Matter Enlargement
Pardo
GI, Immune and Metabolic problems
• 46-96% of autistic children have GI disease
• constipation, diarrhea, inflammatory bowel disease, abnormal
intestinal organisms
• 30-70% have immune abnormalities
• Allergy, recurrent infections, eczema, anti-self antibodies
• Many have methylation and/or mitochondrial problems
Eczema
“Intrinsic static
comorbidity” or treatable
medical condition?
Note distended abdomen,
skinny arms and legs
This will chronically
• Deplete nutrients
• Circulate substances to
body and brain
These can worsen brain and
body metabolic shortfalls
until treated
(Steve Kahler)
The “Blood-Brain Barrier” is
not an absolute barrier
Regression, Fluctuation and Improvement:
Beyond “static encephalopathy”
• Treatment-responsiveness
– Stable improvement can follow treatment
– Published reports of loss of diagnosis (Fein D –Sutera, Kelley JADD ’06,’07)
– Recovery documentation studies in process
Neurobiological Implications:
NEUROMODULATORS, not just wiring
MIGHT AUTISM HAVE A
COMPONENT OF TREATABLE
ENCEPHALOPATHY?
• Would correction of metabolic, immunological or
biochemical contributors to an increased
excitation/inhibition ratio improve level of
functioning?
• Clinical trials are underway and more are
needed.
Postnatal regression to autism
Folinic+Betaine
Metabolite Normal Range a Baseline Folinic+Betaine +methylB12
Methionine (µmol/L) > 24 1/8 5/8 7/8
SAM (nmol/L) > 80 2/8 8/8 8/8
SAH (nmol/L) < 23 2/8 7/8 7/8
SAM/SAH >4 1/8 7/8 7/8
Adenosine (µmol/L) < 0.3 4/8 8/8 8/8
Homocysteine (µmol/L) >5.5 3/8 8/8 8/8
Cysteine (µmol/L) >180 0/8 2/8 7/8
GSH (µmol/L) >5.4 0/8 2/8 7/8
GSSG (µmol/L) < 0.33 0/8 2/8 8/8
GSH/GSSG > 16 0/8 3/8 8/8
______________________________________________________________________
______
a Range estimated to include 90% of control children
James 2004
Before and After Treatment
IQ “60”
IQ 150
The emergence of a
new autism model
OR is it
Is autism a BRAIN
A DISORDER THAT
DISORDER?
AFFECTS THE BRAIN?
THE BRAIN IS WET!
and it’s attached to the
body!!!
It’s not just a computer.
Clinical
Implications of
Environmental
Toxicology for
Children’s
Neurodevelopm
ent in autism
Autism Society
of America
Special Issue of
Advocate on
Environmental
health and
Autism
December 2006
www.autism-society.org
Autism-Environment
CME Executive Summary
• Concerning increases in autism as well as allergies, asthma, learning
disabilities and other pediatric conditions, all suggest a contributory role for
environmental factors.
• Understanding mechanisms of environmental toxicology has the potential to
improve how we treat affected individuals.
• Autism can be reframed as a medical condition with features that affect the
whole body including the brain.
• Low dose, chronic and combined exposures can have significant impact on
neurodevelopment and children's health.
Gene
AUTISM
Gene Environment
To Systems
Epigenetics
PERVASIVELY DYSREGULATED
BIOLOGICAL MECHANISMS
Molecular
and
Anatomy
Sensory
Signaling
Sleep
Sensorimotor
ii. Epilepsy
Somatic
Communi-
Social Behaviors
cation
Interaction
i.
To a Gene Environment
Whole-Body Epigenetics
Understanding of
Autism
PERVASIVELY DYSREGULATED
BIOLOGICAL MECHANISMS
Molecular
and
Anatomy
Sensory
Signaling
Sleep
Sensorimotor
ii. Epilepsy
Somatic
Communi-
Social Behaviors
cation
Interaction
i.