Download AUTISM: WHAT WE DON*T KNOW

4 Unanswered Questions
in Autism Research
Dr. Lynn Waterhouse
The College of New Jersey
Presented at the
14th DUTCH NATIONAL AUTISM CONGRESS
March 21, 2014
‘sHertogenbosch, The Netherlands
Question 1:
What causes autism social impairment
to occur with restricted and repetitive
behaviors?
Brunsdon & Happé (2014) theorized
social impairment and
restricted and repetitive behaviors
are each separately caused
by
separate etiologies,
and
separate brain dysfunctions.
However, Brunsdon & Happé (2014)
are likely to be wrong
because autism has so many varied
causes
• There are 200 and 1,000 genes linked to
autism (Berg & Geschwind,2012),
• There are nearly 100 environment causes
(Grabruker, 2013; Maramara et al., 2014;
Schieve et al., 2014).
The known causes for autism
separately cause
different brain dysfunctions, and
each different brain dysfunction
causes
some form of social impairment
and
varied restricted and repetitive behaviors.
Gene X
Environmental
causes
Gene causes
Single or
multiple gene
variants
Father’s age
Environmental
causes
Valproate taken
by a Mother
Answer to Question 1:
Because the hundreds of different
causes for autism each cause
different brain dysfunctions
that cause both social impairment and
restricted and repetitive behaviors,
these diagnostic symptoms will vary,
and therefore the symptoms will not
be correlated in large samples.
Question 2:
How many different brain
dysfunctions cause autism?
Hundreds of varied brain dysfunctions
cause autism
Bigger brains
Smaller brains
Missing corpus callosum
Cerebellar impairment
Amygdala impairment
White matter impairment
Gray matter impairment
As well as
Neurotransmitter excess or deficit
Protein excess or deficit
One cause of larger heads and brains in
autism is the PTEN mutation
Rett syndrome in autism (right image)
causes smaller heads and brains
In some with autism
the corpus callosum is missing (left image)
Many different gene variants, such as
Noonan syndrome and Tuberous sclerosis
in autism cause maldevelopment of the
cerebellum
Abnormal amygdala size and function
affects some with autism
White matter underconnectivity
affects some with autism
The brain’s gray matter is denser in
some with autism (red line)
Answer to Question 2:
There are hundreds of
different patterns of brain dysfunction
found with autism,
thus all single brain dysfunction theories
of autism are wrong:
no single brain dysfunction is true for
autism.
Question 3:
Do risk factors for autism
cause many non-diagnostic behaviors?
Answer to Question 3:
Yes. For example,
the risk factor PTEN gene mutation
causes autism diagnostic symptoms and
non-diagnostic symptoms of epilepsy and an
atypically large head (Marchese et al., 2014)
Question 4:
Will most
idiopathic autism
(autism with no known cause)
be found to have a cause,
and thus become
syndromic autism?
Yes, evidence links syndromic autism and
idiopathic autism
For example,
4 genetically-linked syndromes,
each sometimes found with autism—
Neurofibromatosis type 1 (NF1)
Noonan syndrome
Costello syndrome
Cardio-facio-cutaneous syndrome
Are linked to other non-syndrome causes.
Answer to Question 4:
When we have discovered
the causes for autism,
all autism will have a known cause,
therefore,
idiopathic autism will not exist.
4 Conclusions
1. Autism symptoms should be studied
independently in relation to risk factors.
2. A catalogue of all brain dysfunctions found
with autism is needed to advance research.
3. Diagnostic and non-diagnostic symptoms
need to be explored together as caused by
individual risk factors.
4. Genetic research has demonstrated that the
division of idiopathic and syndromic autism is
unimportant.