4 Unanswered Questions in Autism Research
Dr. Lynn WaterhouseThe College of New Jersey
Presented at the14th 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 autismseparately cause
different brain dysfunctions, andeach different brain dysfunction
causessome form of social impairment
andvaried restricted and repetitive behaviors.
VARIED &OVERLAPPING
brain dysfunctions Varied patterns of social
impairment & repetitive/restricted
behaviors
Gene causesSingle or
multiple gene variants
Gene X Environmental
causesFather’s age Environmental
causesValproate 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 brainsSmaller brainsMissing corpus callosumCerebellar impairmentAmygdala impairmentWhite matter impairmentGray matter impairment
As well asNeurotransmitter excess or deficitProtein 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 syndromeCostello 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.