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.