The GUIDE: Autism Update

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When I started writing The Lab Rats Guide To The Brain, there was a plan to cover the basic brain areas, describe the structure of the brain and then the function of those areas.  Once the essentials were complete, I intended to discuss a number of neurological diseases and disorders in order to lend some guidance to use of conditions in writing.  Boy was I surprised when the focus of this blog became the diseases and disorders themselves, and much less about structure and function of the brain, not to mention the fictional writing aspects. Don't get me wrong, the intent was always to explain brain function in a manner that was hopefully better than trying to read textbooks or research papers. I'm rather pleased with how this blog has turned out, particularly when I get a chance to take things that I've learned professionally and update the information in The Guide.

Such is the case with today's blog. Last year I wrote a blog on Asperger's and Autism.  At that time I wrote:

 These days it seems that everyone is talking about Asperger's and Autism.  I'm sure that if you are reading this blog you have enough experience online to read comments by posters claiming Aspergers, and seen the web-based surveys that purport to tell you where you fall on a scale from Autism to Aspergers to "neurotypical" (i.e. the rest of us). 

... and went on to caution about the dangers of self-diagnosis.  To continue with the prior blog:

Autism and Asperger's are part of a spectrum of disorders characterized by a very poor connection with the outside world.  Autism is quite frequently co-diagnosed with hearing disorders - not deafness, but instead a hyper sensitivity to certain sounds.  Asperger's and Autism are well defined psychologically, but poorly defined neurologically.  In other words, it is hard to point to any one malfunctioning brain area.

This leads to misunderstanding, misdiagnoses, and misuse of the term.

Both Asperger's and Autism have characteristics that show up in scans of brain activity - low activity in the frontal areas, and high activity in occipital and parietal areas - in other words - a lot of sensory activity, but much less "executive function."  The exact cause is unknown, but theories regarding insufficient connectivity or hypoactivity abound.  There are a few things we do and do not know about the disorders.

Autism and Aspergers are part of a spectrum - at one end are highly impaired persons that do not interact at all with their surroundings - particularly not with other people.  At the other end is normal social functioning.  The actual description of this scale is "Autism Spectrum Disorder."  There can be individuals with ASD that are very bright, very high functioning in society. The only way we know a person might even have ASD is that they don't understand or even detect normal social cues. 

Again, there are many popular online web sites and emails that purport to tell you where you fall in the ASD spectrum on the basis of answers to a few (typically <50) questions.  SELF-DIAGNOSIS is DANGEROUS!   Not to mention notoriously inaccurate.  The professional neuropsychological exam that I have seen consists of over 300 questions, several story problems, an interval with a clinical psychologist, and extensive observation of social behavior.  Anything less is not a professional diagnosis.  A

Here's where the update comes in: Last week I attended a professional scientific seminar on several neurobiological characteristics that are considered "co-morbid" with autism. To update my previous comments on diagnosis of autism, there are three key observations that clinicians and scientists used to diagnose autism:

• impairment of social behavior
• impairment of communication
• a preference for repetitive patterns (also referred to as "issue of sameness")

Note:  A distinction that I did not make earlier between autism and Asperger's is in point two above.  a characteristic for diagnosis of autism is impairment of verbal and nonverbal communication skills.  Aperger's patients often develop normal verbal communication, while retaining the nonverbal communication deficits and other characteristics similar to autism. 

The severity of these above three characteristics places a patient on what is called the Autism Spectrum. Because there is variability in the characteristics and the severity, autism is more accurately a disorder, rather than a disease.  There are however many other characteristics that quite frequently are observed at the same time as the above three requirements. There is a high probability of gastrointestinal disturbances, and they likewise high probability of sensory abnormalities, particularly problems with integrating the different senses. While these latter conditions are quite frequently "co-morbid" with autism, they are usually inherited separately. Thus it is possible to inherit the G.I. disturbance or the sensory abnormality without inheriting autism and vice versa.

It is very important, however, to stress that what is inherited is the risk of developing an autism spectrum disorder, which does not necessarily imply that the cause of ASD is inherited. This is very important with respect to the new information that was presented in the seminar last week. One of the risks associated with sensory abnormalities, as well as ASD, is a long-range hypoconnectivity between neurons in different brain areas at the same time that there exists hyperconnectivity between neurons in the same brain area.

An important covariant with a diagnosis of autism is the prevalence of the gene MET.  [MET is the typical abbreviation used in genetics to define a gene or combination of genes with a common purpose, in this case MET controls the formation of connections between neurons.] Presence of the "at-risk" genotype (meaning simply that the gene is present) involving the MET gene, does not necessarily mean that the patient will show the ASD "phenotype" (the visible characteristics of the gene), but there is evidence that a high number of ASD patients do exhibit the at-risk MET genotype.  The result of this faulty gene appears to be neural circuits that are unable to produce an appropriate amount of inactivation between neurons. Inactivation or inhibition are important in a neural circuit, because they enable the circuit filter, tune or "shape" activity to fit appropriate patterns.  A neural circuit with abnormal conductivity can be considered very much like the "noise" and countered with poor radio reception, or in a crowded room with many conversations. A failure to appropriately "filter" sensory input is a common observation in autism spectrum disorders.

One of the important facts to understand about the MET gene is that it is only active for a short term after birth: a few days in rats, one month in monkeys, and likely less than five months in humans. While the connectivity disorder is not autism per se, it is a risk factor. However, that risk factor is only active for  a short time period before its effects become a permanent feature of the patients development. 

What this means is that the risk factors leading to ASD are established very early, making it highly unlikely that vaccinations given at ages of 12-24 months would have a significant effect on increasing the prevalence of autism.

In fact, despite the continuing alarms raised by certain celebrities and popular media, it is well-established that autism is not linked to childhood vaccinations.  There was one study which linked the mercury-containing preservative "thimerosal" with autism. We now know that even that data was inaccurate, even fraudulent (http://www.bmj.com/content/342/bmj.c7452).  The study was disproved, the journal in which it was published has retracted the finding and censured the author.  In addition, an article in the American Journal of Preventive Medicine, shows that the rise in Autism diagnoses predates the rise in mercury content of vaccines in California, and is parallel in Sweden and Denmark, countries with negligible Thimerosal/mercury exposure.

So, what are we to make of the new evidence that autism may very well be related to a failure to produce appropriate connections between neurons? Well, as stated right up front, autism is a spectrum of disorders, with relatively low and relatively high functionality associated with individuals. Understanding the genetic risks may allow identification of individuals likely to develop autism at a very early age, and as we better understand additional risks and causative factors, it may be possible to reduce or eliminate those for patients that are genetically at risk. Such manipulations may allow us as a society to "bias" the development toward high functioning ASD.  A better understanding of the neural connection disorder and normally developing (non-autistic) patients may also lead to better diagnosis and treatment of other neural diseases as well as a better understanding of neural development in general.

For more information on autism, ASD and related disorders such as Aspergers, I highly recommend the excellent resources at PubMed Health (http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002494/).