Tuesday, February 4, 2014

Big News: A Breakthrough in Autism

Big, big news about autism from a very important article, published in Nature, by Wittkowski, et al. The open-access article (you can read it for free!) is a look at the genetics of autism both in terms of finding genetics patterns and in identifying the specific outcomes of those patterns. The authors describe origins of symptoms, cite risk factors, and make important recommendations for very early intervention both with drugs and with lifestyle changes. If you start on page 12 with the discussion, you can avoid the genetics discussions and get to the meat of the paper.
From Rockefeller University, the institute that showed that genes are structurally composed of DNA, comes a statistical approach to looking for the gene groupings that makeup autism. Instead of looking for individual genes shared by children with autism, as past studies have done, Wittkowski, et al, looked for groups of genes; and they did this in large population samples collected from other studies. Using their findings, they proposed a theory outlining the causes of autistic symptoms as well as suggesting drugs and other interventions that can ameliorate those symptoms.

To help identify the groups, they focused on children with epilepsy, a disorder with high co-morbidity with autism and the known problem of the calcium ion channels (which I will not go into here). They contrasted groups of children with and without autism and with particular etiology symptoms and severity of autism. Notably, they were able to pick out the population of children who appear to be developing normally, but who at 24 months begin to regress. They also picked out other sub-populations of autism. They were also able to map severity of symptoms with genetic makeup.

Their findings are consistent with the theory that "increased brain volume, brain connectivity, and skeletal growth correlate with severity of symptoms and suggest impaired inhibition of neuronal growth." They conclude that "ASD is in large part a neurodevelopmental disease ... with symptoms emerging gradually over the first 18 months of life.

Once they identified the gene clusters, they were able to identify the physiological issues and to formulate a theory about the causes of social symptoms of autism.

The authors point out that the very young child with autism is hyper-sensory sensitivity to urban sounds and the ever-present TV and is also  overwhelmed with too much social-stimulation from care-givers and preschools. That child is unable to process this rich sensory information and as a result, will avoid eye contact and social scenes. Wittkowski says that social avoidance "leads to underutilization of cortical regions responsible for language and social interaction, which are then pruned ("you don't use it - you lose it").

There is an informative flow chart of the process of accumulating symptoms that is worth viewing. It points out the risk factors and the methods for countering early symptoms and thus changing the outcomes of autism within the first two years of life.

Here are the authors' recommendations:
A shift in focus may be required from intervention in school aged children to early prevention (using medication) starting around 12 months of age, during which time children shape and refine their neural circuitry in response to social stimuli. ...although the American Academy of Pediatrics’ recommendation against television in children under the age of two years stems from studies in a more general population of children, unfavorable neurodevelopmental and behavioral outcomes in children with ASD might be even more compounded by early media exposure. Furthermore, early behavioral and educational interventions may need to favor personnel familiar to the child.
 Drugs that target ion channels may decrease hyper-excitation to a level where a child does not feel the need to withdraw from social interaction.
The bottom line of the article is we may be able to seriously change the outcomes of autism.
And as a reminder, here is a link to Autism Speaks' list of early signs of autism.) It is clear that we need to identify children VERY early. 
K M Wittkowski, V Sonakya, B Bigio, M K Tonn, F Shic, M Ascano, C Nasca, G Gold-Von Simson. A novel computational biostatistics approach implies impaired dephosphorylation of growth factor receptors as associated with severity of autism. Translational Psychiatry, 2014; 4 (1): e354


Knut said...

Dear Teresa,

congratulations for your summary of our article. It seems that we have been not clear enough to address the role of "pruning" (selective removal of neurons). Our hypothesis is that it is not "poor pruning" that inhibits social development, but that "avoid eye contact and social scenes" leads to underutilization of cortical regions responsible for language and social interaction, which are then pruned ("you don't use it - you lose it").
I hope this clarification helps.

Teresa said...

That makes it clear. I am excited about the changes that should come from this. We need to get the word out even louder about the need for early diagnosis and early intervention. And how exciting that meds could play such a crucial role in months or years to come.

Teresa said...

I updated the article based on the author's comments.