On the road to understanding autism (part 3)

This week I'll be taking a look at the chemicals associated with Autism Spectrum Disorder and summing up the article that I've been reading over the past three weeks (if you missed it the first two times, here's the link again!).  Let's jump right in to the discussion of neurochemicals...

One of the great things about looking at neurochemicals and autism is that here we have a real and true theory for what's occuring in ASD- the excitation/inhibition theory postulates that there is a lack of both local inhibition and long distance excitation in the developing brain that leads to the expression of autism.  Based on what we've already seen from exploring the overproduction of gray and white matter, the lack of minicolumnar structures and the changes in the different areas of the brain, this theory makes sense, but it's the underlying chemistry that really pulls everything together here.

The first area that researchers are really concentrating on are the glutamate/GABA chemical pathways.  Glutamate is the most abundant excitatory neurotransmitter in the body while GABA is used for inhibitory connections.  Glutamate is intricately involved in learning and memory through long term potentiation (which is a fancy way of saying that it helps with the "experience dependent plasticity" that I've been talking about for the past two weeks).  In patients with ASD, we see higher than normal concentrations of glutamate production, and decreased GABA receptors.  This partially explains why we see a lack of experience dependent plasticity in the brains of children with ASD.  If there is an abundance of glutamate in the system, then we will see a pattern of local excitation (going back to the excitation/inhibition theory), the local excitation will result in more synapses being upregulated in certain areas, while long distance connections are decreased or inhibited (because the connections in the minicolumns are disorganized due to the excess white matter).  All of this results in local circuits that are highly active and excitable (think repetative behaviors), and disconnection between areas that would normally overrule and inhibit local excitation (executive function of the frontal lobe).  

In addition to glutamate/GABA differences, researchers have also found that about 1/3 of patients diagnosed with ASD have increased levels of serotonin.  In normal development, the amount of serotonin in the system decreases as a child ages, but serotonin levels seem to be independent of age in the patients with ASD who demonstrate high serotonin levels.  Researchers have found that high serotonin levels have an effect on language learning, self-injuring behaviors, and IQ scores, but there has been no direct correlation demonstrated between amount of serotonin and degree of ASD symptoms.

One of the most interesting findings in the neurochemical arena comes not from the patients diagnosed with ASD, but from their families.  Parents and siblings of children diagnosed with ASD also demonstrate higher than normal glutamate and serotonin levels.  This truly shows how complex ASD is, "The Problem" cannot be simply described by looking at neurochemicals, genes, gray matter, white matter, or neuroanatomy.  In order to help people diagnosed with ASD we need to take a wholistic view and understand that it is the interaction of all these factors which result in the expression of ASD symptoms.  In order to effectively treat these symptoms, we need to understand the interaction and address the symptoms from their root cause.  Through exercises (both physical and mental) that directly challenge the functions of frontal and parietal lobes, the amygdala, the anterior cingulate, and the fusiform gyrus we may start to see progress in treating ASD.  Through activation of these areas, I would expect to see experience dependent modification of the gray and white matter both in the areas that are challenged, and those that used to be over active but recieve less stimulation due to the specificity of the challenge presented.  Perhaps the overproduction of glutamate and serotonin cannot be changed, but their effects on the system can be modified through the repetition of the challening stimulus.  In other words, we need to create an "artificially challenging" environment that supports experience dependent plasticity that will override the genetic and structural adaptations that the child with ASD has had in response to his "normal" environment.  THAT BEING SAID, I want to make it clear that I'm not saying that the parents are to blame for a child developing ASD, and I'm not saying that "The Problem" is purely genetic either- the "normal" environment that most kids grow up with is simply not enough, or the right, stimulation to override the natural tendencies of these particular children to develop ASD symptoms. 

Moral of the story...a combination of nature and nurture causes ASD to be expressed and a combination of nature and nurture can help these kids to lead a "normal" life.