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The Locus Coeruleus and autism

Posted Apr 09 2009 7:16pm
I just thought that I would have to comment on the new study that implicates the area of the brain known as the locus coeruleus with autism. The locus coeruleus is the source in the brain of the neurotransmitter norepinephrine. The hypothesis originates from the fact that there is anecdotal evidence that when autistic children get fevers this mitigates their symptoms. The locus coeruleus is involved in fever. The authors go on to speculate that autism could just be due to dysregulation of the locus coeruleus and because of this it could make it easier to mitigate the symptoms of autism or possibly even find a way to reverse it. I have only read the article in science daily that I have linked to and the abstract of the study, so I can't comment on all of the specifics of the study. From what I have read though it sounds more like a hypothesis than the authors having any empirical evidence that the LC plays any role in autism. So, I won't hold my breath as far as any major breakthroughs in the treatment of autism as a result of this research. However, when reading things like this, it helps to give hope that someday, something can be done to mitigate or cure this horrible tragedy that afflicts so many persons. The authors go on to emphasize in the article that this does not mean something can be done for autism as a result of their research in one fell swoop (their words).

If the prevalence of autism is really 1 in 150, then if this becomes more than a hypothesis and further research validates this as something that could help autism, then this would provide an incentive for drug companies to come up with some norepinephrine agonist (a drug that will create more norepinephrine in the brain presuming autism is caused by a dysregulation of this neurotransmitter) and much money would be made and autism at the very least would be as treatable as schizophrenia is currently with anti-psychotic medications even if the medications don't cure autism. This might make ABA as a therapy for autism just as obsolete as hydrotherapy is now for schizophrenia. Hydrotherapy was the treatment of choice for schizophrenia in the 1940s before anti-psychotic medications were developed and used for schizophrenics. Like ABA, its proponents touted hydrotherapy as the only scientifically proven treatment to ameliorate schizophrenia. I realize that these are just dreams now and it is unlikely such a medication or treatment for autism will be invented based on this research in the foreseeable future.

I have emailed the lead author of the study Dr. Mehler and have asked him for a .pdf copy of the actual study itself so I will have more to read than just the science daily article and the abstract. If I get the actual paper I may edit this post or post a follow-up post.

What is most interesting of all to me is that about 20 years ago, when I had my first MRI scan by Eric Courchesne's research group, I had a similar speculation that the etiology of autism might be caused by a dysfunction in the locus coeruleus and that norepinephrine might be involved in the etiology of autism. The dorsal tegmental bundle is a tract that comes from the locus coeruleus and is one of the two main tracts of neurons that spreads the neurotransmitter norepinephrine to the various areas of the brain that use this substance to generate chemical messages that control various functions of the brain. The axons of these fibers project to the neocortex, hippocampus and cerebellar cortex and medulla. The cerebellum has been implicated in autism and various studies have shown a loss of purkinje cells in the cerebellum of autistics as opposed to normal controls. Norepinephrine is one of the two neurotransmitters that are used by purkinje cells The other one is GABA (gamma amino butyric acid). Norepinephrine acts as an inhibitory neurotransmitter. This might be the reason for the inability to control certain movements in autism and "stimming", lack of an inhibitory neurotransmitter. More evidence of the norepinephrine/stimming theory comes from the fact that some of the axons of the dorsal tegmental bundle terminate on the superior cerebellar peduncle, which is one of the three structures that attach the cerebellum to the rest of the brain. It has been found that stimulation of the superior cerebellar peduncles is reinforcing. Subsequent studies have found ablation of the locus coereulus did not abolish this reinforcing effect. I think it is possible that norepinephrine in the typical brain acts as an inhibitory neurotransmitter and suppresses certain things in the superior cerebellar peduncle. If this system was dysregulated it could cause lack of inhibition causing autistics to self-stimulate in order to get this reinforcement.

As I mentioned before, these fibers also travel through the hippocampus. This brain structure is responsible for short term memory. Persons who have had severe epileptic seizures have sometimes had this brain structure removed. These persons can no longer form short term memories and they constantly live in the past. I wrote a short story that was inspired by this phenomena.

Various studies have found abnormalities in the limbic systems of persons with autism. The hippocampus is part of the limbic system. Also persons with autism often have extremely good memories. Some of them are even savants with photographic memories. It is possible that the lack of an inhibitory neurotransmitter such as norepinephrine could produce this effect, opening up structures that would be normally inhibited in a typical brain.

I discussed this theory with Eric Courchesne at the time I was his research subject and he said it was an interesting theory that could possibly be valid, but only science would be able to tell. I wondered if it would be possible to do an MRI scan of the cerebellar peduncles the way he had scanned the cerebellum and had found abnormalities in the cerebellar vermi of persons with autism. He stated that such a study could not be done because the cerebellar peduncles were only a few millimeters and too small to be measured with MRI scanning and compared to typical controls. Of course this was many years ago and things may have changed so it might be possible to do a structural MRI of this area of the brain now. Of course, most studies nowadays seem to be doing functional MRI rather than structural.

I wrote to Margaret Bauman, another autism researcher, and asked her if there was evidence of abnormalities in norepinephrine in autistic brains. She stated that her research had not found any but it was possibly due to the measurement techniques they used.

Dr. Bauman is one of the few persons to have done post mortem autopsies of the brains of persons with autism. It would be good if post mortem autopsies could be done but the problem is autistics usually live out their natural lives and it has been only recently that persons have been diagnosed as autistic. This does not mean that autistics over the age of 75 do not exist as the mercury militia and others insist, but only that they were never diagnosed. If such persons near the end of their life could be found and will their brains to science, then perhaps we could find some real answers to autism and possibly even a cure someday. Of course I realize this is not realistic anytime in the foreseeable future.
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