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Thursday, 16 January 2014

Matching Pathology with Behaviours in Autism


 
I think the wrong people are in charge of autism research; forensic scientists or even air-crash investigators might do much better.
We have seen in this blog that many drugs have a positive effect in specific types of autism. In many, but not all cases, the mechanism of that drug and its effect on the pathology of autism is understood. 
If you have followed an ABA programme, you will know that an experienced autism therapist would very easily be able to give a long list of behavioral issues that occur in varying combinations among her clients.
From reading the research, it is clear that the people who understand the biology, often do not understand the psychology and the behavioral issues they are trying to treat - but perhaps they should.  Only then can you target treatments for specific problems.  There can be no single drug for autism, but there can be a drug for obsessive behaviours, and another for self-injury.  You cannot say a low dose of X helps with social cognition, but for aggression you need a high dose of X.  To me at least, this is complete nonsense and shows a complete failure to understand the underlying psychology.
Just as most people struggle with all the jargon of biochemistry, I suppose the medical researchers fail to grasp the nuances of the psychologists’ jargon.  We need to match both sides, because we need science to solve a complex problem that presents itself in hard to describe, odd behaviours and not as nice neat equation to solve.
It is difficult to accurately describe and quantify the behavioral issues of a child with ASD.  It is very hard for a parent, but it is definitely possible for a psychologist using tools like ABBLS and others.  Then you can move towards seeing precisely what behavioral effects a drug has and stop expecting improvements in areas that are completely unrelated.
Having produced the list of deficit areas you can then try and understand the underlying pathology as to why a drug is effective.
I make no claims to have great expertise in this area, but it looks like nobody else does either.
Here are some examples:


Obsessions
Obsessive compulsive behaviours are well known to affect some people with autism.  This is a type of behaviour that most people would understand and would notice if they saw it, although they might find it hard to quantify.

Oxidative stress is a measurable pathological condition that is present in some people with autism.  Oxidative stress exists in other medical conditions and has a known therapy, an antioxidant like NAC.
By chance, it was found that treating someone with obsessive compulsive behaviours with NAC, greatly reduced those behaviours.

In the case of people with autism and obsessive compulsive behaviours, it would be good to know if other deficit areas were also impacted.  Clearly, taking away the obsessive compulsive behaviours, you would expect to see a general improvement, since the person is now much calmer and better able to function and so many behaviours should improve to a certain extent.  But does NAC reduce head banging and other SIB?  I think not.
So we can then conclude that oxidative stress triggers obsessive compulsive behaviours and NAC should be prescribed.  Oxidative stress may exist to a lesser degree in subjects that do not (yet) display obsessive behaviours.

 
Anxiety
I have not tried to treat anxiety in autism, but many people have.  Anxiety lies on the axis running from happy to depressed.  By raising the level of serotonin in the brain you move from depressed towards happy.  The antidepressant Prozac is given to many children with ASD to reduce anxiety. Prozac is a selective serotonin reuptake inhibitor (SSRI).

The problem with such drugs is their side effects and use can result in dependency.  If that was not the case, the advice would be simple.
I think a better and safer way exists to raise brain serotonin levels in autism.

Seizures and SIB
Not all people with SIB (Self-injurious Behavior) have seizures, but I expect many people with seizures have SIB.  Both conditions appear to be channelopathies (ion channel/transporter dysfunctions); but there is more to it than that, what triggers the channelopathy?  It would seem that in both cases the message comes via inflammatory signalling from the vagus nerve.  So to treat these conditions you can block the inflammatory signalling (vagus nerve stimulation), or you can treat the resulting ion channel/transporter dysfunction in the brain; doing both may be quite unnecessary.

If you have neither seizures nor SIB, then using any of the above therapies would be of little effect.

Many open questions remain
All is not clear; for example, where does hyperactivity fit in?  Where does anger fit in?  Is anger just a mild version of SIB?  It is extreme anxiety?  Is it something entirely different?

An interesting finding of mine was that showing affection appears to be pathologically related to self-confidence and lack of inhibition.  The pathology linking them appears to be neuroinflammation, or rather the control of it.

 
 

12 comments:

  1. Dear Peter,

    I agree that what you described. But many parents are expecting a treatment for the ‘core’. For example, in case of bumetanide, lowing intracellular Cl level in brain leads to more aware of the environment, this will lead to improvement in many areas in a portion of subjects. STX209 has also been reported to treatment the ‘core’ of Fragile X successfully in a small portion of subjects. -Yi

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    1. I am not convinced that the "core" of one child's autism is the same as the "core" of the others. This would explain why bumetanide and STX209 are not effective in all cases. Perhaps by lowering our expectations, we may actually achieve more, i.e. step by step improvements rather than "cure".

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  2. agreed,
    for me, I will see bumetanide is also treating one of the 'cores' of the diseases. [this also quoted in the sci web.]
    These treatment may not cure the disease, but lead to improvement in multiple-areas.
    like treatment of neuro-inflammation, I will see it as also treating the 'core'.

    others, will be symptoms management.

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  3. Hi Peter
    My 8yo with classic early onset autism suffers from terrible anxiety at times, and this leads to meltdowns. I have tried natural ways of boosting serotonin in the brain with little effect. I have been trying to implement your polypill step by step but the anxiety is getting in the way. I tried NAC and saw an immediate improvement - more affection, outgoing, willing to try new things but after a few days the effect disappeared. I supplemented with B vitamins but it didn't seem to have much effect. I tried bumetanide but stopped after one week as he was having panic attacks. I need to sort out the cause of the anxiety and panic attacks before I can try NAC and bumetanide again.
    I am hoping that verapamil could be helpful as he has year round dust mite allergies and food allergies. Another drug I have considered is propranolol. What are your thoughts with beta blockers for autism? Thanks.
    Nina

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    1. Propranolol is used by some people to treat anxiety in autism.

      I had several exchanges recently with a UK pediatrician who is treating people with Asperger's for anxiety using Baclofen. The majority of kids responded to the treatment. Baclofen acts on GABAb. We know that GABA is dysfunctional in autism and so this might be the root problem in your child causing the anxiety. So you might want to consider Baclofen as an alternative to the propranolol.

      If drugs stop working I suggest you read this post:-

      http://epiphanyasd.blogspot.com/2015/06/primary-and-secondary-dysfunctions-in.html

      I would also suggest you try Ibuprofen in advance of a stressful event and see if it prevents the meltdown happening. If it helps then this would help identify what is happening.

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    2. Thank you. I am convinced that dysfunctional GABA is the main cause of my son's type of autism. And this is exacerbated by high histamine levels and allergies. I have a fairly forward thinking paediatrician and he prescribed GABA twice a day, but I'm guessing just adding more GABA when it is already dysfunctional won't make any difference.

      I will look into Baclofen. If I can find something that will actually help him that would be amazing, and I might start to see his true self. I will also try ibuprofen in advance of stressful situations and see if that helps.
      Nina

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    3. GABA supposedly does not cross the blood brain barrier. So it should have no effect. Valproate does increase GABA within the brain.

      If the GABA receptors are dysfunctional, more GABA may make things worse.

      If he has the "standard" GABAa dysfunction, Bumetanide is the best therapy. Having switch GABA to inhibitory, increasing the level of GABA seems to actually help, but is not really necessary,

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    4. That's very interesting, thank you. I have been giving 2 x GABA a day and things have been worse. I will reassess my approach. Baclofen is definitely worth a try for anxiety, and I will look into bumetanide again once things have settled down.
      Nina

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  4. I went ahead with a trial of propranolol for my son's anxiety and for us it's been very positive. Because anxiety was such a big problem before, being able to treat it has lead to several other improvements.

    Interestingly, I think non selective beta blockers may be having a stabilising effect on potassium levels, which would be a good thing too.
    Nina

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    1. Nina, that is great news. What dose of propranolol are you using?

      It is interesting that it is also used to treat migraines and cluster headaches.

      Note that it does interact with Verapamil.

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    2. He is on a low dose of 20mg a day, given at breakfast time. After 1 hour you can clearly see the beneficial effect it's having.

      I've read that it interacts with both verapamil and bumetanide, so those drugs are out for us now.

      However, I did come across something quite fascinating. After perusing social anxiety boards, I discovered that a number of people (non-autistics) are combining propranolol and low dose clonazepam to good effect.
      Nina

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  5. Very interesting. Low dose clonazepam looks extremely safe.

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