Increasing Good Behaviors and Reducing Bad Behaviors in Autism

This blog is all about clever chemicals that can make life better for people with autism, but for several years I have also been learning all about behavioral therapy to achieve the same goal.  So I thought I should look for any lessons that I might apply from my earlier endeavours.  

Two of the best books in my ABA collection, based on feedback from all of our Assistants/Therapists/Friends are the oldest, and indeed the lightest.  They are more than 30 years old, as you might imagine from the front cover, which is a big turn off for many parents.

They are great books, that tell you what you actually want to know: how to get rid of horrible behaviours and how to encourage nice ones.

Dr Foxx is still going strong and won the 2013 Award for Distinguished Professional Contributions to Applied Research from the American Psychological Association. Foxx is a professor of psychology at Pennsylvania State Harrisburg and an adjunct professor of pediatrics at the Pennsylvania State University College of Medicine.

The thing I always found odd was why Dr. Foxx wrote two separate books, surely it is all the same subject matter.  He had his reasons.

Here is my parallel with my quest to develop a smart combination of safe drugs to help in autism. 

So far, most of what I have been doing is focused on decreasing the bad behaviors, so the blue part of the pill; the remaining work is find to ways to promote the good behaviors, the yellow part of the pill.

This might actually be more relevant that you realize.  While it is clear that bad behaviors in autism vary widely in both type and extent, desirable good behaviors should have much more in common.  We know that many individual drugs on the "blue side" are effective only in a minority of people, but perhaps there will be much more commonality on the "yellow side".  I expect this to be the case.

So my Polypill is taking colour, as well as shape.

Another good piece of news is that I found a precedent for orphan drug designation in classic autism.  It appears that in 1998 the FDA awarded orphan drug status to Naltrexone to treat childhood autism with SIB.  In the US, orphan drug status is only possible for rare diseases affecting less than 200,000 people.  There are other cases of orphan drugs in autism, but they are for rare genetic variants. Currently the FDA website for orphan drugs does not list Autism for Naltrexone.

Also, an interesting Australian drug NNZ-2566,  mentioned in a previous post, has recently been given orphan drug status in the US, this time based on Fragile X designation.  The drug is an analogue of IGF-1 and looks interesting to me.

If you want to see what orphan drug designation in the EU means, here is what Novartis received for its new Fragile X treatment, Mavoglurant.

Orphan drug status reduces the cost of approving a drug.  But how rare is classic autism, these days?

 

Promoting Speech in a 7 year old Non-verbal Child with Autism

I was recently asked if I would be happy to talk to the parents of a 7 year old non-verbal child with autism.  I agreed to share what I have learned so far from both behavioural interventions and more recently from drug therapy.  I decided that a dedicated post could also be very useful.

When Monty, now aged 10, was diagnosed with autism aged three and a half, he embarked on a home-based ABA programme, soon complemented by the use of PECS (Picture Exchange Communication System).  PECS is great, and when correctly implemented, clearly can work wonders.  Sadly, most people take shortcuts and just laminate a few pictures, stick them on the fridge and say they are “doing PECS”.

Click below to see short training videos:-

Phase 1 PECS

Phase 2 PECS

 

Once a non-verbal child has a communication system, be it PECS or sign language, then he/she can open up to the world.  Often speech then follows, but not always.

Monty learned to talk using ABA, PECS and special computer software.

With what I have since learned about the possibility of safe and effective drug therapy, I would do things slightly differently.  I would keep all the ABA and PECS and just add Bumetanide, NAC and Atorvastatin.  I can never know if Monty would have then spoken earlier, but I am pretty sure that would have been the effect.

 

Science based, not “Biomedical”, not Complimentary Medicine and not DAN!

Just in case you are wondering, my findings are based on reading the scientific literature on autism and its comorbidities.  I decide what research looks sound and what looks dubious; I draw my own conclusions.  “Biomedical” is a word that has been hijacked to apply to therapies that we would like to work, but usually lack a thorough grounding in science.  DAN seems to stand for trying everything, “Biomedical” and more.  Nonetheless, within the hundreds of DAN therapies are at least one or two that do stand up to scientific investigation.  

By applying a very blinkered view to the existing research, the Medical Establishment’s general view continues to be that autism is pretty much untreatable.  Having accepted this view myself for several years, I have learned that this view is fundamentally flawed; you just have to objectively follow the science and do a little research yourself.

 

7 years old and non-verbal

The longer a child remains non-verbal, the more challenging it becomes.  After a long period of time a child will just not see the point of changing.  It may cease to be a biological problem and become just a behavioural problem.

My combination of Bumetanide, NAC and Atorvastatin is as close as you can ever get with drugs to being risk free.  This has been a prerequisite of mine.  If after 7 years my child was non-verbal, I would probably be willing to take additional risks, but still nothing without clearly understood boundaries.

For the last few years we have had a little box in our kitchen drug cabinet marked “emergency asthma drug, one a half tablets”.  We have never had to actually use this drug.  The drug is Prednisone and it is for use when an acute asthma attack does not respond to the Ventolin “rescue” inhaler.  Prednisone is a corticosteroid, widely available, cheap and saves lives; but long term use can have major side effects. 

Prednisone lowers the body's immune system.  The science suggests that the overactive/damaged immune system in autism is a factor behind the autistic behaviours in children with ASD.  It would seem logical that temporarily lowering the immune system might trigger behavioral change in autsim, such as regaining lost speech or initiating it.  The most serious doctor I could find who is knowledgeable about this subject is Dr Michael Chez, of the Pediatric Neurology and Autism Neurodevelopmental Program, Sutter Neuroscience Institute in Sacramento California.

 

He wrote a paper I have already referred to in this blog called:-

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

In that paper he talks of his knowledge of the effects of prednisone on children with autism and he mentions the dosage used.

. Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week.  

Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner (Chez, unpublished data, personal communication).

In all, 17 of 32 patients showed response to prednisone after 2 to 4 months of  treatment (53%). Improvements were seen on EEG and  in language skills of the patients. Other steroid treatment series of regressed language in autistic spectrum patients diagnosed with LKS variant showed improved language with pulse-dose steroids.

Going to California is not an option for most people, but if I had a 7 year old non-verbal child with autism and ABA/PECS did not help initiate speech, then I would certainly read up on what he is suggesting.  I would still focus the time and effort on ABA/PECS and just hope that the drugs provide a little extra push.





 

Finished switching ears off!

I had another surprise a couple of days ago; I was standing with Monty outside the entrance to a very noisy ice-cream bar.  There were babies crying, a lady begging rather aggressively and an orderly queue to enter the shop.  Finally, the noise abated and I heard Monty say:-

“Finished switching ears off!”

Is there more to this than the emergence of spontaneous and appropriate speech?

Selective Hearing, Elective hearing and (S)elective mutism

I once did a course called Noise Control as part of my Engineering degree.  I recall that at the start of the course, the Professor confessed his desire to be able to turn his hearing on and off; clearly there were some noises he would prefer not to hear.

If you have children you will have discovered “selective hearing”; whenever you want them to come for a meal, they just do not seem to hear you.  If you offer ice cream though, they will hear the first time you call.

There is also the relatively common case of selective mutism, in people with anxiety disorders, they lose the ability to speak in stressful situations.

I think that many non-verbal autistic children probably have elective mutism; they just decide not to speak, or perhaps there is a barrier inside them that they just cannot get over.

Many people with autistic children initially go through a phase of thinking their child is deaf.  I know a child who lost his hearing and then a couple of years later regained it.  I met him just after his hearing was restored and I was convinced he had autism; he had all the characteristics.

Maybe some autistic children have elective deafness and/or elective mutism and perhaps a little pharmacological intervention could actually help them overcome this barrier?

For Monty, thankfully, these problems are in the past.  For him ABA and PECS did the job.

 

 

 

Neurogenesis & Neuroplasticity

Today we have two new N- words and we finally get to the bottom of what autism is and what it is not.   There is nothing revolutionary here, it can all be found in the research and indeed most of it can be found in just one book, but then who would read my blog?

We will start with the bad news and finish with the good news.

Neurogenesis

Neurogenesis sounds like a good thing; it is the birth of neurons in the brain.  This is substantially completed in the pre-natal period, but it can continue in certain parts of the brain throughout life.  After a head injury, or trauma, neurogenesis can take place.

In the case of autism the potential benefit exists, but seems likely to be minimal.

Many studies have already established the pattern of deformities in the autistic brain.  One researcher in particular, Eric Courchesne, seems to have chosen to make this his life’s work.  He has carried out repeated studies over many years focused on examination of brain growth, and overgrowth, in autism using post-mortem brains and later MRI (magnetic resonance imaging).
His findings are unequivocal, and in line with those of his peers.  In his autistic subjects, the brain grows much faster in the first couple of years than typical subjects and then the process slows right down and in later life the autistic brain starts to shrink.  His and other studies show that in later life the brain does seem to try to compensate for its defective development; this is seen as ineffective (but how can anyone possibly know?).

He finds a wide pattern of abnormalities, including the expected presence of a reduced number of Purkinje cells.  He goes on to argue that his evidence shows that this damage was done in the pre-natal period, so he will not be popular with the vaccine damage theorists.

“Thus, given the resulting tight bond between the olivary neurons and the Purkinje cells after this time, loss or damage to the cerebellar Purkinje cells results in an obligatory retrograde loss of olivary neurons. Since, in the autistic brain, the number of the olivary neurons is preserved, it is likely that whatever event resulted in the reduction of the Purkinje cells in these cases has to have occurred before this tight bond has been  established, and thus before 28–30 weeks gestation.”

 

“In addition, microscopic observations of enlarged cells in some brain regions in autistic children and small pale cells that are reduced in number in these same areas in adults strongly indicate changes with age. Clinically and pathologically, this process does not appear to a degenerative one and may reflect the brain’s attempt to compensate for its atypical circuitry over time.”

“This early cessation of growth results in a 2–4 year old autistic brain size that is not different from a normal adolescent or adult in the majority of cases. Thus, at the age of typical clinical diagnosis of the disorder (i.e. 3–4 years), the period of pathological growth and arrest has likely already passed, leaving clinicians and researchers with an outcome, rather than process, of pathology for study and treatment intervention.”

Here are three of Eric’s studies, which include graphs showing autistic brain development vs. the control group at various ages throughout life.

• When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports

• Unusual brain growth patterns in early life in patients with autistic disorder
• Brain growth across the life span in autism: age-specific changes in anatomical pathology.

Neuroplasticity

If neurogenesis was the bad news then neuroplasticity is certainly the good news. I think that Eric needs to read up on this subject and perk himself up.  It seems even a deformed brain can do some pretty clever stuff.

Neuroplasticity, also known as brain plasticity, refers to changes in neural pathways and synapses which are due to changes in behavior, environment and neural processes, as well as changes resulting from bodily injury.  Neuroplasticity has replaced the formerly-held position that the brain is a physiologically static organ, and explores how - and in which ways - the brain changes throughout life.

In the field of neuroplasticity we have some pioneering work from  Michael Merzenich is a neuroscientist. He has made some of "the most ambitious claims for the field - that brain exercises may be as useful as drugs to treat diseases as severe as schizophrenia - that plasticity exists from cradle to the grave, and that radical improvements in cognitive functioning - how we learn, think, perceive, and remember are possible even in the elderly."  Merzenich’s work was affected by a crucial discovery made by Hubel and Wiesel in their work with kittens. The experiment involved sewing one eye shut and recording the cortical brain maps. Hubel and Wiesel saw that the portion of the kitten’s brain associated with the shut eye was not idle, as expected. Instead, it processed visual information from the open eye. It was"… as though the brain didn’t want to waste any ‘cortical real estate’ and had found a way to rewire itself.

Merzenich created a plasticity-based computer aided learning programme called FastForWord, which  offers seven brain exercises to help with the language and learning deficits of dyslexia.

ABA and neuroplasticity.  Then of course, I started thinking about Monty’s  6 years of ABA and endless hours on his computer based learning programmes.  This of course is the link between neuroscience and ABA - the fuzzy science of neuroplasticity; otherwise known as making the most of what you’ve got. 

 

Conclusion

We have established that autistic behaviours are likely caused by stress and inflammation in the cerebellum, and in particular in the region of the Purkinje Cell Layer (PCL).

We have seen that in classic autism this stress and inflammation is associated with physical brain growth abnormalities that occurred in the pre-natal and early post natal period.  The oxidative stress and inflammation is ongoing throughout adulthood.

We have seen that stress and inflammation in the cerebellum can be caused by entirely different causes, that take effect later in life, such as Tuberous Sclerosis Complex (TSC).  There is another truly horrible one called Childhood Disintegrative Disorder (CDD).

With the availability of noninvasive MRI scans, it would be interesting and highly possible to ascertain the level of brain deformity in milder cases of autism and Asperger’s syndrome. 

Given that by the time autistic behaviors are exhibited, the damage to the brain  has already run its course, our main ally would seem to be neuroplasticity and of course to halt the ongoing oxidative stress and inflammation.

In addition, we need to consider countering the apparent ion-channel disfunction, and maybe give the damaged hippocampus a lesson or two about hormone production.

 

 

 

See you in Hell then.

Does religion have something to do with treating autism?  It should not have, but actually it does.

 

Depending on where you live in the world, you may come across a lot of religious intolerance.  In Iraq, Muslim Sunnis don’t seem to care for Muslim Shias, in the Indian subcontinent Hindus for Muslims, in Northern Ireland some Protestants for Catholics, the list goes on.  To an outsider, the differences between the competing teachings may seem marginal, but to an insider it can even be a reason to go to war.  It has often been the case that some of those going to these extremes, do not even really understand the competing teachings of their own religion.

 

What you might ask does this have to do with Autism and the subject of my blog?

 

If you have a child with autism, or you work full-time as a carer or therapist, you will likely have experienced emotional stresses that would destabilize all but the calmest of souls.  If you are new to the subject of autism you will probably skip over this part, if not, it will surely resonate deeply.

 

As will become apparent in forthcoming posts, this syndrome is very relevant when sifting through the research papers.  Acronyms are very popular in the literature of Applied Behavioural Analysis, neuroscience and psychiatry. Being a mixture of engineer/strategy consultant/PR consultant and aspiring entrepreneur I often struggle with spelling, let alone remembering what all the acronyms mean.  In this case, I will make an exception.  I will term it Autistic Stress Syndrome (ASS) and define it as when a sufferer loses all, or part of, their rational objectivity and becomes obsessive, close minded and  perhaps judgemental themselves.  A professional suffering from the syndrome will be lovingly termed “a smart ass”.  There are of course very many well intentioned smart asses and indeed some of the most useful people you can know will be smart asses.

 

This blog is all about science.  To be a good scientist you have to rational and objective.  To be a great scientist you also need to challenge accepted wisdom, realize that you do not (yet) know everything and sometimes you might just have got it wrong.

 

In the field of managing/teaching children with autism there are several schools of thought, some of which overlap.  Here is a short list:-

 

1.    Applied Behavioural Analysis (ABA) / Lovaas / Verbal Behaviour (VB)

2.    Floor time / Greenspan

3.    Hannen

4.    Occupational Therapy (OT)

5.    Picture Exchange Communication System (PECS)

6.    Speech  & language Therapy (SLT)

7.    Structure, Positive, Empathy, Low arousal, Links (SPELL)

8.    TEACCH

 

It is striking is that in many cases a professional specialized in one of these areas will not even want to discuss there being any merit whatsoever in the others.  As with religion, if you advocate a mix and match approach, rather than accept a one size fits all approach you will be consigned to purgatory or even hell.

 

When it comes to the field of Complementary and Alternative Medicine (CAM) the religious fervour grows even stronger and science goes completely out of the window.

 

 From my own biased experience of behavioural intereventions, here is what matters:-

 

·         Earliest possible start of intervention

·         Consistency 24/7 among care givers / therapists

·        Superhuman effort to provide near constant, stimulating, one-to-one contact during waking   hours for as a many years as it takes

 

I looked into all methods and found that the choice of ABA/ VB was a no brainer.  VB is just an approach within ABA that prioritizes speech.  PECS is a communication system for non-verbal kids, that is based on the principals of ABA.   Before the child is verbal, Hannen and Floor time are very useful approaches to encourage interaction. SPELL and TEACCH have lots of good methods highlighting the need to have structure, employ visual cues etc.  If the speech therapist (SLT) can teach you and your non-verbal child PECS that would be great.  Motor skills and play skills are a key part of an ABA/VB programme; they are also part of Occupational Therapy.  The OT therapist is probably using ABA without even knowing it.