Comment by memossy | Hacker News Reader

Comment by memossy | Hacker News Reader

I quit a high flying job to research ASD when my son was diagnosed years ago and have read every single paper and website I could find.

My broad conclusion from this is that ASD is a condition caused by lots of different factors with common symptoms.

This makes treatments tough as ASD caused by oxidative stress would respond badly to treatments that work great on ASD caused by reductive stress for example (eg ASD symptoms that seem to get 'better' when taking paracetamol vs ASD made worse by it).

Thus when treatments are tried across the population you get odd results if you're not sub-dividing the groups into likely etiology, I've tried to look for statistically significant sets taking this into account.

The key dysfunctional system in most ASD seems to be the balance between the excitatory and inhibitory neurotransmitters GABA and Glutamate.

The two broad groups for this appear to reflect 'classical' autism, ie same from birth vs 'regressive' ASD, for example secondary to mitochondrial dysfunction where there is a sudden loss of ability.

For the former, a common cause appears to be GABA dysfunction, which the blog epiphanyasd.blogspot.com does a great job pulling together the research on.

In this case GABA doesn't flip to inhibitory from excitatory at birth and this could show up in brain scans for this subset of children with ASD..

The treatment options are interesting in this regard, but the 'safest' trial to check this dysfunction I've found is micro-dosage clonazepam (40mcg), which is already prescribed to children with anxiety (at 500-1000mcg doses). At this subclinical dosage, it should have no impact unless there is a dysfunction, but if it does (which it has in several families I know), then the research into other drugs that could treat this dysfunction becomes far more interesting (eg current trials in France by Ben Ari and Lemmonier on bumetanide).

That's really interesting, thanks for taking the time to share. I had no idea GABA's function in the brain 'inverts' at birth. When you say this could show up in brain scans, do you mean to say it has, or it's a theoretical (in the scientific sense of the word) explanation ?

I remember reading in 'The Brain the Changes Itself' that brain scan studies have observed that the brains of people with ASD do not differentiate between different auditory frequencies well. The way it is described in the book is that as infants develop, the part of the brain that processes sound starts to more selectively 'light up' as we 'learn' different frequencies, like someone becoming more precise when playing a single note on a piano-keyboard. However, it was apparently observed that the entire 'keyboard' lights up for people with ASD, regardless of the (audible) frequency.

I've always wondered about this. The author put forward an interesting theory about sensory over-stimulation in ASD sufferers, but it sounded kinda speculative to me. Did you come across this in your research? And if you did, do you think there's anything to?

That's interesting regarding auditory frequencies, especially in light of some comments by my autistic sister, who over the course of many arduous years of work by our mom became very high functioning. She leads a pretty normal life now (married, has a kid, works as an economist), but wrote the following:

"I don't remember much from before I could talk. The memories I do have are brief and disconnected from one another. I remember focusing intently on an object, such as a crayon or a piece of wire (you know mom, those twisties you use for the garbage) and being able to focus intently on that item, to the exclusion of everything else. I remember thinking that people could read my mind, thinking that they knew exactly what I wanted. I can even remember hearing and understanding some words but not understanding that they were an attempt to communicate. Hearing a sound from an air conditioning vent means the air conditioner is on, but it does not mean the air conditioner wants to engage me socially. It was not that I did not care about what they said, but rather that I did not know that they were trying to say anything to me. I vaguely recall interpreting human words, from family and teachers alike, in a similar manner. "

(from Triumphs in Early Autism Treatment )

Full disclosure - the mom mentioned above is also the founder of an Autism-related business; http://www.oaiautism.com/.

Thank you for story. My son diagnosed with autism at age two. Now he is 7, and practically did't speak (not counting simple phrases like 'give water, give pasta' etc..). Sorry for disturbing, but could you tell me (if it OK for you) at what age you sister start to understand / talk, and is there some 'aha!' moment maybe? And did you mom works only with ABA or some other method too? Sorry about my english.

Of course. I don't think she really spoke at all until age 4, and it was only with very, very intense behavioural therapy over the course of years that she made any progress at all. To give a sense of scale, my mother quit her job, got a master's degree in the field, and dedicated herself to it full-time (as in - her whole life; not just her whole professional life).

I don't recall a particular "aha" moment, but then, I'm only two years older than her, so I might simply not have been paying attention.

Part of the issue was that this was in the late 80's, and diagnoses were much, much less common then.

If you're curious, the book I referenced, which includes a chapter written by my mother, is at https://www.amazon.com/Triumphs-Early-Autism-Treatment-Cipan... .

You can find my email address if my profile if you'd like to contact me that way. Also, your English was good; you've no need to apologize.

That's something I can tangentially relate to: I have ADHD (diagnosed as an adult, which is rare), and it has a few common symptoms with ASD when it comes to (what others term) 'social deficits'. And I'm also an economist :) I guess the study of complex systems would have a natural attraction to people with an ASD.

In high school, I used to complain to my mum that I couldn't hear my school friends when we chatted on the bus home. So naturally she took me to have a hearing test. It turns out that I have unusually acute hearing (and this was confirmed later in life when I took another hearing test; when I came out of the booth the tech actually said to me 'I can't believe you heard some of those tones!').

In hindsight it's pretty obvious what was happening: I could hear my friends just fine but I couldn't comprehend what they were saying, probably due to the background noise and activity in the bus. In other words, it was an auditory processing deficit (which is fairly typical in ADHD sufferers). It's also interesting when you consider that around 50% of ADHD sufferers also stutter during their earlier years (I did).

The fact that one potentially effective treatment is 'delayed auditory feedback' (basically the stutter has a walkman-type thingie that records what they say and plays it back with a split-second delay), it's not too much of a leap to suppose stuttering might also be caused by an underlying auditory processing deficit (in this case, the processing of one's own speech).

I wonder if ASD and ADHD are related in some way, maybe sharing some common causes. I don't know what the current scientific thinking is, but I'm convinced that both are ultimately neurological disorders. Even the GABA-Glutamate theory is consistent with some other typical features of ADHD: super-high co-morbidity with anxiety/panic disorders and 'night-terrors' in early childhood (again, I had these and they were awful).

It feels like we're very close to understanding these conditions via direct observation of their (immediate) causes. Neuroimaging is getting cheaper and cheaper, and will eventually result in neurology and psychiatry merging into a single field. At that point we'll have practitioners capable of really understanding causes (neuro) and determining appropriate treatments (psychopharmachology, and maybe neuro-physical treatments).

I hope we reach that understanding soon; it appears the earlier the intervention the more positive the outcome.

You can see Dr Ben Ari's work on the flip here: http://www.sciencedirect.com/science/article/pii/S0306452214...

I was intrigued when my son had paradoxical reactions to GABA analogues so dug more into this (also has paradoxical reactions to benadryl, which is a different can of worms).

I think ASD, ADHD etc are all linked in terms of neurotransmitters and ion channel imbalance that causes overload on various pathways.

On interesting element on auditory processing is the similarities between ASD auditory sensitivity and hypokalemic sensory overload. Anecdotally I have seen dosing potassium reducing auditory sensitivity short term for possibly this reason.

Thanks for the link. I've read the first few pages: it's a really good read! Will definitely be reading this on the weekend.

On the paradoxical reaction to benadryl, and this is completely amateur speculation on my part, I wonder if it's because of benadryls anticholinergic effects (combined with a greater sensitivity, lower threshold etc.) resulting in a pseudo-anticholineric toxicity? And thereby outweighing the more typical effects of H1 anti-histamines? (disclaimer: I am very not a doctor, and this stuff is mostly beyond me)

It's due to CYP2D6 ultrarapid metabolisation.

The anticholinergic effects of benadryl have wider implications.

Wow, that's really interesting! I've been diagnosed with Asperger's, and went on clonazepam (and before, Ativan) and that really helped what I thought was anxiety. I mean, I did notice a direct benefit, and there's no reason to believe you over my doctor, but I'm always interested to alternative explanation as to why meds work.

Clonazepam in 'standard' doses has a very different effect to clonazepam in microdose, ie 1/50th of the clinical dose.

You can see this discussed by Dr Catterral here https://epiphanyasd.blogspot.co.uk/2015/08/low-dose-clonazep... based on the research he did supported by the excellent Simon's foundation (hedge fund manager behind Renaissance)

Above a 50mcg dose, the inhibitory effects disappear.

A nice explanation of why this happens can be found here: http://thelastpsychiatrist.com/2009/01/treating_insomnia_wit..., really interesting readable read

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