Since there
is now interest in the potential benefit of probiotic bacteria to treat some
autism, I wanted to point out that there actually is a clinical trial underway
in Italy. It is funded the Italian Ministry of Health and by the Tuscany
Region. They use Vivomixx, an OTC probiotic
from the Italian speaking region of Switzerland.
Vivomixx
contains:
Streptococcus
thermophilus DSM
24731, bifidobacteria (B.
breve DSM
24732, B. longum DSM 24736, B.
infantis DSM
24737)
lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracaseiDSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734).
lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracaseiDSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734).
Before you start wondering, it is not cheap; the Swiss do not do cheap.
There is a detailed
explanation of the trial in the full version of the paper below. It is due to be completed at the end of 2017.
Vivomixx is virtually identical to a well known expensive probiotic called VCL#3, which has been used in research. Due to some dispute the originator of VCL#3 started a new company which now sells Vivomixx. In some countries one is available and in other countries it is the other one. VCL#3 is even more expensive.
Background
A high prevalence of
a variety of gastrointestinal (GI) symptoms is frequently reported in patients
with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be
linked to gut dysbiosis representing the observable phenotype of a “gut-brain
axis” disruption. The exploitation of strategies which can restore normal gut
microbiota and reduce the gut production and absorption of toxins, such as
probiotics addition/supplementation in a diet, may represent a
non-pharmacological option in the treatment of GI disturbances in ASD. The aim
of this randomized controlled trial is to determine the effects of
supplementation with a probiotic mixture (Vivomixx®) in ASD children not only
on specific GI symptoms, but also on the core deficits of the disorder, on cognitive
and language development, and on brain function and connectivity. An ancillary
aim is to evaluate possible effects of probiotic supplementation on urinary
concentrations of phthalates (chemical pollutants) which have been previously
linked to ASD.
Methods
A group of 100
preschoolers with ASD will be classified as belonging to a GI group or to a
Non-GI (NGI) group on the basis of a symptom severity index specific to GI
disorders. In order to obtain four arms, subjects belonging to the two groups
(GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or
with placebo for 6 months. All participants will be assessed at baseline,
after three months and after six months from baseline in order to evaluate the
possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3)
affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal
biomarkers related to abnormal intestinal function; (5) neurophysiological
patterns.
Discussion
The effects of
treatments with probiotics on children with ASD need to be evaluated through
rigorous controlled trials. Examining the impact of probiotics not only on
clinical but also on neurophysiological patterns, the current trial sets out to
provide new insights into the gut-brain connection in ASD patients. Moreover,
results could add information to the relationship between phthalates levels,
clinical features and neurophysiological patterns in ASD.
Trial registration
ClinicalTrials.gov
Identifier: NCT02708901. Retrospectively registered: March
4, 2016.
So in the coming years it looks like there will be some actual data with which you can decide whether or not to trial specific probiotic bacteria.
Hopefully, the Biogaia people in Sweden will provide their products for some independent researchers to trial on humans with autism, probably Swedish ones.
Peter, We used Vivomixx (VSL3#) for 20 days. We had the blue version with 450 billion bacteria, 10 sachets a packet, dissolved in water and kept refrigerated.It costs 22 euros a packet, discount price.
ReplyDeleteAs I said before, almost immediately, we noticed a striking behavioural change in terms of stereotypy. It was like the fever effect, he looked absolutely normal and he communicated with language in a conventially meaningful way.
We had no other obvious changes in his core symptoms, such as his lack of ability to inhibit intruding thoughts and flat to bad mood among others.
Then we had to go on short holidays with very high temperatures and it was inconvenient for me to preserve it.
Petra, now you can compare with Biogaia Gastrus and see how the effect differs.
DeleteSome probiotics are even sold to lower cholesterol and those ones should in theory be reducing inflammation, which is a trigger for the body to produce more cholesterol. At least it is easy to measure cholesterol.
Hi Petra,
DeleteCan I ask you what dosage you used for Vivomixx?
Thanks
Hi David R.
DeleteI used 1 sachet a day before breakfast.
Hi Petra,
DeleteWe did the 20 days trial and results are positive although I can't be 100% sure. He did 3 solid weeks at school, his teacher and therapists noticed it. Now we stopped giving him and after a few days I noticed a lot more stereotypy. In school they saw him more agitated as well. His therapy at the swimming pool went really badly today. On my second boy (N=2 in my case) I didn't notice anything different, but then again their "autism" is different.
I was wondering if you saw the same thing when you stopped it. And if so, are you giving him Vivomixx daily now?
Thanks
Hi David R.,
DeleteI don't use Vivomixx anymore because I am quite sure that it only rescued stereotypy in my son with no additional benefits.
Vivomixx made me become a believer in how much a probiotic can change behaviour and ever since I am willing to trial different commercial strains.
For the time being I don't want to address to stereotypy because things get complicated. I am sure that my son uses it as a means of relaxation and if he can't do that he becomes agitated. I can see that whenever on stereotypy he is processing information at the same time and I just don't want to deprive him of his means.
Maybe your son's stereotypy is due to something else and hope vivomixx works better for him.
Thank you for letting me know and good luck to you.
I don't know how long it will take them to send BG, as they promised. The thing that intrigues me about it, is that it promotes antiinflammatory effect through elevating oxytocin.
ReplyDeleteWhen I used Vivomixx I thought it would be perfect if I could have some oxytocin with it.
During our short holidays,I had Sytrinol and statins together with Verapamil and Baclofen. Baclofen helps with movement and probably with muscle inflammation. For Sytrinol I have no conclusion yet (both good and bad things happened). Statins helped him to get out of an extremely difficult build-up. By the way I've noticed that statins with Q10 is worse than statins alone(?).
Finally, although we had our issues, we've managed quite well.
There is certainly something happening with Biogaia Protectis, still I think he doesn't need more than 2-3 tablets. He gets dizzy with 5.
Don't know if you've seen this one:
ReplyDeletehttps://spectrumnews.org/news/single-microbe-may-restore-social-behaviors-in-mice/
Bets regards,
João Santos
This is very offtopic, but I was reading this paper on odor discrimination in mice that just came out yesterday:
ReplyDeletehttp://www.nature.com/ncomms/2016/160708/ncomms12043/full/ncomms12043.html
And what they did to impair odor discrimination was genetically block the production of the KCC2 protein so as to put the inhibitory cells needed for fine temporal control into a permanent state of excitation.
What I found interesting about this with respect to Bumetanide is that perhaps this same sort of test in those with autism could be employed to see whether they might benefit from bumetanide treatment, assuming that the KCC2 downregulation in classic autism is globally distributed throughout the brain.
Not sure about the practical methods of achieving this test in non-verbal and intellectually impaired people (would definitely take some trial and error) but these kind of "smell" tests are already used to detect Alzheimer's where the difference in ability to smell peanut butter between each nostril is compared to warrant a preliminary diagnosis.
The good thing about this test is if properly employed, parents would not need to literally wait decades for pediatricians to catch up to the latest and greatest science when it comes to autism screening and treatments, rather they could employ a "smell" test such as this to see whether it would make sense to put their child on a diuretic as it is unclear what percentage of the autistic population benefits from Bumetanide treatment (my suspicion is that it is high but this kind of test could give us some real answers).
Symprove in the UK are recruiting for an ASD study.
ReplyDeleteIan
That study is actually part of a PhD project, not conducted by Symprove, they are only supplying the product.
DeleteThis is very interesting, despite the outlandish title;
ReplyDeletehttps://www.newscientist.com/article/2095769-gut-bacteria-spotted-eating-brain-chemicals-for-the-first-time/
Nina
Something else offtopic, but definitely pertinent to a topic I know you have covered before regarding cinnamon:
ReplyDeletehttp://link.springer.com/article/10.1007%2Fs11481-016-9693-6
Basically, via cinnamon's metabolism to sodium benzoate, higher levels of GABAergic activity in the hippocampus (associated with poor learners) was reduced and caused the mice to improve their learning performance to that of fast learners while cinnamon treatment in fast learners had no effect one way or the other. Of course, this raises a lot of questions with regards to autism as hyperplasticity in various areas of the brain seems to be associated with autism, while learning itself is impaired because too many synapses is associated with memory not being consolidated, part of which means pruning unnecessary synapses. Of course I am just generalizing here, but perhaps cinnamon might be useful to counter broad acting GABAergics commonly prescribed for epilepsy and autism as the drugs used tend not to be very selective and often have the side effect of dumbing down individuals (or so that is how it is described be people who have used them for long-periods of time).
Hi Peter. Don't know how to contact you other than through this blog and thank you so much for it. My particular concern at the moment is not medication but rather tracking kids on the spectrum who go missing I believe that a universal approach is necessary but our local ( Melbourne Australia) ASD organisation Amaze is more bent on political correctness and conformance rather than practicality my personal view is that if our kids could be implanted with a chip that could be be registered on an app anyone with a smartphone could identify their location whist such an approach might be open to abuse it is better than nothing. I would appreciate it if your far reaching and obviously respected forum could raise this issue I am not sure if Monty goes wandering but so many kids on the spectrum do and it is a constant source of concern whilst there are any number of potential tracking devices on the market surely a universal approach would be of broader benefit
ReplyDeleteRFID chips are only very short range, and the technology as far as "embedding" them in humans is not desirable at this point due to the risks of tissue scarring and infection even though some people have done so already as self-proclaimed biohackers.
DeleteYour best bet is the same technology that is used here in the states to monitor parolees. I am not aware of any company that does this for autistic individuals, but I am sure there has to be a company out there that provides this service for senile individuals who can have wandering problems of their own.
I understand this concern because my kid is a wanderer. But most kids tracking devices today or work for close range with RFID or Bluetooth (more like to know if the kid trespasses a perimeter than to track her) or are GPS based and so are heavy and require frequent recharging and usually have monthly fees.
DeleteThe precision for both kinds is a little on the unreliable side, as low range options are vulnerable to physical barriers and give false alarm frequently, and do not pin point a direction. The GPS ones depends on energy source and a service provider. The fact that they are wearables makes them useless for us, as my kid takes everything but his clothes off, always.
My choice is to make sure my kid does not wanders, so fenced garden for us, and supervision. As he gets older and trickier I expect the measures will have to improve, but I prefer that to the risk of him leaving and we finding him too late to avoid harm (which can be seconds, after all the street is just there).
I would reconsider a device IF there was a perfect one: small, irremovable, reliable, precise and with long life. But it would still NOT be my main choice, because if you need tracking, things are already out of hand IMO.
Regards,
Jane.
That is why in the case where wandering is a problem, you need the kind of solution that is used to enforce house arrest for parolees (i.e. it tracks their every move and if you try and take it off, it alerts the authorities immediately). You could also easily gerryrig a cheap smartphone with a backup power source with the necessary protection to keep it from being damaged by water or a fall, and then have some sort of strap on the child at all times. That is what I would do if wandering was still a big problem with my kid. In effect, you need a real cellular solution and that probably means a well protected phone with backup battery power of some sort.
DeleteHi Tom's Dad, I am also in Melbourne. One of the boys in my son Morgan's class is a wanderer. His family have an assistance dog (labrador; a "failed" visual impairment trainee) that basically just sits down when the boy tries to wander off in public. Not a perfect solution for all situations obviously, but better than nothing for some.
DeleteAlso, you may be able to obtain funding for secure fencing from ... actually I don't know. Reluctantly I say, ask Amaze! I'm not mad about Amaze either - for example, one of their employees told me that the conclusion to be drawn from the sulforaphane trials was you simply have to eat more vegetables! So impracticable! And so so wrong! But I suppose they can only improve through feedback from their client group. Good luck - we have only occasional, close-by wandering, & that alone really is the stuff of nightmares. Alexandria
Since we are talking a lot about reducing excess cytokines, some interesting research to that effect recently came out with regards to vagus nerve stimulation:
ReplyDeletehttps://www.northwell.edu/about/news/breakthrough-first-human-study-shows-vagus-nerve-stimulation-significantly-reduces
This study is applicable to rheumatoid arthritis of which the cytokine profile is very similar to that of many people with autism (high IL-17).
Another very interesting study dealing with cytokines that came out and suggests interferon gamma directly affects social behaviors:
https://www.sciencedaily.com/releases/2016/07/160713143156.htm
The researchers also speculate briefly that this may all be part of the autism equation as a lot of evidence lately suggests that inflammation from the mother's immune system is trending towards the most likely cause of idiopathic autism.
Thanks for both those papers Tyler, very interesting to me personally. Regarding the second one: feeds into my amateur theory that part of the reason many people see a reduction in autistic behaviours when autists get high fevers is that the immune system has stopped attacking the body, & is instead attacking the infections like it is supposed to (sorry if this conclusion has been obvious to everybody else for ages). Alexandria
DeleteWas wondering if the settling down of autistic symptom during fever which I have observed in my son too could simply be a lack of energy that reduces hyperexcitability and dumbs down sensory stimuli a little. The same improvement in some autistic behaviour is seen after heavy bout of physical exercise ..although hormones are implied for this positive change. Could it simply be too low to be hyperstimulated.
DeleteWell there are many theories on what the "fever" effect actually is and why it helps some autistic behaviors. One intervention that was trialed in a study was to essentially put autistic people in a hot tub (or hot bath) to raise their core body temperature, thereby producing a fever effect in stimulating heat shock proteins that help protect cells from acute stress. I tried this in my son and the results seemed neutral so I stopped doing this. The other theory as you mention is that the immune system may be excessively downregulated in certain respects in autistic individuals and that a fever stimulates the immune system to normalize its activity. The research on this is inconclusive at best and there are various positions researchers have on whether the autistic immune system is hyperactive or hypoactive. I do think immune system dysregulation in the womb causes a cascade of developmental problems that later manifest as autistic symptoms down the road, especially when you have both autism and intellectual disability involved as a recent paper showed that specific maternal autoantibodies consistently popped up when you had autism and intellectual disability, but not just autism, or not just intellectual disability. The thinking here is that the maternal autoantibodies cause brain damage in the womb, especially in critical brain areas like the striatum/basal ganglia and cerebellum whose output is inhibitory in nature, so it could be that symptoms improve because the symptoms of fever apply a global dampener on brain activity (via inflammation) allowing the compromised inhibitory systems to not be overwhelmed (oh and BTW, the endpoints for the basal ganglia and cerebellum are the thalamus which does many things, including dampening excessive sensory input before passing it along to other parts of the brain.
DeleteBTW, here is a paper that just came out in the last week that discusses interferon gamma producing by T-cells in the meningeal tissue (the tissue just inside the skull, but outside the brain and therefore shielded from the blood brain barrier):
Deletehttp://www.nature.com/nature/journal/v535/n7612/full/nature18626.html
Even though the T-cells can't make it into the brain from the meningeal tissue, they found that the T-cells modulate their production of interferon gamma based upon social interaction. In effect, the idea is that if you are a more social animal, you should upregulate your immunity. Of course your immune system can do both good and bad things, plus it is very costly in terms of energy to maintain at heightened levels so an animal would want to be able to not waste any more energy than necessary on immunity than necessary. Now the more social an animal happens to be, the more likely it will be infected by pathogens from their social interaction. Conversely, organisms that are socially isolated will have no need for heightened immunity. Conversely, if you are getting sick from germs from other members of your species, then you are being social so what interferon gamma seems to do in this paper is also affect the interneuron GABAergic tone in the social areas of the brain thereby making the animal more social because if you are forced to share everyone's germs from communal living, you might as well be social so as to get along (aggressiveness or withdrawal in social species increases the likelihood of getting killed or ostracized).
So just a personal hypothesis here is that the fever effect might work through this mechanism in that a dysregulated and hypoactive immune system in those with autism is causing excessively low baseline levels of interferon gamma to be produced for whatever reason, causing the autistic person to be less social which causes less interferon gamma to be produced in some sort of vicious circle. This is just one paper, but ways to stimulate the immune system (more specifically interferon gamma) in a safe way (i.e. don't inject your child with flu virus every week) might help with some autistic symptoms. How to do that without serious side effects, I suppose is a question for the professionals.
The proposed evolutionary hypothesis linking dysegulated immune system to impaired socialization seems to be treading over different time scales . Are you saying that an abnormal immune system will not allow the individual to participate in normal socializations or that in asocial individuals immunity is not optimally developed because they are not coming across opportunities which trigger immune reactions leading to development of immunity which can turn him into a social being because he can participate in social gatherings without threatening his fitness. Are you implying evolutionary processes. Socialization is a complex phenomenon and probably a tangible output of numerous sensory and emotional processes acting in balance. As many parents will agree fever effect is not limited to increased socialization but also reduction in sensory overload and stereotypical behaviour which in a roundabout way will lead to better social interactions and awareness. Forgive me if I sound too simplistic but I feel sheer physiological exhaustion in wake of a fever..or strenuous physical activity resulting in what you called dampening of sensory stimuli, might also be a reasonable explanation of the fever effect. Yes, ultimately most autistic symptom, be it impaired speech, vision, cognition or hyper or hyposensitivities are impediments to normal socialization. As their is an adaptive disadvantage to asocial behaviour from a broader perspective optimal body functions including a healthy immune system should gear you up for healthy socializations.
DeleteHi,
ReplyDeleteAs mother to a 4.5 year old healthy joyous mildly/moderately autistic child, i wonder if anyone has observed physiological processes which seem to heal some autistic behaviours or cognition, a sort of self healing. My son was born healthy...apgar score 9, but displayed autistic symptoms basically in areas of deep bonding with primary caregivers although a generalized affection was there. Eighth month onwards these symptoms started fading and around one year my son started developing empathy imitation and speech..few words..milk mama..used a spoon. then around 1.5 years the brain could not handle it anymore and an mmr and flu shot probably addede to the crash and he was hospitalized with typhoid.He lost speech eye contact and even some of the motor skills. At the age of two years the healing started again..he stopped taking milk and for the first time slept through the night peacefully. Eye contact and engagement came back but the gap had widened too much by now and language comprehension and expression was non exhistent. Some sensory issues also started cropping up. Progress continues steadily but slowly..developing speech but social behaviour way off. The specific observation that i wanted to share is that about once in two months or so my son has a bout of diuresis..ten to fifteen times in two hours and of this is followed by a period of clear cognitive jump. What do you make of this. Self healing? Does it indicate possible benefit of bumetanide? Also..although no one believes in homeopathy here..a liver detox med Nat sulf gave us imitation in two weeks which opened up whole lot of possibilities. Should i try broccoli powder first. Please suggest. i truly feel that excluding autism arising from structural damage to brain most forms can be treated pharmacologically and not that much hardwired.
Many substances sold to "detox" are antioxidants and these should be helpful. A potent safe antioxidant is NAC and this is used by many people with autism. There are hundreds of other antioxidants.
DeleteA significant minority of very young children with autism make big improvements without any intervention, this is a kind of self repair.
Broccoli improves mood in some people, but not cognition. Bumetanide does improve cognition and overall makes you "less autistic" if you are in the 50% who respond to it.
So I would suggest NAC and bumetanide to start with. You would have a high chance of seeing an improvement.
Hi Peter.
DeletePlease advise if nac and bumetanide which I a suspect are going to give my son clear behavioural and cognitive improvements can be administered without professional help read doctor. I do have a doctorate in science so feel can safely pull it off. Been toying with the idea of bumetanide for the past one year but restrained by motto..first do no harm. And thanks for your blog ..you would not have an idea how much sensible help,a sense of controlband on an emotional note , hope it gives to parents
Both are very safe, but bumetanide is a prescription drug. NAC you can buy in any online supplement store. NAC is sold in cheap gelatine capsules, they work but if your child cannot swallow pills then you need to open them and NAC tastes bad. You can buy expensive NAC that comes in effervescent tablets, in the US it is called Pharmanac.
DeleteBumetanide works in a totally different way and is very effective in the 50% who are responders. My son has been taking it for nearly four years, will no side effects, just good cognitive enhancing effects.
Hi there, i am going to start my son on bumetanide and nac along with potassium and b vitamin supplementation which seems to be required while one is consuming these compounds.. Probably I will alternate periods of nac intake with carnosine and see if there is amy added benefit. Bumetanide is available online from British pharmacies. My son is not intellectually impaired, is toilet/potty trained and can write his alphabet and numbers. Buthis intellect is tainted with autism if you know what I mean..lack of imagination, limited reciprocity, default learning method being memorization. If I can decolor some of his autistic intellect and help him develop a little bit of what we all call a theory of mind he will be able to make it. So fingers crossed, ordering bumetanide and nac..will let you know how it goes.
DeleteHi Peter, a few concerns so please advise. My 4.5 year old mildly autistic symptom attends a mainstream school accompanied by an aide..not much learning takes place there and its more to develop social behaviour. For the learning part he goes to a remedial center where he is taught in ways most closely resembling approaches used for neurotypical kids but with lots of repetition.
DeleteIs there a fixed time period within which bumetanide induced diuresis takes place so that i can adjust the time of dosing to avoid frequent urination during school hours. And yes he responds pretty badly to acetaminophen so i have switched over to mefenamic acid or ibuprofen for the fevers. He will therefore probably respond positively to nac as you suggested.
But for me right now behavioural issues are not that much a concern as are his core autistic symptoms which were always there since birth..what i call the autistic gaze..the shifting eye movement that does not settle on people and the distant peaceful gaze .. although he was officially diagnosed only at 2.8 years as his active curiousity and periods of self recovery masked it from doctors. To me in this gaze which you can identify even in an infant is the hugest symptom of classic early onset autism.
As his intellect seems intact amelioration of any core symptom will lead to significant gains..please advise
The diuresis effect varies widely from person to person. In our case it is given at breakfast an hour before leaving for school. In that hour there are two visits to the toilet and then one visit at school before lunch. It is not disruptive, you just don't give it 5 minutes before leaving home.
DeleteYou just need to try it for a month, it should take at least ten days to take effect, so do not expect any immediate changes.
Kritika, a couple of years ago you said:
Delete"The specific observation that i wanted to share is that about once in two months or so my son has a bout of diuresis..ten to fifteen times in two hours and of this is followed by a period of clear cognitive jump."
I realise this is probably way too late, but perhaps this is still of interest, or is interesting to others. This sounds like a shift from burning glucose into ketosis, people will often dump a lot of water when this happens. The shift to using ketones could also explain the cognitive jump.
You might want to try a lower carb, moderate protein diet (or just less food and more exercise) to see if there is a response. One way to ease into this is to start by skipping breakfast or by using a no carb breakfast (e.g. based on eggs or cheese, or using healthy fats such as butter/ghee/olive or coconut oil). It's normal to shift from burning glucose to fats during the night, so by avoiding carbs at breakfast you can see if cognition is better while burning fat, and if it falls when carbs are eaten later in the day. (Perhaps this is why youngsters wake up very early, they run out of glucose and shift over into fat burning?!)
In a similar way any snacks between meals could be missed out or replaced with fat based alternatives.
Aspie2
Hi Peter,
ReplyDeleteWhile preparing to purchase PharmaNAC on-line I read that they revised their formula and it now includes Nurtasweet (sucralose) which has been linked to cancer and is just a garbage ingredient. People say the new formula tastes awful. Can you recommend another PURE pharma grade brand?
Thanks! Christine
We use fluimucil, which is made in Switzerland. I think PharmaNAC was originally made by the same company. Fluimucil is available in most countries except the US and UK. It tastes great. We now also use NAC Sustain and the cheap gelatine capsules, because swallowing pills is now easy. If you open the capsules and mix in a liquid it tastes really bad, but we did this for over a year.
DeleteHi Peter,
ReplyDeleteRelated question to NAC, we started seeing a DAN who asked us to stop NAC and use high dose vitamin C instead saying NAC can cause yeast. I remembered that u had said in the past there are several anti-oxidants, but NAC makes glutathione which crosses the blood brain barrier, where as vit c does not. In the US, there is also glutathione available, is glutathione use the same as NAC.
Thanks
BK
When I looked into this it was clear that most people believe that glutathione cannot be absorbed and that giving a precursor like NAC is the effective way to increase glutathione. Vitamin C and vitamin E are also good antioxidants and may well be helpful.
DeleteOfftopic, but I thought this might interest you:
ReplyDeletehttp://www.cell.com/neuron/abstract/S0896-6273(16)30310-5?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627316303105%3Fshowall%3Dtrue
Basically, the researchers showed how fear learning works in an area of the amygdala which is an area of the brain that many brain imaging studies relevant to autism suggest is highly disordered.
More specifically, they show that inputs as well as outputs of Parvalbumin Interneurons (these are all or nothing inhibitors when GABAergic plasticity is functioning correctly) are downregulated to associate fear with some contextual action. Normally, these cells prevent unwanted fears from popping up due to their inhibition of the fear circuit that links to a particular action (the memory is there, but it is constantly suppressed). When the PV interneurons have their synaptic connections downregulated, or else if they were hypothetically depolarizing (i.e. adding excitatory drive to a fear circuit due to irregularities in GABAergic plasticity), then you are going to have all kinds of crazy, albeit random types of fears pop up in behavior. In autism, the amygdala and the hippocampus are thought to be two of the most vulnerable regions to a leaky blood brain barrier and the inflammation that ensues. Inflammation of inhibitory neurons can cause them to be hyperexcited and alter chloride homeostasis, which of course can have a cascading effect eventually leading to temporal lobe epilepsy.
Since this paper shows a direct link between PV interneurons being taken out of the equation during successful fear learning, perhaps at least another psychological metric for successful use of autism drug therapies (i.e. so you know whether the therapy is objectively helping or not) is whether this exaggerated fear learning response remains in the person with autism after treatment. How a medical professional would ethically test that in a real live human being I guess is a good question. Perhaps something dealing with a simple auditory startle response that is also shown to be harmless long-term.
Again offtopic, but you have covered mGluR5 receptors before and this study on OCD I found very interesting and I am sure you will too:
ReplyDeletehttp://www.biologicalpsychiatryjournal.com/article/S0006-3223(16)32380-0/abstract
The dorsal striatum (also sometimes referred to as the caudate and putamen) has been thought for a long time to be ground zero for compulsive and repetitive behaviors as is the case in obsessive compulsive disorder. If there was no such thing as an autism diagnosis, then OCD in many people with autistic symptoms would be at the top of the list of alternative labels for autistic behavior.
What they found was that in mice that were genetically predisposed to OCD, they could instantly reverse OCD behaviors with an mGluR5 negative allosteric modulator. They also found that they could instantly cause the control mice to display OCD like behavior by injecting them with an mGluR5 positive allosteric modulator.
OCD behaviors are one of the biggest impediments to learning in those with autism as they distract attention from everything else (people, school work, metacognition such as personal reflection, etc.) and that therapy is a waste of time if the child won't disengage from those behaviors long enough to actually learn something.
What is exciting about this is that it suggests that perhaps one of the main pillars of autism, e.g. stereotypies and repetitive behavior (not exactly the same as OCD behavior but obviously related) might be mostly addressed with further research into this area. In the meantime, the question begs as to what kind of interventions may negatively modulate mGlur5 receptors, especially in the dorsolateral striatum.
Hi Peter, I recently stumbled upon this blog and am nw a regular reader...have observed so far tht you're not a fan of the 'natural' type of supplements like adaptogens, am I right? May I ask why...reason being I've used a range of adaptogens from Ashwagandha and holy basil to rhodiola and bacopa and moringa for adrenal stress for my kid...and they worked! Like magic...so was wondering if there's something wrong with their long term use or something...also, heard a couple of parents elsewhere raving about this other plant based product called Neural Balance with Anandanol...wondering if you have any thoughts on it...it's a bit pricey and I value your opinion now :) so thought I'd check...thanks. - BBM.
ReplyDeleteMany drugs are actually based on natural products and I have nothing against them. They just work best when they are standardized and you use just the substance within the natural product that produces the good effect.
DeleteMany supplements include multiple ingredients, like Anandanol. It might be of those 6 ingredients, one is good for your child, four do nothing and one is slightly negative. If you can find the one that really helps then you can save money and avoid the effects of the other ingredients.
Researchers believe that giving probiotics to healthy babies isn’t linked to any side effects. Kids that have a weakened immune system and pre-term babies are an exception.
ReplyDeleteIf you want to give your baby or child a probiotic supplement, talking to a physician prior to getting started will be a good idea.