UA-45667900-1

Thursday 17 August 2017

Viruses, Bacteria, Fungi, Parasites and Altered Gene Expression, Relevant to Autism






Today’s post started life as a review of how some viruses affect gene expression and may help cause, or just trigger flare-ups in, some neurological disorders ranging from autism to MS (multiple sclerosis). 
Some people with autism are treated with anti-viral drugs and, anecdotally, some do respond well.  This is not yet an area with hard facts and definitive clinical trials.  
It is actually better to first take a few steps back and consider how all microorganisms can play a role in human health by modifying the gene expression of the host (which is you).  There are four broad categories of microorganism.
Each type of microorganism can be countered by a matching category of pharmaceutical.

·        Antibacterials/antibiotics for bacteria

·        Antifungals to kill or prevent further growth of fungi

·        Antivirals to minimize (but often not eradicate) viruses

·        Antiparasitics to kill parasites  (protists)

All of the above categories of microorganism can affect the expression of multiple genes. By either up or down-regulating important genes at critical times during development, long lasting effects can be created, or there may be just transient effects.
Changes in gene expression likely play a role in many neurological conditions and in particular in what I call “flare-ups”, for example in autism, PANS, PANDAS and indeed schizophrenia.
Not all changes in gene expression are bad. The TSO parasites that do seem to help some people’s autism, by down regulating their immune response, very likely are modifying the host’s gene expression, which then reduces their immune response. This is the mechanism developed by the parasite to protect itself from the host (you) and ensure it is not eradicated.
Steroids affect the expression of multiple genes. When a bacteria of virus triggers PANDAS/PANS the positive effect of steroid therapy may well be by “resetting” the expression of certain important genes.  Here again, even though PANDAS/PANS is now treated clinically in the US, much remains unknown.
For those interested, earlier this summer revised treatment guidelines were published for PANDAS/PANS.

In "
Part I–Psychiatric and Behavioral Interventions," Margo Thienemann, MD, Stanford University and coauthors present consensus guidelines for treating the psychiatric and behavioral symptoms of children with PANS/PANDAS. Symptom improvement is aimed at decreasing suffering, improving functioning, and making it easier for the children to adhere to therapeutic interventions.

In "
Part II–Use of Immunomodulatory Therapies," Jennifer Frankovich, MD, and coauthors provide recommendations to help guide the use of therapies targeting the neuroinflammation and post-infectious autoimmunity that are common in PANS-PANDAS.

In “
Part III–Treatment and Prevention of Infections," Michael Cooperstock, MD, MPH, University of Missouri School of Medicine (Columbia) and coauthors representing the PANS PANDAS Consortium, present a consensus guideline for managing the infection components of these neuropsychiatric conditions.

There is research on what virus/bacteria affects which specific gene, but this area of science is in its infancy.
MS (Multiple Sclerosis) a condition that features faulty remyelination, is likely a much simpler condition than autism and yet nobody knows for sure what causes it. It has been suggested that a virus may be the trigger of at least some types of MS, but researchers are decades away from proving anything. So when it comes to microorganisms and autism, it is mainly a case of speculation and the odd N=1 case study. 

Viral triggers of multiple sclerosis 


The relationship between infections and autoimmune diseases is complex and the mechanisms by which infectious pathogens could trigger MS are likely dynamic, i.e., they might change over time and not be mutually exclusive. Epidemiological observations indicate that viral infections could contribute to MS development not only as triggers of disease exacerbations but also as etiological agents, i.e., long before the disease becomes clinically apparent. The two- to three-folds increased risk of developing MS among individuals with history of IM compared with subjects who acquired EBV without symptoms, the almost universal seropositivity for EBV in adults and children with MS, and the steep and monotonic increase in MS risk with increasing titers of antibodies to EBV in apparently healthy adults could suggest that EBV infection is causally linked to MS development. The mechanisms responsible for this association are far from understood. Moreover, the incidence of IM in Western countries (≥ 5%)  exceeds the prevalence of MS in comparable populations (0.1%) by far (more than 50-fold) suggesting that yet unidentified genetic and/or additional environmental factors determine whether symptomatic EBV infection indeed predisposes to MS.

Although one particular MS-causing agent might still be discovered, current data suggest that multiple infections along with noninfectious environmental factors trigger the development of MS. These factors are likely ubiquitous, i.e., highly prevalent in the general population, and they require a permissive genetic background that predisposes for MS development. Future studies investigating infectious pathogens in a complex and heterogenous disease such as MS will benefit from careful and detailed clinical, pathological, and neuroimaging-based patient characterizations and from reproducibility in different study populations. In addition, novel humanized animal models of autoimmune diseases that are simultaneously permissive for viral pathogens which usually infect only humans  should allow investigation of specific aspects of host–pathogen interactions during autoimmune CNS inflammation in vivo. The integration of these data might eventually allow us to better define the role of viruses in the etiology and pathogenesis of MS and how virus–host interactions could be targeted for MS therapy.  

The ubiquitous human herpesvirus 6 may play a critical role in impeding the brain's ability to repair itself in diseases like multiple sclerosis. These findings may help explain the differences in severity in symptoms that many people with the disease experience
What is still not fully understood is the relationship between the extent of the viral infection in the brain and the severity of diseases like multiple sclerosis and other demyelinating diseases such as leukodystrophies and Vanishing White Matter disease. For example, do the number of infected cells need to reach a certain threshold before OPC function is impeded? Are individuals who have congenital HHV6 more vulnerable to severe forms of these diseases?
"More research is needed to understand by which mechanisms the virus impedes the function of OPCs and what impact this has on the progression of these diseases," said Mayer-Proschel. "But it is clear that HHV6, while not necessarily the cause of demyelinating diseases, is limiting the ability of the brain to repair damage to myelin thereby potentially accelerating the progression of these diseases."  

Mainstream and “Alternative” Research  
Not all published research fits with the current mainstream scientific consensus. The mainstream is clearly moving towards the realization that all kinds of things can affect gene expression. One currently fashionable area is the gut microbiota, as in this article:-

Some researchers develop hypotheses that go much further, like this one regarding autism’s elder brother, schizophrenia.


Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

And this one by the same author:-

Herpes simplex virus 1 (HSV-1) can promote beta-amyloid deposition and tau phosphorylation, demyelination or cognitive deficits relevant to Alzheimer's disease or multiple sclerosis and to many neuropsychiatric disorders with which it has been implicated. A seroprevalence much higher than disease incidence has called into question any primary causal role. However, as also the case with risk-promoting polymorphisms (also present in control populations), any causal effects are likely to be conditional. During its life cycle, the virus binds to many proteins and modifies the expression of multiple genes creating a host/pathogen interactome involving 1347 host genes. This data set is heavily enriched in the susceptibility genes for multiple sclerosis (P = 1.3E-99) > Alzheimer's disease > schizophrenia > Parkinsonism > depression > bipolar disorder > childhood obesity > chronic fatigue > autism > and anorexia (P = 0.047) but not attention deficit hyperactivity disorder, a relationship maintained for genome-wide association study data sets in multiple sclerosis and Alzheimer's disease. Overlapping susceptibility gene/interactome data sets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies. In this way, the same pathogen could contribute to multiple diseases in a gene-dependent manner and condition the risk-promoting effects of the genes whose function it disrupts.

Back to Autism
As we have seen previously in this blog, autism is usually polygenic, meaning very many different genes are affected. This does not mean that anything is necessarily defective in those genes, it just means those genes are either over or under-expressed, this means you end up with either too much, or too little, of whatever that gene makes.
So for a polygenic condition, where in one person hundreds of your 22,000 individual genes are likely over or under-expressed, we really do not want anything to come along and further miss-express critical genes.
Many genes are inter-related and so miss-expression of one can trigger a wave of further effects. This can be either good or bad.
The science is still in its infancy, so it will be many decades before it is translated into medicine, but we can certainly already say what may be happening.
The interactome is a relatively new word to describe the whole set of molecular interactions in a particular cell.
 For example, the well-known bacteria H.pylori that can cause stomach ulcers:- 

Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome.

Just this one common bacterium affects half of the entire set of proteins expressed by a genome (the so called proteome).
So we should not be surprised if some bacteria or viruses have a bad, or indeed good, effect on autism.
This also bring us back to the idea of the holobiont and hologenome, which was introduced in an earlier post. The idea is that what really matters in human health is not just your genome, but the totality of what surrounds you, so that means everything living in you, on you and around you. That includes bugs, bacteria and also those of your pet dog.
All of these factors influence how your genes are expressed. During evolution your body has got used to things and if you make rapid changes, you may indeed upset the balance. So while chlorinating water may have an overall good effect, by killing all those bacteria your body had been expecting, there may be some negative effects. Humans evolved living close to animals, be it dogs or farm animals. We saw earlier that pregnant mothers who live with pets produce children with a lower incidence of asthma.
We also reviewed the hygiene hypothesis, which basically says that a bit of dirt is good for you.
So this post, rather than narrowing things down, really broadens them out.  Everything affects everything.  If you rock the evolutionary boat, don’t be surprised if strange things happen.
Taking Somali refugees to live in Sweden increased their incidence of autism. Is that really a surprise? Recall the Somali autism clusters in Sweden and San Diego.
Apparently, the Amish in the US have a low prevalence of autism. Is that really a surprise?  One reader recently suggested sending autistic people to live with the Amish, as a therapy. The possibly effective therapy would have been to send the parents to live with the Amish for a couple of years before the child was born.
So perhaps we should consider much autism, and indeed conditions like asthma, as collateral damage from modern living?  Life expectancy has risen, infant mortality has been greatly reduced, but the downside is that we now have much more autoimmune disease and that includes autism.

Autism and Microorganisms
Now back to autism and the four categories of microorganism.
Can parasites cause autism? Actually we know they can; for example cerebral malaria can result in it. But how often is this case? Probably very rarely.
Can fungi cause autism? Perhaps, but we know from many examples (including in the comments on this blog) that some fungi can make autism worse.  Is the fungus candida albicans growing in the intestines really an issue in most autism? I seriously doubt it, but oral thrush/candidiasis caused by inhaled steroids does seem to make autism worse and is reversible by removing the fungus. The effect seems more likely to be from the candida than the steroid, since inhaled steroids only mildly enter the bloodstream.
Can bacteria cause autism? Well streptococcus bacteria can cause OCD and cognitive impairment (PANDAS).
Can a virus cause autism? Antonio Persico, one of the more serious autism researchers, has suggested that some autism may be caused by polyomaviruses transmitted at conception from father to mother.
https://spectrumnews.org/news/could-a-virus-cause-autism/

Can the rubella virus cause autism? Some serious people do see a possibility, even in people who have been vaccinated.

These both remain controversial hypotheses; but can viruses cause flare ups in autism, later in life? This is also controversial, but I think quite plausible.  It all depends which genes the virus causes to get miss-expressed.
Enough is known to say that odd changes in autism may potentially be triggered by the appearance of specific types of microorganism, but quite possibly most microorganisms have little, or no, negative effect in most people. So it is not a case of all viruses/bacteria will make autism worse, but it is likely true that some may have the potential to do so.
In trying to figure out possible causes of autism flare-ups, due consideration should be given to microorganisms.  This is another case of personalized medicine, with all its potential pitfalls.
The big risk is potentially becoming obsessed with non-existing bacteria, viruses, fungi or parasites.  


Back to Antivirals and Autism 
Finally we come back to where the original idea for this post came from; is there any basis of the use of antiviral drugs to treat autism?
DAN-type doctors do prescribe the antiviral drugs Valtrex, Famvir or Acyclovir.


Antiviral drugs do not destroy their target virus they just inhibit its development.
Most of the antiviral drugs now available are designed to help deal with HIV, herpes viruses, the hepatitis B and C viruses, and influenza A and B viruses.
You identify a virus by looking for antibodies to that specific virus in the blood. You can test for antibodies that suggest if the infection is new and active, called IgM antibodies and you can test for antibodies that show the infection occurred sometime in the past, called IgG antibodies.
You would need to know which virus to test for, the common ones are:-

HSV 1:  Herpes Simplex Virus 1 causes canker sores in the mouth

HSV 2: Herpes Simplex Virus 2 causes genital herpes.

HHV 6: Human Herpes Virus 6 is commonly known as Roseola virus

EBV: Epstein-Barr Virus, causes the illness known as infectious mononucleosis

Measles

Rubella  


“We’re not saying that HSV-2 is responsible for infecting the [fetal] brain and causing autism,” stresses senior author Ian Lipkin, an infectious disease expert and epidemiologist at Columbia. Indeed, fetal infection with HSV-2 is so serious that it frequently leads to miscarriages or stillbirths. Rather, Lipkin suspects that HSV-2 is just one among many environmental insults that, when they arrive at a vulnerable point in fetal development in women predisposed to damaging reactions, may trigger ASD in the fetus.” 

Conclusion: Rate of contact with HSV1 and HSV2 assessed by the mean of detection of specific antibodies was similar between children with ASD and healthy controls.

Conclusion: Levels and seropositivity rate of antibodies to HHV-6 and HHV-8 do not differ between children with ASD and controls.
CONCLUSION: Titre and seropositivity rate of antibodies to CMV and EBV are similar between children with ASD and healthy controls.


Valtrex 
Valtrex seems to be the antiviral most commonly prescribed in autism.  This is an off-label use, meaning Valtrex is not approved to treat autism.  Valtrex is active against most species in the herpesvirus family. In descending order of activity:

So we might assume the people with autism who respond to Valtrex might have one of the above, or similar, viruses. Unless Valtrex has some other modes of action, unrelated to being an anti-viral, which remains a possibility. 

Mitochondrial Disease and Viral Infections
Since this post is already full of speculation, I will add some more. Some people say that their child’s mitochondrial disease was preceded by a viral infection, so how likely is it that a virus can trigger mitochondrial disease and then autism?  Again, this is not something anyone can prove, one way or the other, but it does look like your mitochondria are particularly vulnerable to viruses.
The virus will exploit the mitochondria to further its own development, perhaps in doing so, in some people with a pre-disposition, this triggers a process to chronic mitochondrial dysfunction.  Read the papers below for more on this subject.


Highlights


Mitochondrial dynamics influences mitochondrial and cellular functions.
Mitochondrial dynamics is affected during viral infections.
Viruses exploit mitochondrial dynamics and mitophagy to benefit infectious process.
Virus-altered mitochondrial dynamics determines the outcome of infection.
Disruption of mitochondrial dynamics promotes viral pathogenesis.

If a virus can trigger mitochondrial disease, as we have seen a vaccination can, is there any possible merit in using antivirals years later?
Is there merit treating regressive autism, which is likely to be mitochondrial disease, immediately with antiviral drugs?
Is there merit treating autism flare-ups, that do not respond to PANDAS/PANS therapies, with antiviral drugs?
Is there merit treating MS (multiple sclerosis) immediately on diagnosis with antiviral drugs? Would MS flare-ups respond to antivirals?

My take
If I was to develop MS tomorrow, given there is currently no cure, I think I might want to try an antiviral, just in case it might actually do some good.
My son with classic autism did have a PANDAS-like regression last year, with sudden onset OCD and strange verbalizations. It all went away after a couple of weeks, having been treated as a PANDAS flare-up, as documented in an old post on this blog. If after a viral infection he developed a sudden onset regression I would certainly reread this post.
Readers of this blog with a clear case of mitochondrial disease might want to check for the commonly implicated viruses, since if one was never suppressed this might be something to consider.
So do antivirals have a place in treating autism?  There is no hard evidence to support their use, but I would not at all be surprised if a minority do genuinely benefit. I think the most likely group might be those who have a sudden regression from near typical. As with PANDAS/PANS, the sooner the treatment commences, the better the likely outcome. 
Could antivirals help control flare-ups that can occur in those already with autism? They could well help; ideally you would confirm the presence of the virus first.   

Conclusion
I recently watched an expert clinician talking about irritable bowel syndrome (IBS); he was very open about his opinion that science likely only understands about 30% of the disorder. When it comes to autism I think science may be only at the 10% mark. As a result you have to be very careful about saying anything definitive.
We know that very many things contribute to the prevalence of autism.  It looks more than likely that viruses, bacteria, fungi and parasites may, on occasion, play a role in some people’s autism.
But, just like we know that in some people vaccination can trigger mitochondrial disease and result in an autism diagnosis, this does not mean it is a common cause of autism. Vaccinations have saved hundreds of millions of lives, but it has long been known that they can have side effects and that is why there is a large industry-funded compensation scheme in the US.
So while parasites can in some circumstances lead to autism, this does not mean feeding bleach to children with autism is a clever idea. Nor does filling them with antibiotics to treat a non-existing bacteria.
You can see why mainstream medicine is not eager to treat autism.
Nonetheless, applying that meagre sounding 10% of understanding can yield results, when applied with caution.










40 comments:

  1. Hi Peter and Tyler, I think my son has reached great stability, mad episodes and uncontrollable tics and or stereotypes are behind. My interventions are: Niagen, bcaas, 500 mg sodium valproate with lithium orotate 5mg and Grape fruit seed extract. 5 mg melatonin with valerian and passion flower and 50 mg 5HTP.No benzos or SSRI.On october I will add agmatine, gaba and or ashwawanda.He has fears af all kinds,specially to death,so his anxiety and ocd, even contolled, always will be an issue.Tried acyclovir 2 weeks ago but had a bad reaction, this means that virus is also an issue or not? His greatgrandfather died of MS,this is something that I should consider? Valentina

    ReplyDelete
    Replies
    1. My older mote severely autistic son just started school again and so far has done very well. Glad to hear his worst symptoms seem to be behind him.

      Delete
    2. Hello Peter,

      My son recently suffered a really bad viral epidode with chills and high fever and then developed a cold sore (herpes simplex are known to lie dormant and get activated when body is under duress). I remembered then that in the past too he had shown mild transient sores on his mouth and lips which I suspect have been herpes. As usual, our paed thinks its inconsequential as herpes simplex as we all know is self limiting. What do you think?

      I am also concerned about adrenal insufficiency or other endocrine imbalances as we had a major episode of painful urination which could not be ascribed to uti...we got the stool test and ultrasound done as well, and the symptoms resolved with alkasol. In a recent examination we detected mild hyperkalemia and hyponatremia in urine. It could mean nothing but when his bouts of frequent urination following stress, growth upregulation, an episode of painful urination, elevated potassium in urine and other such symptoms are laid out, there could be an indication for something to do with adrenal function, aldostrerone, thyroid, lactic acedemia...

      Have secured an appointment with an expert paediatric endocrinologist (boy, do they have a long waiting list) so maybe some information, at least, or maybe not. In this mysterious autism world, seek and ye should not find.

      If a picture paints a thousand words, then why cant lab tests do,
      for autism is hard to know and and the cause just never shows...

      Sounds pathetic!

      Delete
    3. Completely off topic but did you end your comment paraphrasing a Bread song?!

      Delete
    4. Valentina, a negative reaction to acyclovir might just mean he does not tolerate that drug, you need to ask a doctor. MS in the family could be a contributing factor, like so many other things. There are no firm conclusions to draw.

      Good news that your son is now doing well. Be cautious when changing your therapy, always go in small steps.

      Delete
    5. Anonymous,

      Oh you got it right!!!

      I wish and hope that my child can also one day experience the deep emotional impact of words and tune running together, hand in hand.

      I really hope so though I realize my motives are unsound and based on personal likes and dislikes and have no bearing on my child's well being....probably.

      Delete
    6. Thank you Peter, I will be carefull,I only will add Gaba and Agmatine,don´t know if I will be so lucky with agmatine. I forgot to mention that he is taking ALA in small amount,he is doing 300 mg but I could up to 600 mg,and LCarnitine.Valentina

      Delete
  2. Peter,

    To add on to my previous comment, blood serum levels for calcium, magnesium and bicarbonate ions were within range. KFT, LFT came out normal , chest x ray clean. I am pestering my doc to write up tests for metabolic panel....curious about lactate pyruvate and a CDSA. If nothing, I will have a base line data but our paed got cold feet and referred me to a neuro who can write, assess and if needed follow up on test results. So two appointments by this month and speaking up to two incredulous faces (endo and neuro) is impending. I absolutely hate this...when I told our paed that my son had started speaking out ' mama/ baba, toilet' after a month of oral mb 12 and three micro doses of folinic acid, his tone of voice changed to that of an adult indulging a fantasizing child...Really, in three days? He said. You have nothing to declare but your ignorance, I said (of course, in my mind).

    ReplyDelete
    Replies
    1. Kritika, a virus may or may not be relevant. You would think that if the autism symptoms get worse when the virus gets worse, it may indeed be connected.

      If the viral episodes do not cause autism to get worse than perhaps they are not relevant.

      Delete
    2. Peter,

      I agree but its so complicated. I have observed hightened irritability days before a viral strikes...could be true for all of us so I do not know. Once an acute illness sets in, my son is behaviorally in top form . But recently I saw something. My son has redeveloped an ocd...running from wall to wall, wall to switch board or switch board to switchboard with great determination sometimes doing some acrobatics en way. He is extremely joyful in his acions and on being asked what he thinks he is doing he will come and kiss me....I am here and doing something I like so please let me, he was communicating. Cute looking act but few years down the line the same act will look straight out from the 'cuckoo's nest'. It struck me then that following bumetanide last year he was showing the same great moves...but then he had a bad viral too at that time. So what is it? Was it the virus and not bumetanide that caused the behaviours last year too. Its very difficult to tease out cause and effect.

      Diggin deep for clues on higher ground!

      Delete
  3. Great post, it is a balancing act.

    ReplyDelete
  4. Tyler, Iam very happy that your son has started very well,surely will be a good school year. My son, that is here with me, wants to send you greetings.Valentina

    ReplyDelete
  5. Excellent post, Peter. Glad to see you covering this. I feel my son falls in to this autism autoimmune category. Makes using various interventions tricky. I think now I am at the point I have to analyze every intervention I try to make sure it is either not too much of an immune stimulant or too much of an immune suppressant. So many things on that list. I have read some research that vit E and fish oils are effective at not lowering or raising - pretty safe option. Trying that approach now. He is doing well. Also backed off the prophylactic use of antihistamines as I was concerned it could be affecting his immune system response - and is much better. Perhaps this is behind many kids' reactions to starting out ok with certain interventions and then things getting worse

    ReplyDelete
  6. yes, with MS amantadine medication which is actually an anti-viral is used to treat fatigue, by an "unknown mechanism"...

    ReplyDelete
  7. Off topic, but I would like to raise awareness for:

    https://phys.org/news/2017-07-ligand-half-life-peptides-minutes-days.html

    this was posted on reddit today and this could be huge, including for autism.

    Basically oxytocin lasts 10-15minutes in the blood, but with this new technique they might be able to make it last for days.

    ReplyDelete
    Replies
    1. The challenge for peptide using this approach is making it past the blood brain barrier as peptides tend to be small and simple and can more easily diffuse than a more complex molecule like the one suggested in this research which essentially tags the peptide such that the kidneys will more readily ignore it. In the article they discussed the use of oxytocin for inducting labor which is a peripheral effect of oxytocin rather than a central nervous system effect.

      Delete
    2. Well I have experience with the oxytocin nasal spray myself and did found it very calming and felt as if I was far less hostile towards unpredictable stress.
      The nasal spray has been shown to have positive results in some cases of autism especially those with low oxytocin levels.

      The problem with the intranasal spray is the short half life, not sure if it is possible that the nasal spray could have oxytocin attached to this peptide?

      Id be willing to guinea pig for it any given day.

      Delete
    3. I forgot to add, I have used chinese skullcap n the past before with quite alot of success, but had to discontinue it due to it increasing the amount of freckles I have.

      This is no surprise as chinese skullcap contains baicalin which is a prolyl endopeptidase inhibitor, it makes all peptides stay longer in the body, including oxytocin, but also alpha msh which i suspect is the reason for the increased amount of freckles on it.

      There seemed to be a buildup effect for me.
      The longer I took chinese skullcap the more pronounced the effects became.

      On top of that chinese skullcap has mixed gaba agonistic /antagonistic substances in it, one of which works similar to ritalin (methylphenidate).

      Combining chinese skullcap with oxytocin nasal spray might have a synergistic effect.
      I have not tried combining both at once myself yet.

      Delete
    4. Aspie1983,
      What exactly was the improvement you experienced with Chinese skull cap and and at what dosage? You say it is similar to Ritalin. Does it mean it improves attention? Reduces hyperactivity? I would very much like to improve my grand son's attention and awareness. When he pays attention he learns fast and it happens rarely. And were you always high functioning or after biomedical treatment. Thank you.

      Delete
    5. Hi salempea,

      I was taking around 4 capsules of swansons chinese skullcap a day which is a 4:1 extract 400mg a capsule.
      I found that it was great for me in accepting the situations that I was in, which have been a huge issue for me in always trying to predict the outcomes of situations with logic.

      Unfortunatly the effect does not last the entire day, it lasts about 3-4hours and the capsules are best taken on an empty stomach and in between meals.

      Ive always been high functioning and my experience with skullcap was good, but I discontinued it due to increasing the amount of freckles I have.

      If you want more information about chinese skullcap you can look it up on examine.com:
      https://examine.com/supplements/scutellaria-baicalensis/

      One the active ingredients in chinese skullcap is oroxylin A, this is the substance that improves attention.

      I found skullcap to improve my attention in a calm way, which probably is due to its mixed gaba agonist/antagonistic ingredients which is unique.

      I have to say, chinese skullcap has had some case reports of liver injury, you might want to look into that before you decide.

      All the best.

      Delete
    6. salempeacock,

      You might also want to look into cordyceps militaris which I am currently using, it is amazing for me.

      Delete
    7. Chinese skullcap contains oroxylin A, which is dopamine reuptake inhibitor (https://link.springer.com/article/10.1007/s12272-013-0009-6). It is the same action as ADHD stimulant medications such as Ritalin, Focalin, Adderall, as well as crystal meth. All these dopamine reuptake inhibitors carry and FDA warning of causing psychosis and schizophrenia (http://www.schizophrenia.com/sznews/archives/004802.html). If you are considering Chinese Skullcap for attention and learning, you might as well go for an ADHD drug to avoid many of other possibly undesirable effects of skullcap.

      V

      Delete
    8. Aspie1983, that's intriguing to me - chinese skullcap is also reported to help with histamine and stabilize mast cells. Also a study out there that it helps with itching symptoms for those with this as one of their histamine issues. I have tried it before with my son, but only given as a tea - I think I will give the capsules a try now. Interesting you mention in another post thread that mushrooms are helping you now - also a mas cell stabilizer. I may give the skullcap another try in capsule form, however for my son, seems best to rotate interevntions, or try them in pulsed cycles. Seems his immune system likes things much better that way.
      Thanks for sharing

      Delete
    9. I am surprised that some people here (Aspie1983 and other opponents of SSRI's) call SSRI's poisons while themselves taking dopamine reuptake inhibitors (DRI's) such as Chinese Skullcap. Let's talk about DRI's:
      1. They have the same action as known street drugs such as crystal meth and cocaine.
      2. Cause addiction and withdrawal symptoms. In fact, because of short lasting effect (a just a few hours), you child will show withdrawal effects later in the day, which manifest themselves as impulsivity, crankiness, snappiness, sleepiness. You get "Yosemite Sam" child. Read about side effects of Chinese Skullcap and ADHD drugs. Especially individual user reports.
      3. They can cause psychosis and schizophrenia (http://www.schizophrenia.com/sznews/archives/004802.html)
      4. They can cause seaizures and tremors
      5. They can lead to Parkinson's disease

      How's that for a poison? Feeding you child a low-dose street drug? Yeah, that is better than SSRI

      V

      Delete
    10. V,

      That was very useful....even I have read potentially dangerous effects of Scutellaria.

      I would be very cautious with herbs, mushrooms and other whole plant or plant based extracts and powder, especially if you have a minimally verbal or non verbal. Grape seed extract, aswagandha, brahmi...all made my son really uncomfortable. If you google side effects of these natural products one might become a little disillusioned...these are only as magical, benign or hazardous as any other supplement or drug.

      Big Conclusion: one man's ssri is another man's skullcap.

      Delete
    11. Skullcap has as I allready stated before, mixed gaba agonist/antagonist activity and DRI effects (due to it being a somewhat weak gaba antagonist).

      1. Yes it raises gaba and dopamine, so what, it does it on an intensity level of 1 compared to a 10 for meth on a scale of 1-10, you fail to see the bigger picture.

      2. Skullcap addicting, oh please dont make me laugh, I stopped it abruptly no side effects nothing, the binding capacity of skullcap is nowhere near your so called "ahummm "intelligent list of DRI side effects.

      3. Chronic use of dopaminergic type of drugs is bad, as is chronic use of any drugs, what are you even trying to proof.

      4. Skullcap is actually used AGAINST seizures, due its main effect being pro GABA.

      5. Drugs that work on dopamine are used against parkinson... chronic and IRRESPONSIBLE bombing of dopamine agonist can give parkinson like withdrawals yes, talking very very very high recreational doses for extended periods of time, which I would not exactly call a form of medication.

      As for all, balance in the key, you failed in making your statement, I wont even go down the path of comparing things like a tryptophan pill with MDMA induced neurotoxicity.

      Delete
    12. Thank you aspie1983. Exactly which area cordyceps militaris helps you and at what dosage? My grandson is three and a half years old. Our doctor prescribed oxytocin nasal spray for a month but it had no effect ( neither positive nor negative). He already is a very affectionate and cuddly type of boy at least with the family members. His main problems are attention and receptive and expressive language. He speaks a lot but all to himself.

      Delete
    13. @salempeacock Tue, 22 Aug 2017 19:16:37 EDT,

      Eventhough cordyceps militaris is natural and has a high savety profile even in high doses I would be hesitant to advice you using it allready for your grandson since he is still so young.

      You say he has mainly attention problems, please do note though that every kid is easily distracted, because they are exploring so much.

      However Im assuming you have posted this as you made the comparison with other kids his age?

      Anyway regarding myself, I find it helps me become more mentally calm, so I can choose on what I focus my mental energy on as a result of the calmness (not to confuse with dullness here).
      Where as without the cordyceps It seems I have problems (unwillingly) accepting the situations that I am in and am always anticipating what is going to happen next, which is partially I believe due my immunesystem workingi n overdrive 24/7.

      See it as a storm going on in my brain at baseline, I cant give my thoughts or emotions proper directions and try to solve everything with logic instead of on-the-go problem solving.

      I have been using realmushrooms cordyceps militaris powder, 2x 3grams a day, once upon awakening on empty stomach and the second dose around 2pm (2 hours after lunch).

      With regards to the oxytocin spray, I think alot of people have wrongly used it in the past, it actually requires some technique using it, if you just insufficate it the membranes in the nose cant absorb it.
      See youtube videos how to properly use nasalsprays.

      Delete
    14. Why don't you read first before answering, Aspie1983:

      ADHD Drugs Linked To Parkinson's Disease in New Study https://www.sott.net/article/224624-ADHD-Drugs-Linked-To-Parkinsons-Disease-in-New-Study

      https://link.springer.com/article/10.1007/s12272-013-0009-6 In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate [an ADHD drug component], a dopamine transporter blocker... Collectively, the present findings suggest that oroxylin A improves ADHD-like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported.

      https://livertox.nih.gov/Skullcap.htm Chinese skullcap .. may also have adverse effects on the liver. There have been several reports and small case series of acute liver injury with jaundice arising after 1 to 3 months of starting herbals or dietary supplements with Chinese skullcap (Scutellaria biacalensis), the liver injury resembling that associated with North American skullcap (Scutellaria lateriflora).

      Let's talk about Cordyceps. Enhancement of tyrosine hydroxylase expression by Cordyceps militaris https://link.springer.com/article/10.2478/s11535-010-0010-8 By inducing TH, Cordyceps increases dopamine production in the brain. A lead-poisoning warning: https://www.ncbi.nlm.nih.gov/pubmed/8854946

      >> Chronic use of dopaminergic type of drugs is bad, as is chronic use of any drugs, what are you even trying to proof.

      I am glad that you extended you criticism beyond SSRI's and included your favorite dopaminergic drugs. But I still don't get how you can view taking substances like Skullcap and Cordyceps, produced in facilities without regulations on purity and potency, often contaminated with liver and other toxins, safer than taking ADHD drugs which do the same function of raising dopamine through the same mechanism as Skullcap but cleanly.

      V

      Delete
  8. Hi everyone,

    So I've been doing my usual research and have found what I think may be a very interesting piece of the puzzle. Check out the following paper called "The possible link between the elevated serum levels of neurokinin A and anti-ribosomal P protein antibodies in children with autism"

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261830/

    When you read the above, clearly neurokinin A becomes very interesting, and so I've started to look at what can impact neurokinin A (assuming that reducing it would have a beneficial effect) and the first substance I've found is ... NAC.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260037/

    Now I haven't used NAC yet because it's quite sour, but I'm starting tomorrow. Of course, the anti-inflammatory properties (including inhibition of NKA) appear to require higher doses than that used for its antioxidant properties, but I'm wondering if the positive response in some may be due to NAC's anti-inflammatory (and maybe therefore anti-NKA activity) in those who have used higher doses.

    Anyone know the range of safe usage of NAC on a mg/kg basis?

    I'm going to keep looking for neurokinin A inhibitors, and if anyone finds something of interest in this regard, kindly share.

    Have a great night everyone,

    AJ

    ReplyDelete
  9. Tyler,my son´s godfather comes on sunday,fortunately, lightning trip.Should I start with agmatine in the high dose that would be for my son half a teasppon?His weight is 33 kg. Valentina

    ReplyDelete
  10. Well you can probably ramp it up pretty quickly, but since it has both acute and longer term effects on blood pressure due to its effects on adrenoreceptors, I would do a linear bump up to the 20mg/kg dose. Maybe do 1mg/kg more per day over 20 days so if there are any problems you know what dose. If you want to be super safe you can take blood pressure readings just as you might with bumetanide. I would not worry too much about it, but my experience is n=1 and I had frustrating results the first time around and then things were ironically much better with the higher dose.

    ReplyDelete
    Replies
    1. Sorry Tyler, don´t know if understood well,the correct dose would be 660 mg.I start with 33mg,second day 66mg,third day 99mg,fourth day 132mg and so on up to 660 mg that would be on the 20th day?.I will have it from Bulk,don´t know if I will be able to calculate the quantities correctly.
      Valentina

      Delete
    2. Yah something like that. If someone had died of agmatine sulphate overdose, then in the USA at least you would of heard it on the news as had happened with the ephedrine scare that caused it to be banned and it would be used as a strawman just as Picamilon was.

      Ironically, banning ephedrine likely caused 100s of thousands of deaths as the ECA stack containing ephedrine has really been the only safe pharmacological weight loss intervention to date and obesity arguably kills millions of people a year as well as increasing the risk of other societal problems like increased autism risk. A few people in poor health allegedly overdose on ephedrine with no autopsy done and Congress bans it immediately while at the same time subsidizing oxycontin usage because our Congress is owned by the pharmaceutical industry and will indirectly kill hundreds of thousands of its own citizens if it means enriching them and their families. I have heard Uruguay is far less corrupt and accountable to its people, but then again it is a small country with about 1/100th the population of the United States so it is like comparing apples to oranges.

      So to answer your question, I would use small measuring spoons used for adding small amounts of something until you get up to the desired amount. In the USA in addition to being world leaders in government corruption, we still don't use the metric system so just start out small and work your way up gradually. I would say just start off at the high dose except for your child already using other medications I have no idea if there might be some contraindication with.

      Delete
    3. Perfect Tyler, I was wondering if I could start off at the high dose, specially because you told me that low doses had the opposite result, but I will start as you said and see what happens. About my country, yes it is the least corrrupt of Latin America, but as you may know it is also the first country in the world to sell marijuana over the counter. Who knows,I think this is crazy. Valentina

      Delete
  11. Hi everyone,

    Yet another piece of the puzzle may be at hand. Check out this very interesting paper called "Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig"

    http://www.tandfonline.com/doi/full/10.1080/19490976.2017.1353849

    This is really interesting, and helps to explain (at least in part) the gut / brain axis in ASD.

    Have a wonderful night!

    AJ

    ReplyDelete
  12. Hi Tyler and Peter,
    I would love to try the BCAA therapy with my 23 yr old son, who is about 180 lbs. He takes pills which is a plus.
    I can't figure out optimal dosing for the BCAA as well as the niagen. Sounds like you use a scoop for your own son but my son is heavier and the scoop to capsule translation is confusing to me. I am thinking the agmatine Sulphate should be around 3 g. I am stumped regarding the other two.
    You reference apigenin at times. Is this another key part to this therapy?
    Thanks so much for your help.
    Nancy

    ReplyDelete
  13. Has anyone tried Valtrex? I just started my 13 year old son on it (very small dose and will increase gradually).
    First thing I noticed is lots of laughter. I read that it can stir up yeast in the gut which often leads to inappropriate laughter. I added in Biotin and probiotics which help with yeast and it stopped.
    I'm starting with 250mg (1/2 of a 500 mg pill). I wash off the blue dye because it contains aluminum which he just doesn't need. Just wondering if anyone else has had good/bad/no reaction to this drug.
    THANKS! Christine

    ReplyDelete
  14. Hi Peter, My daughter ( has ASD) also has igg antibodies for HHV6 and mycoplasma pneumoniae. She does have some underlying mitochondrial issues. She doesn’t have any obvious symptoms of these diseases. What is your take on this?…thank you

    ReplyDelete
    Replies
    1. The test shows that in the past your daughter was exposed to this type of pneumonia bacteria and the herpes virus 6. Neither need to be currently active diseases.

      This virus is very common and can periodically reactivate. HHV6A looks like the more troubling one for neurological conditions.

      If the herpes virus reactivates you could ask your doctor for treatment.

      Delete

Post a comment