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A Surprising Clue to Tourette Syndrome


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Hi Laurensmom & all!

 

I just posted this news over at the Tourette's forum & Chemar kindly directed me here!

I am very excited about this info, too, because the more I research the function of H3 receptors, the more I see an almost perfect clinical picture of my son's issues! Turns out that there are a number of both histamine (H3) agonists AND antagonists going thru research & development right now - for Alzheimer's & other cognitive disorders. This seems to be an issue for people with an attention deficit as well.

 

I have 5 kids - only my oldest (18yo ds) has Tourette's, but the others have food intolerances & some ADD/ADHD issues, too. (My 3rd child has issues that would qualify him for a PDD-NOS diagnosis if we went that route, but I had a dental amalgam replaced while I was 5mos pregnant with him & now that I have seen the research, I am convinced that was the source of his brain injury)

 

While the genetic disorder discussed here is believed to be rare, anything that throws a monkeywrench into the brain histamine pathway would theoretically have the potential to create a similar effect.

 

Since histidine requires a methyl group to be converted to histamine, that seems like a potential clue for whether a person's tics would be related to low brain histamine? My son's B6 & B12 levels are both low, though, & he has always had symptoms of both overmethylation & undermethylation so I've never been quite sure what to make of that.

 

I'm still digging trying to find out as much as I can about this stuff & hopefully make sense of it all. I'm still inclined to think that it's an autoimmune type disorder & I suspect that anything we can do to reduce reactivity or at least keep those histamine levels steady rather than fluctuating (similar to insulin in a type I diabetic) is bound to help minimize our kids' issues.

 

I will continue to watch this discussion with great interest & I also will add here anything more that I can find! Thanks so much for sharing your opinions, insights & experiences everyone! I am praying this will be the key that opens the door to a chance at a normal life for our kids!

 

~Grace

 

 

Ah ha! I think I found something of interest ... this conversation may explain the paradox Chemar and I discussed above?

 

http://www.prohealth.com/fibromyalgia/blog...l.cfm?id=731019

 

I have posted about this several times...taking histidine literally gave me my life back. I still have to take it every day to keep down the allergic responses (food, pollen, chemicals, etc) but the amount I take varies according to my total load.

 

The two brands I prefer are Montiff and Jo-Mar. You can find both on the internet. If you take histidine you do need about 15-20mg zinc for every 500mg of histidine.

 

Eddie, while high histamine can be a problem, especially in certain types of mental illness, there's a paradoxical effect in that the higher your blood levels of histidine, the slower the mast cells are to release histamines. For the conversion to take place it also requires zinc and B6, so for that reason I suggest that people keep their zinc levels adequate, but not high and avoid the histidine supplements that include B6 unless they are trying to use it to increase histamines (this is another topic, but it affects sexual function).

 

I have been using histidine for about 15 years now and even wrote a paper on it for my sports nutrition certification. It's an amazingly overlooked amino acid...many of my clients with IBS improved dramatically, too, since it decreases cytokine production in the intestines and increases calcium absorption which slows smooth muscle contraction.

 

Perhaps this explains why antihistamines have been helpful to some with PANDAS?

 

GREAT info at nutripedia > http://www.nutripedia.com/Amino_Acids/L-Histidine.html

 

There are some natural health practitioners who have used L-histamine for ADHD etc. Seems they may have been ahead of the "science?" :)

 

http://www.add-adhd-help-center.com/Ingred.../lhistidine.htm ( A helpful food list at the link as well).

 

Histidine Food Sources

 

Bananas and grapes, meat and poultry, and milk and milk products are high in Histidine. It is also found in root vegetables, wheat, rice and all green vegetables, though in lesser quantities.

 

Sorry gang, I'm excited about the potential this research merits and wanted to create an information dump (if you will) as I do more digging. Thanks for your patience with me. :D

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Wow, this discussion is way over my head this time of night, but I wanted to comment on what my son's doc suggested recently. He said that I should give him claritin and pepcid AC. One of them is an H1 blocker and one of them is an H2 blocker (can't remember which is which). He also suggested Quercetin. He said that even if my son is not showing signs of allergies (sneezing, runny nose, congestion, etc.), the allergens in the environment still may be stimulating the immune response, thereby increasing pandas symptoms. I never did get around to trying these two meds b/c as I have posted elsewhere my kids are doing much better with spironolactone.

 

Interestingly, my son went nuts with zyrtec, but he seems to tolerate claritin ok. Also, my son's IgE's tested very high. Just throwing those unrelated and possibly irrelevant facts out there since we are trying to put the pieces of the puzzle together.

 

It would be interesting for some of us to try the combination of H1/H2 blockers and report back...

 

Stephanie

 

One wonders how this may be related to PANDAS given histamine is involved in the immune response?

 

http://news.sciencemag.org/sciencenow/2010...o-tourette.html

 

People with Tourette syndrome are plagued by unwanted movements and verbal tics that run the gamut from extra eye blinks and grimaces to involuntary grunts or even cursing. Although the disorder tends to run in families, little is known about its genetic basis. Now researchers have found a mutated gene that appears to cause the disorder in one extremely unusual family with nine afflicted individuals. Although this mutation is not the cause of the vast majority of Tourette syndrome cases, it may push researchers to investigate a mechanism—and potential treatments—they otherwise would not have considered.

 

Since the French neurologist Georges Gilles de la Tourette first described his namesake condition 125 years ago, scientists have puzzled over the cause. Much recent attention has focused on a brain region called the basal ganglia that is involved in repetitive behaviors and on the neurotransmitter dopamine. In 2005, a team led by child psychiatrist and geneticist Matthew State of Yale University School of Medicine, reported one of the first genetic clues to the disorder, a mutation in a gene called SLITRK1 that seems to be responsible for a rare handful of cases. But the function of SLITRK1 and its contribution to Tourette syndrome are still largely a mystery.

 

In the new study, State and colleagues examined a family in which the father and all eight offspring (six sons and two daughters) have the syndrome. Extensive genetic detective work led them to a mutation in a gene called HDC, which encodes L-histidine decarboxylase, an enzyme involved in the production of histamine, a signaling molecule with a wide variety of roles throughout the body. The same mutation was present in all members of the family who had Tourette but was absent in thousands of DNA samples from control subjects, who included unrelated people with similar ethnic backgrounds as well as a group of 720 Tourette patients, the researchers report today in The New England Journal of Medicine. The mutated version of the HDC gene likely results in a truncated version of the enzyme, which would result in reduced histamine levels, State says.

 

More info at the link above.

 

I posted recently that vitamin C may be helping my dd. The following link may explain why.

 

Some info on histamine from digital natropath: http://www.digitalnaturopath.com/cond/C376401.html

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This is very interesting...i'm still VERy Tired, so if someone can put this in easy terms

 

if you have allergies to ALL pollens, cats, dust mites.....do you want to add histimines or block them...?

 

i'm not getting this.....or you may do the inverse depending on you IG g or e......

 

when we would get remissions, we did always get one onset during the spring....

 

MILK??? I love milk and so do my kids......but even if you need histadine, doesn't it create more flem.. or is it the histamine that creates the mucus....

 

are we talking 2 different things...histamine,histadine???

 

Again sorry...so tired....

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Great additions to the discussion guys. Grace your suggestion on balancing brain histamine is very interesting. I also feel that I've seen traits of high and low levels in my daughter.

 

Fixit, here is more info on histamine in general.

 

http://en.wikipedia.org/wiki/Histamine

 

H3 is the specific histamine receptor that impacts the brain and thus would be related directly to regulation of neurotransmitters.

 

http://en.wikipedia.org/wiki/Histamine_H3_receptor

 

Interesting aside, I've read that B vitamins are important when it comes to helping the body properly convert histamine, notably B6.

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Interesting aside, I've read that B vitamins are important when it comes to helping the body properly convert histamine, notably B6.

 

that may be why the B vitamins are so helpful for the majority people with TS, especially B6 for neuro stuff in general

 

I think with this, depending on that unique genetic and biochemical "make up" of the individual, things are going to be variable again, but it sure does open up very interesting avenues of research, and add some more pieces to the puzzle of how the functions of the genes, immune system and Neurological stuff are so closely connected.

Edited by Chemar
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my apologies again,,,,but i seriously need to rest i think...and i can't seem to follow anything through....

 

is this what's being said...

 

you have or want histaDine...but it needs to be converted to histaMine....

our you are lacking hista D or M....(which one?)

 

but what if you kid has obvious allergies...but no signs of vitamin defiency in the B family......

 

is it also being suggested to drink more milk???

 

I am certifiably delirious so please be kind

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At this point I'm simply discussing and researching vs. suggesting anything in particular Fixit. I'm not sure what specifically to make of this research other than it could potentially bolster notion of an autoimmune relationship to TS ala PANDAS.

 

Also, I have no idea if promoting dietary changes (by increasing foods that promote histamine) would be of any help, but I'm planning to experiment a bit given we don't have any food allergies. As Grace indicated, it could be a matter of balancing H3 in the brain vs more or less for everyone involved. To my understanding H3 acts like a pacemaker and regulates other neurotransmitters? But again, I'm as clueless as anyone at this point. :)

 

Sorry I can't be more specific.

 

Posting two more studies for the record:

 

http://molinterv.aspetjournals.org/content.../77.full#sec-14

 

The complete report on the original study can be viewed here: http://content.nejm.org/cgi/reprint/NEJMoa0907006v1.pdf

Edited by Laurensmom
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I absolutely agree that one should treat this as preliminary research info and be very very careful about trying to alter histamine levels without knowing for sure whether one's child already has high or low histamine levels and or tolerance!!

Remember this gene mutation was found in one family with TS, and the control subjects did NOT show it, even the 700+ ones who also had TS!!

 

for some kids who tic more with dairy, or have inflammation from it, clearly adding milk is a big no no

 

same with kids who already have hyper allergic issues...increasing their histamine could be an extreme trigger!!

Edited by Chemar
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I agree fully Chemar. It's a new area and monkeying around with the immune system in unproven ways should be approached with caution.

 

I did find this article interesting as I just posted about how I think vitamin C may be helping my dd -

 

http://selfdevelopmentedge.com/the-role-of...min-c-part-iii/

 

The contents of this dissertation have introduced a multidimensional model for the attenuation of histamine-related mental illness via vitamin C supplementation. Both histamine and vitamin C affect the human body on multiple levels. Histamine plays many different roles in the body, including neuromodulation, neurotransmission, allergic mediator, inflammatory mediator, and gastric acid secretion stimulator. When histamine levels are in the normal range, the above processes are usually in equilibrium and functioning optimally. It is when histamine levels become too low or high that trouble can arise. One of the roles of vitamin C in the body is to modulate histamine levels; if histamine levels are low, vitamin C administration will cause small amounts of histamine to be released. When histamine levels are abnormally high, vitamin C acts as an antihistamine, destroying excess histamine and thus bringing this chemical down to normal physiological levels.

 

 

If true, this is very interesting!

Edited by Laurensmom
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Well, antihistamine send my child into a wild rage, so it could be something relevant to her condition. She also has almost no IgE- which activates mast cells to release histamine. I'll be revisiting these studies when I have more time. Thanks!

 

You're welcome. We have bad reactions to antihistamine as well. Instead of Benadryl making me sleepy I become agitated and wide awake. :) My dd also gets hyped up. *shrug*

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I absolutely agree that one should treat this as preliminary research info and be very very careful about trying to alter histamine levels without knowing for sure whether one's child already has high or low histamine levels and or tolerance!!

Remember this gene mutation was found in one family with TS, and the control subjects did NOT show it, even the 700+ ones who also had TS!!

 

for some kids who tic more with dairy, or have inflammation from it, clearly adding milk is a big no no

 

same with kids who already have hyper allergic issues...increasing their histamine could be an extreme trigger!!

 

i agree, 1 in 700 dose not make for a great indicator...i just can't make sense of anything anymore and didn't know if i was missing something other than we don't know which directin to go, but that allergies seem to play a big roll for all of us

 

i think i'm going to take the weekend off ;)

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I think the importance in the study is not in the particular genetic link in this case, but in the potential mechanism and treatment options involved in the discovery.

 

Laurensmom, I had to back off from looking at this stuff this weekend - it's hard to make sense of a deficiency of brain histamine when your body is overwhelmed by it peripherally! :D So many of our kids seem to do better with natural "anti's". Wish there was a way of knowing how those natural products affect H3 receptors - for ex, quercetin is supposed to be able to cross the blood brain barrier. And we know it helps to stabilize mast cells & somehow functions as a neuroprotectant, but we don't actually know what it's doing in there.

 

And so much of what histamine does is tied in with the other neurotransmitters. Consider the article I've posted below - it says "histamine modulates the glutamate NMDA receptor..." So for example, if histamine affects the glutamate pathway, odds are pretty good that glutamate also affects the histamine pathway because these things typically are shut off or triggered by feedback mechanisms. So isn't it possible that something like an error of glutamate metabolism or some other metabolic pathway related to histamine production/metabolism could also lead to low brain histamine?

 

I don't mean to be discouraging - this news is still an important puzzle piece - I'm just thinking it may not be quite as helpful for us here & now as I first hoped.

 

Prog Neurobiol (2001) 63: 637-72.

The physiology of brain histamine.

 

RE Brown, DR Stevens, HL Haas

 

Histamine-releasing neurons are located exclusively in the TM of the hypothalamus, from where they project to practically all brain regions, with ventral areas (hypothalamus, basal forebrain, amygdala) receiving a particularly strong innervation. The intrinsic electrophysiological properties of TM neurons (slow spontaneous firing, broad action potentials, deep after hyperpolarisations, etc.) are extremely similar to other aminergic neurons.

 

Their firing rate varies across the sleep-wake cycle, being highest during waking and lowest during rapid-eye movement sleep. In contrast to other aminergic neurons somatodendritic autoreceptors (H3) do not activate an inwardly rectifying potassium channel but instead control firing by inhibiting voltage-dependent calcium channels.

 

Histamine release is enhanced under extreme conditions such as dehydration or hypoglycemia or by a variety of stressors.

 

Histamine activates four types of receptors.

H1 receptors are mainly postsynaptically located and are coupled positively to phospholipase C. High densities are found especially in the hypothalamus and other limbic regions. Activation of these receptors causes large depolarisations via blockade of a leak potassium conductance, activation of a non-specific cation channel or activation of a sodium-calcium exchanger.

 

H2 receptors are also mainly postsynaptically located and are coupled positively to adenylyl cyclase. High densities are found in hippocampus, amygdala and basal ganglia. Activation of these receptors also leads to mainly excitatory effects through blockade of calcium-dependent potassium channels and modulation of the hyperpolarisation-activated cation channel.

 

H3 receptors are exclusively presynaptically located and are negatively coupled to adenylyl cyclase. High densities are found in the basal ganglia. These receptors mediated presynaptic inhibition of histamine release and the release of other neurotransmitters, most likely via inhibition of presynaptic calcium channels.

 

Finally, histamine modulates the glutamate NMDA receptor via an action at the polyamine binding site. The central histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system; the stress-related release of hormones from the pituitary and of central aminergic neurotransmitters; antinociception; water retention and suppression of eating. A role for the neuronal histamine system as a danger response system is proposed.

 

http://www.ionchannels.org/showabstract.php?pmid=11164999

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And so much of what histamine does is tied in with the other neurotransmitters. Consider the article I've posted below - it says "histamine modulates the glutamate NMDA receptor..." So for example, if histamine affects the glutamate pathway, odds are pretty good that glutamate also affects the histamine pathway because these things typically are shut off or triggered by feedback mechanisms. So isn't it possible that something like an error of glutamate metabolism or some other metabolic pathway related to histamine production/metabolism could also lead to low brain histamine?

 

I agree. I have been interested in excito-toxins and the glutamate connection for some time. I believe that MSG does play a role in increasing symptoms for my dd. We also avoid aspartame etc.

 

The reason that this research is encouraging to me personally, is that it potentially involves an immune response. I've read various things about how decreasing histamine in the body can raise histamine in the brain and perhaps visa versa? I'm not sure if that's true, but if it is, it could explain why some are helped with antihistamines? Another friend speculated that it may be about histamine balance? Regardless, I look forward to learning more.

 

Thanks for all your research and input Grace. :huh:

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