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Teach me about Dopamine


JAG10
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Well, it certainly puts a more favorable light on ADHD meds. So often, I hear it slammed - "I'm not going to give my kid a stimulant!" - but if you frame it as "I'm going to give my kid something to help raise his dopamine into a normal range" - same drug but a completely different spin, eh?

 

And while I still lean toward DS being low dopamine (motor issues, attention issues), there is a history of family addiction and let's not overlook video game addiction (not that anyone here has ever had to deal with that) :D

 

Finally, to further complicate JAG's last question of recptor blockage vs. overproduction, while the cleft puddle is busy filling up with "excess" dopamine, neurotransmitters "oxidize: while in that cleft (i.e. they "rust" and degrade and become unusable/non-recyclable) over time. That's why when you take an anti-depressant for a long time, it "poops out" and stops working. Unless you put new dopamine into the system, you eventually run too low on dopamine and no matter how much you increase your anti-depressant dosage, it stops working. So you do the long (6 week) process of tapering off and the the long process (6 weeks ) of starting a new anti-depressant. The whole time, you're contributing to oxidative stress and cell damage while the raw material (dopamine) puddles instead of being re-uptaked (?) by my friend Al.

 

Great discussion. Now someone tell me what to do! :D

 

 

Lions and tigers and bears..Oh, MY!! This has been a fascinating discussion throughout. Somehow, I think I should have paid more attention in my Advanced Bio or Micro classes in college :D I, like you LLM, just want someone to tell me what to do!! For years, I have tried to "put the pieces" of my son's puzzle together trying to use some of these "theories" as Kim rightly suggests that they are. I would look to symptoms trying to see if they were low dopamine, high dopamine etc. and then see his response to certain medications and if adverse....try to work back from that. Have dappled with supplements to see if I could cause a more natural increase/decrase in neuro transmitters to improve the attention and focusing picture, diminish the tic picture etc. None of it really ever seemed to work. My grandfather had Parkinson's so I keep that in mind for family genetics yet my aunt and her entire family (4 grown children) suffer from severe Restless Leg Sx...seems like opposite sides of the coin.

 

For starters, we lack any kind of good testing or data to really form a baseline from where to start and go forward. Sent blood for MC testing and project was completed. Blood was never tested. Sitting in refrig somewhere in OK, I suppose. Or, thrown away by now? We treated presumptively for 90 days with high dose daily antibiotics and many of the severe PANDAS sxs abated. Dilated pupils, choreic type movements etc. With no "proof" of high Cam kinase, I was fearful of continuing high dose antibiotics. He has not had Strep in several years (now) and that was our main culprit (Strep every Spring and Fall for years) so, in a sense, we seem to "outgrowing" some of the flares, roller coaster ride etc since he is not getting Strep as he once did.

 

Interestingly, speaking of the stimulants. We tried 4 different when my son was 8...total failure. We had to quit every single one within 10 days of starting them. He "appears" like a low dopamine kid. One would think that stims would be helpful. Attention/focusing issues yet he's a mainly vocal ticcer (not so much motor) and a little OCD. More ADD than ADHD. Concerta caused him to stay up all night and literally chew all the skin from his hands and pick it off his feet. Focalin- thought we were onto something good then on Day 10 he spent the day (attending 2 different MD appts) underneath the MD exam tables picking the paper rolls for the exam tables into little pieces making piles of little scrapes. He became super focused and soooo OCD on everything. He was running away from me in stores, very argumentative, no ability to listen or follow directions etc. All that stopped with stopping medication. We then moved on on to Vyvance (stim/amphetamine base) which caused sever dystonic, tardive dykinesia reaction. Tried Dex and that caused severe OCD. He was on none of these medications for longer than 10 days. It was sad because the stimulants helped his attn and focusing and he was so bright academically (at first). Told me for the first time in his life he felt smart.Sad to hear from an 8 year old that had struggled for years in school. By day 10- he was a different child, one I didn't know and the whole house of cards fell down.

 

So, by these pictures of the side effects from medications...he had different stuff going on in different parts of the brain causing different reactions/side effects. I was just never really able to make heads or tails of any of it to come to any logical conclusions of the "magic bullet" to make it all better. Without a good doc to figure it all out and guide me to, perhaps, a different class of meds that might prove useful...I gave up!! Lamictal, Zoloft and few vitamin supplements are all we use and things are OK. Not perfect, still have issues but copacetic and functional compared to where we have been. Neuro typical... No. Better- yes.

 

I am now relying on puberty and the outgrowing some of these behaviors as my magic bullet for improvement. Working for me- uuuhhh, maybe. At 12.5...still have a little ways to go. I'm at the point of going down on meds. Not adding more. Almost need to get a clean slate, so to speak. See where we are sans any medications to see where we need to go.

 

This whole topic is fascinating. I just lack the concrete knowledge to know where to go with it and 'act' with any firm footing I know what I am doing. Especially, with my child. I can't know how he is feeling and know what some of these meds/supplements and treatments are doing for him. He's a kid of few words on expressing how he is feeling and what is going on with him. He lacks the verbal expression and ability to share his "inner self." Often, by the time he does share...the symptoms/feelings have been brewing for quite some time. Although, he can vocal tic enough to drive you crazy some days.

 

Trying to understand all this is like the endocrine system with all the negative feedback loops and hormone responses from multiple brain/body areas (thyroid, thymus, parathyroid, hypothalmus, kidneys, bone etc)...antagonists, agonists, low D, high D, what are the SSRI's doing to sites, clefts, puddles...OMG. Need a PhD in molecular biology to keep it all straight. :wacko: And good testing data...we don't have any of that so it is like trying to put a 1000 piece puzzle together and when you get to the end of the box- 300+ pieces are missing.

 

Anyway, just wanted to pass along... I have enjoyed the string of posts. Can't bring myself to really act on any of it but interesting to the science research junky that I am :lol:

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what I understand is that the question is not about lows and highs. when the process is as complex, the question is of balance. so, how do we establish balance exactly?

going slowly is one way.

addressing as many parts of the puzzle (kid's condition) as you can.

as time passes, you get more experienced at it and, hopefully, kids get better.

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Moderately high Dopamine levels make us on-guard, suspicious, and prone to misinterpret experiences in the environment. Known as an “idea of reference” in psychiatry, we begin thinking unrelated experiences are suddenly directly related to us. People observed talking across the street are now talking about us. As Dopamine increases, it can become so intense that we feel the radio, television, and newspaper contain secret messages directed at us from Hollywood or elsewhere. It’s as though we are attempting to incorporate/add everything we witness into our life. Planes flying overhead are snapping pictures of us and motorists talking on cellular phones are calling in a report on us. Our mind speed increases and races in an attempt to add all we see into our life. In an attempt to make sense, we may become extremely religious, paranoid, or feel we are a very important person. Increased Dopamine also increases the perception of our senses, as though turning up the volume in all our senses – hearing, vision, taste, smell, and touch.

 

I've personally experienced a bit of this. When I consistently take 1000mg of tyrosine for a few days, I start to get waves of a painic feeling of a religious nature...thinking about going to eternal damnation (the other word was censored). It was a real light switch moment for me to realize how much our neurotransmitters contribute to our responses.

 

I took the tyrosine because it pulls away the gauze curtain from my brain and doing daily tasks becomes easy...that's the best way I can explain it.

 

I also want to point out, that I've been told by my doctor that exercise has been shown to balance neurotransmitters too...although I just took his word for it, and didn't research it. I just wanted to put that out there since the question of balance came up...exercise can be a piece of the puzzle that some may not have considered.

 

Sending best wishes to everyone :)

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OK... you guys mention amantidine. I just looked up it's use, and it mentions antiviral, and also sometimes helps Parkinson's, ADHD and some others. Here's another thought. We know that Parkinson's affects the basal ganglia, and we also know that PANS is caused by dysfunction, inflammation, etc. in the basal ganglia. There is also some research that is showing a possible viral link to these disorders. What if, it's not only treating the dopamine levels, but also treating an underlying virus that is causing the symptoms of all of these disorders?

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.if you try and use meds to regulate the dysregulated areas, will you upset the apple cart in other areas? I guess all that's left is trial and error.

My personal guess is that a child can have some "baseline dopamine dysregulation" that is made more unstable and magnified beyond recognition with infections. Some kids may not have any baseline dysregulation- those would be the completely normal to nuts kids and some may have a considerable amount.

 

Yes - you can "upset the applecart" in different areas. For example, one theory of schizophrenia that is due to too much dopamine in the limbic system... so they give the individual meds to block dopamine, which does reduce hallucinations. The meds are better now, but the older dopamine blockers often produced some parkinson symptoms early on due to decreasing dopamine in the basal ganglia. Additionally the brain has plasticity and changes over time. The number of receptors actually change over time. So, people with schizophrenia who are on dopamine blockers for a long period of time actually can develop MORE dopamine receptors to try to accommodate for this. As they develop more dopamine receptors in the basal ganglia, they can start having unusual muscle movements called tardive dyskinesia. I believe this is seen less often now than in the past as I think newer drugs are better and controlling for this. However, that is why we need to be carful with meds that mess with these levels. It is not as simple as it looks on the surface.

 

 

And, back to my "viral" discussion...there is research also showing the possible connection between schizophrenia and viruses. So, is a virus changing the level of dopamine, and if so, if we treat the viruses, will the dopamine levels become more normalized?

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The main reason I asked Dr. O'Hara about Amantadine for my dd13 was because of the family history of Parkinson's, MS and ADD on my husband's side and low prolactin on my side (influenced by dopamine)From what I've read, Amantadine is no longer effective for influenza A, but who knows.

Karen- thank you for sharing. I wonder if you took a "low and slow" approach to tyrosine if you would be able to find your sweet spot? Amantadine comes in liquid and 100 mg capsules. I have a phone consult on Tues with her and my questions will be specific with the titrating process for Amantadine. I'm thinking the liquid gives one much more control to go low and slow similar to what we would hear for an SSRI.

Those who have tried Namenda, have you had similar experiences? Was it a standard dose or did you need to find a sweet spot not to upset your kid's apple cart?

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I'd like some clarity around histamine, which in addition to its role in allergies and ulcers is also apparently a potent brain chemical (neurotransmitter).

 

Specifically, I'd like to learn more about the histamine 3 receptor (histamine has 4 kinds of receptors). H3Rs live in brain cells where they're involved in sleep, appetite, and mood (sound familiar??)

 

Blocking H3 receptors enhance the release of neurotransmitters such as histamine, acetylcholine, dopamine, and norepinephrine, among others. This is going to prove an important receptor in the pathology of PANS, I predict.

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This is a very timely thread.

I have been pondering this of late.

 

Here are ds cunningham.

Remember first draw ds was on added taurine bid for 3 months..with other aminos to balance.

His tics were minimal/less but still there..and that is why I say if it is out range..and you have pandas symptoms you are still in episode

 

Ds was 9 ¾.

Dr C..whom I still respect..even though I don’t think there should be a limit on what the Cam reads, said not likely pandas

I told dr L I canceled my original appointment as I thought she would not believe it was pandas…due to the low Cam and ds is mostly just ticcer...yes dialated eyes, and dysgraphia(but not worth mentioning)…She said yes she would.and also noted his D1 was still quite elevated. D2 also noted as elevated by she and Dr. C.

 

He is all ticcer, all the time…so it doesn’t fit with some of the other things mentioned here regarding d1,d2, limbic sytems etc….

 

Cam 105…control 93

 

Anti-lysogangiosde

Paitent 160

Pos control >1280

Neg control 80

Normal range 80-320

Normal mean 147

 

Anti tubulin

Patient 500

Pos control 16000

Negative 250

Normal range 250-1000

Normal mean 609

 

Anti dopamine 1

Patient 2000

Pos control 8000

Neg control 1000

Normal range 500-2000

Normal mean 1056

 

Anti dopamine 2

Patient 8000

Pos control 16000

Neg control 2000

Normal range 2000-16000

Normal mean 6000

 

 

 

 

 

 

2nd draw ds was 10 in full flare…

Note…all the numbers are exactly the same…but the D1 is even higher.

 

Cam 160 normal 87

 

Anti-lysogangiosde

Paitent 160

Pos control >1280

Neg control 80

Normal range 80-320

Normal mean 147

 

Anti tubulin

Patient 500

Pos control 16000

Negative 250

Normal range 250-1000

Normal mean 609

 

Anti dopamine 1

Patient 4000

Pos control 8000

Neg control 1000

Normal range 500-2000

Normal mean 1056

 

Anti dopamine 2

Patient 8000

Pos control 16000

Neg control 2000

Normal range 2000-16000

Normal mean 6000

 

 

 

So one dr I had visited..who was an actual Dr. who did some sort of muscle testing. (not ART) who suggested that ds had LOW dopamine. I asked if he was sureand he said yes.

Mind you I already had 2 cunningham tests in front of me. That’s when I wondered about uptake.

 

The reason I am also posting this is that I am possibly considering a program that is suggesting that I give ds iv’s of Phosphatidylcholine, Glutathione (a powerful antioxidant) and Leukovorin. (folinic acid)and phenybutyrate(is this just a different form of butyrate?

.

The last item I see is used/experitmented with in parkinsons.

I am not sure I want ds to be the guinea pig here.

My question would be..is the dopamine we are measuring with cunningham..lack of reuptake..or excess.

Would parkinsons and TS respond the same to this treatment method.?

Is parkinsons lack of reuptake or lack of dopamine completely.

 

 

 

http://www.ncbi.nlm.nih.gov/pubmed/20201064

 

http://www.markpine.us/?p=3371

 

I think this one was posted before

http://www.ncbi.nlm.nih.gov/pubmed/22353286

http://carcin.oxfordjournals.org/content/26/6/1064.full

 

 

Does anyone have thoughts or experiences on any of the properties I listed?

Not trying to hijack thread….i was going to start a new one…but this seems like it ties in???

 

Ds was doing great…and all heck has broken loose.

I have had to put my attentions elsewhere do to some other emergencies here.

My writing is extra wonky because of stress and some fluid in my middle ear..making me feel like a weeble wable, also makes me feel slightly sleepy and REALLy Cant focus on what I type or speak…moving my eyes makes me feel like I am falling, but I need to keep taking care of the house of falling cards.

 

Thanks for any thoughts.

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Hang in there Fixit!

 

I have no answers; seems like a variation on questions we've been asking in this thread; high or low; production or reception.....and then......related to infection or not?

 

Were you saying the difference between test 1 and test 2 was supplements? Not illness?

 

Different types of dopamine, different areas of the brain and different symptomology.....so some kids with seemingly "opposite" symptoms can both respond positively to the same medication?

 

 

As far as being a guinea pig goes, it's the nature of this beast. Line up your possible interventions and do a risk/benefit analysis. That's why I am interested in Amantadine....it's very low risk, been around since late 1960's, operates as a different mechanism then meds she's already tried and those who have tried it for ADD mostly report positive results and the others report "did nothing", not much mention of "bad side effects." My dd13 is not a ticcer as a primary symptom, only when really sick with pandas and honestly, the ticcing was probably from stimulants. But my dh's aunt has Parkinson's, so we all swim in the same pool, if you know what I mean.

 

I really hope you feel better. Like all of this isn't overwhelming to begin with, when we are sick, it can become too much to bare.

 

Stay strong. jag

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  • 1 month later...

Sorry to jump in so late....I am new to the world of PANS but have been searching for answers to my daughter's problems for the past 3 years. Your discussion on dopamine caught my attention because of my constant attempts to keep it balanced. Some background....

approximately 4 years ago, my DD(then 11 yrs. old) changed completely from a giggly, eternally happy bundle of energy to a paranoid, angry, dark, depressed, shadow of her former self. She also began having a series of problems, including but not limited to psoriasis, eczema, mycoplasma pneumonia, ringworm, hookworm, severe acne, cysts (one removed), occasional swollen nodes, hives, rage episodes, cutting, anorexia, h. pyloria, hominis blasticystis, plantaris lichens,OCD, tics....well, you get the picture.

And this week, I have gotten tests back that confirm she has/had Bartonella, some type of mycoplasm, HHV6, and some bands of Lyme that show positive even though the overall test is negative.

For 4 years, I have not been able to get many answers and have been desperate to find some answers. My best help came after a local PA suggested the Yasko protocol.

Through Dr. Y, I had DD genetic panel done and learned that she has a polymorph on the COMT gene, and a single mutation on the MTHFR gene and the BHMT8+ gene. This has helped us tremendously. The COMT gene relates to the dopamine. COMT++ means that she has a sluggish enzyme to handle her dopamine. When the dopamine puddles due to the sluggish enzyme, it inhibits itself. This is what causes mood swings. It seems it is always either too high or too low and our goal is to keep the level balanced. It's quite tricky. The BHMT8 gene seems to consistently relate to viral/bacterial load.

She also showed in testing that her glutathion levels were non-existent.

I suspect that the genetics is why all these kids present differently with their various symptoms and behaviors. The level of dopamine overall would also affect how much dopamine is involved in different areas of the brain. And other genes play a role in how the brain handles the dopamine, as well.

The supplements on the protocol have helped tremendously but we are still trying to battle one infection at a time. Dopamine will not be balanced until we eradicate more of them. Dopamine levels are affected by viral/bacterial load and metals, along with diet, stress, hormones, and a wide range of other factors. Our hope is that we can cleanse the body of virus, bacteria, and metal (virus holds onto metals), so that we can then balance further with diet, supplements, etc. We also have to focus on her gut and the glutathion issues. Proper methylation is critical in keeping the load down once we eradicate the existing offenders. As long as I have breath, I have hope.

Anyway, I highly recommend the genetic testing to help you fully understand dopamine as each individual has a unique presentation based on their genetics, particularly the COMT gene and the VDR genes. I am certainly no expert and speak only of our journey. I am, however, a HUGE advocate of having a roadmap to help get my child to good health. I think that the future of medicine is all about epigenetics, being able to bypass or turn a gene on or off.

I am loving this forum and have learned a lot from all of you brave warriors.

QueenMother

 

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QueenMother - will you marry me? :wub: :wub:

(for background, I have been on a methylation/23andMe soap box for about a year and my friends are laughing as they read your post - I have a sou lmate in you!) FWIW - I didn't have my kids results when JAG started this thread. I've since found that both of my kids are COMT +/-. In addition, they also have MTRR, BHMT, VDR, MTHFR, NOS and CBS issues (each kid has a different set of issues). One child had/has lyme and Pandas. One is unclear. Seeing great progress by using methylation as a guide to treatments.

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You two can marry if you like but PLEASE don't have kids. :D No sense mixing those genes. :P I'm right behind you with the genetic testing. My daughter's results should be back in about a month. I too believe it is the missing link. I think we absolutely must get rid of the bacterial load AND treat methylation but as you said, it's going to be different for each child depending on their particular SNP's. Can't wait to see dd's results.

 

Dedee

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Oh, LLM! (batting my eyes here and smiling sweetly. can't believe there isn't a coy, flirty emoticon) Soulmates, indeed!!!! :wub:

Yes, I am very into the methylation process. It is very difficult to stay on the program and treat with antibiotics and herbal supps on top of it. We struggle with that but, happily, we are seeing major improvements. We have had almost 1 1/2 years of GREAT and then the flu hit here hard. The princess tanked. We are slowly coming back up now and my goal is to get her to a point that her immune system can handle things without her tanking every time. She is an amazing young lady until she flares....and this is the first bad flare she's had in a long time. After the flu, she stopped eating. Of course, that affected everything across the board. Then the cutting started which horrified me. It's been a rough few months but we seem to be getting back on track. Antibiotics helped break the cycle and Cumanda has been helping us a lot. We started it while waiting for the last batch of tests and I have been very impressed with it. Going low and slow with it but, as we parents can tell, I am seeing subtle differences that are all positive. Some days I actually see glimpses of my formerly giggly, happy child and I savor them.

Oh, and DeDee.....LLM and I would probably drown in our own gene pools!

Keep me posted on your progress with the methylation and genetics.

QueenMother

 

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Oh how I'd love someone to explain this to me too. I have often heard people say that their Cunningham D1 and D2 numbers were high and therefore the problem was too much dopamine. Yet is it that there's too much dopamine or that the receptors are blocked, therefore the dopamine backs up (like a clogged sink)and not enough dopamine gets through the pathways... that theory makes more sense to me. Because like your DD, my DS shows symptoms of not enough dopamine. Our kids share the attention issue/ brain fog stuff. Tics are often from too little dopamine. Parkinson's is too little dopamine. Anxiety and depression is from too little dopamine. Lack of motivation and behaviors that are reward-seeking like addiction are from too little dopamine. At least, that's the impression I have. But it gets quite confusing and for all I know, I have it all wrong.

 

But I do know that my son does better focus-wise with a tryosine supplement and tyrosine is a precursor to dopamine. So for him, adding dopamine has been helpful. But it may also be a problem of the receptors being blocked. So I'm not at all certain.

 

I know one of the genes that plays a role in dopamine synthesis is MAO. Anti-depressents are MAOI inhibitors. Like SSRIs, they cause more of the target neurotransmitter to pool up in between the neuron gaps, giving an additional shot of the good stuff to the uptake neuron. Jill - here's a geek paper on depression and tyrosine if you want to wade through it, but I'm not sure it will help answer your (very good) question. http://www.neuroassist.com/01%20Depression%20Johns%20Hopkins%20with%20cover.pdf

Don't quote me on this, because I don't know for sure, either, BUT...our Cunningham tests were extremely high D1, D2, but both my boys appear to have low dopamine.

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  • 5 weeks later...

Sorry to jump in so late....I am new to the world of PANS but have been searching for answers to my daughter's problems for the past 3 years. Your discussion on dopamine caught my attention because of my constant attempts to keep it balanced. Some background....

approximately 4 years ago, my DD(then 11 yrs. old) changed completely from a giggly, eternally happy bundle of energy to a paranoid, angry, dark, depressed, shadow of her former self. She also began having a series of problems, including but not limited to psoriasis, eczema, mycoplasma pneumonia, ringworm, hookworm, severe acne, cysts (one removed), occasional swollen nodes, hives, rage episodes, cutting, anorexia, h. pyloria, hominis blasticystis, plantaris lichens,OCD, tics....well, you get the picture.

And this week, I have gotten tests back that confirm she has/had Bartonella, some type of mycoplasm, HHV6, and some bands of Lyme that show positive even though the overall test is negative.

For 4 years, I have not been able to get many answers and have been desperate to find some answers. My best help came after a local PA suggested the Yasko protocol.

Through Dr. Y, I had DD genetic panel done and learned that she has a polymorph on the COMT gene, and a single mutation on the MTHFR gene and the BHMT8+ gene. This has helped us tremendously. The COMT gene relates to the dopamine. COMT++ means that she has a sluggish enzyme to handle her dopamine. When the dopamine puddles due to the sluggish enzyme, it inhibits itself. This is what causes mood swings. It seems it is always either too high or too low and our goal is to keep the level balanced. It's quite tricky. The BHMT8 gene seems to consistently relate to viral/bacterial load.

She also showed in testing that her glutathion levels were non-existent.

I suspect that the genetics is why all these kids present differently with their various symptoms and behaviors. The level of dopamine overall would also affect how much dopamine is involved in different areas of the brain. And other genes play a role in how the brain handles the dopamine, as well.

The supplements on the protocol have helped tremendously but we are still trying to battle one infection at a time. Dopamine will not be balanced until we eradicate more of them. Dopamine levels are affected by viral/bacterial load and metals, along with diet, stress, hormones, and a wide range of other factors. Our hope is that we can cleanse the body of virus, bacteria, and metal (virus holds onto metals), so that we can then balance further with diet, supplements, etc. We also have to focus on her gut and the glutathion issues. Proper methylation is critical in keeping the load down once we eradicate the existing offenders. As long as I have breath, I have hope.

Anyway, I highly recommend the genetic testing to help you fully understand dopamine as each individual has a unique presentation based on their genetics, particularly the COMT gene and the VDR genes. I am certainly no expert and speak only of our journey. I am, however, a HUGE advocate of having a roadmap to help get my child to good health. I think that the future of medicine is all about epigenetics, being able to bypass or turn a gene on or off.

I am loving this forum and have learned a lot from all of you brave warriors.

QueenMother

We recently got Yasko results back for my daughter and she also has COMT +/+ mutations for both the v158m and h62h. She also is +/+ for MTHFR c677t and has VDR mutations as well.

I have to admit that I have not implemented many new supplements based on these results because I'm completely overwhelmed by the whole thing. We've been doing biomed for 6 years and my daughter's list of supplements is a whole page long, so I'm no stranger to complicated protocols. How do you choose which from the list to use? There's no way we could ever afford the whole enchilada, much less have the time to swallow all of the stuff. How do you do it? I thought that we would be getting an individualized supplement list, but the suggested supplements for everyone is an entire page long, then there are the 4 pages that are based on the mutations. I know there are answers in those reports that will help us if I can only figure out what to do.

 

My daughter's PANS symptoms are fairly mild now compared to a couple of years ago, but we just can't seem to get rid of the tics and anxiety.

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