Teach me about Dopamine

[JAG10]

Hi friends,

 

This is piggy-backing off the Amantadine topic. Can you teach me about the dopamine receptor 1 and the dopamine receptor 2? The Cunningham test measures anti-neuronal antibodies in the serum that interfere with dopamine reaching those receptors? Which raises dopamine levels and causes behavioral symptoms????

 

What's the difference, symptom-wise, between the two receptors?

 

3boysmom commented that her son has HIGH dopamine levels.....is that determined by symptoms or in the serum? I think my dd13 has symptoms of low dopamine, specifically decreased attention/focus, decreased motivation, procrastination, boredom, decreased confidence, and some decrease with ease of verbal communication. These are typical ADD symptoms and make life a little harder than it has to be. These symptoms all completely resolve with prednisone, but what does that tell me? Does that mean the prednisone diminishes anti-neuronal dopamine receptor antibodies? You can't do Cunningham on steroids, so it must have some impact, right? Do steroids impact dopamine production? We both have low prolactin which has a direct relationship with dopamine as well.

 

Maybe she just has low dopamine that has nothing to do with PANS???

 

Amantadine is a dopamine agonist which means it should increase dopamine (reception?)

 

Am I totally confused or know just enough to be dangerous?????

 

Thoughts? help???

Jill

[LNN]

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

[3boysmom]

LLM I am just as confused, however the comment about the receptors being blocked is what our doctor wants to find out. Actually he sounds like he is trying to understand the difference between what Jag10 and you are saying. 2 years ago when we saw Dr. B and showed him our 3 boys' Cunningham test, he looked at low dopamine on one boy and said "I bet he has tics"....he did and the other boy D2 was 16000 and he said "he probably has OCD and not tics"....he did. So now the boy with OCD does have tics after the Coxsackie Virus and of course the Cunningham test is now 2 years old, so what does that mean??? He has major brain fog and zero attention and SLOW to do anything. I really want to try something for focus but don't have the heart to take a chance on the tic increase because he is already so loud and he sounds like a walking barn of animals...poor kid. Now you have me interested in tryosine supplement, is it a stimulant? Can it increase tics? Is your child or Jag10 child ticcers?

 

This doctor is not a PANDAS specialist "per-say" but I got his name from Professor Garth Nicolson when I reached out to him for Mycoplasma help. He is a quiet small town doctor that thinks 'out-side the box" and has been rejected by his fellow doctors. He has followed PANDAS since it's discovery and has a hobby in learning and reading and studying all about PANS issues. Professor Nicolson has been helping him treat and look for Mycoplasma for years and he looks for all types of infections. He is a very quiet modest man that reminds me of Mr. Rodgers (from TV). He wants to learn everything he can, so if he hears from Dr. Cunningham and gets that answer that is confusing us all....I will let you know.

 

PS. I will not share his name, as he does not want that. He is an old fashion doctor, but a genius. He does not have a computer in his office and the receptionists use old fashioned typewriters. He does his research from home on the weekends. AND get this: His wife is a psychiatrist and they both have very activly tried to get Texas Children's Hospital to look for infections before using SSRi's on kids, but he said no one will listen to him. He seemed to really enjoy the joint phone consult with Dr.T. because he got to talk to a doctor that thought like he did. Well anyway, I'll keep you posted.

 

CONFUSED,

Linda

Edited February 20, 2013 by 3boysmom

[LNN]

Now you have me interested in tryosine supplement, is it a stimulant? Can it increase tics? Is your child or Jag10 child ticcers?

 

My DS did not have elevated D1 or D2 on Cunningham. His CamK was 183. He was a huge ticcer at the height of Pandas days. He now only has mild tics when we get aggressive on lyme and he has trouble detoxing fast enough. (as in 3 weeks of tics 2 yrs ago on tindamax and 5 days of tics last fall when we added a 3rd abx to our combo - tics went away when we immediately removed the 3rd abx).

 

Tyrosine has not caused any tic issues for my son. I don't know if it's a stimulant - never researched it. Once I saw it was a precursor to dopamine, I didn't really care if it was considered stimulating. It helps his focus significantly. We've been using it for about a year. In December, I also added phosphatidyl serine twice daily. That is considered a stimulant. Phosphatidyl serine and Omega 3 are two of the main ingredients in Vyvanse - an ADHD drug. It too has helped, tho not to the degree the tryosine has. We're going into our second month of using it and it helped enough that I was willing to order my second bottle of 60 pills. But jury's still out whether it'll be a long term thing.

 

On tyrosine - try to wade thru the link I added to my first post. The doctor makes the point that you can't add tyrosine indefinitely without also adding at least a smaller dose of tryptophan or 5-HTP as a serotonin precursor. The two neurotransmitters need to stay in balance. Here is the followup link to the article, that discusses dosing for an adult: http://www.dr-bob.org/babble/20100122/msgs/935382.html

 

You can print these two out for your doctor and if he has any insights or feedback, please let me know. I'm not at all sure I'm understanding it all correctly. But as you know, when your kid is hurting, trying things and failing is sometimes better than just sitting by watching and doing nothing. Would love to live in a time when doctors could give me answers. But since they can't, I do my best to do no harm but to also try things that might help.

 

There is another resource on depression and tryosine/dopamine here: http://www.thewayup.com/ On the right side of the website is a yellow image of a book. You can download the pdf of the book from the site. it's a bit old - from 1994. So much knowledge has been refined in the past 20 years. I think epigenetics can give more individual guidance now. But the book is an easy read and gives you some helpful background.

[LNN]

Sorry Jill - don't mean to derail the thread. Would love for someone to offer a better understanding of dopamine.

[JAG10]

LLM I am just as confused, however the comment about the receptors being blocked is what our doctor wants to find out. Actually he sounds like he is trying to understand the difference between what Jag10 and you are saying. 2 years ago when we saw Dr. B and showed him our 3 boys' Cunningham test, he looked at low dopamine on one boy and said "I bet he has tics"....he did and the other boy D2 was 16000 and he said "he probably has OCD and not tics"....he did. So now the boy with OCD does have tics after the Coxsackie Virus and of course the Cunningham test is now 2 years old, so what does that mean??? He has major brain fog and zero attention and SLOW to do anything. I really want to try something for focus but don't have the heart to take a chance on the tic increase because he is already so loud and he sounds like a walking barn of animals...poor kid. Now you have me interested in tryosine supplement, is it a stimulant? Can it increase tics? Is your child or Jag10 child ticcers?

 

This doctor is not a PANDAS specialist "per-say" but I got his name from Professor Garth Nicolson when I reached out to him for Mycoplasma help. He is a quiet small town doctor that thinks 'out-side the box" and has been rejected by his fellow doctors. He has followed PANDAS since it's discovery and has a hobby in learning and reading and studying all about PANS issues. Professor Nicolson has been helping him treat and look for Mycoplasma for years and he looks for all types of infections. He is a very quiet modest man that reminds me of Mr. Rodgers (from TV). He wants to learn everything he can, so if he hears from Dr. Cunningham and gets that answer that is confusing us all....I will let you know.

 

PS. I will not share his name, as he does not want that. He is an old fashion doctor, but a genius. He does not have a computer in his office and the receptionists use old fashioned typewriters. He does his research from home on the weekends. AND get this: His wife is a psychiatrist and they both have very activly tried to get Texas Children's Hospital to look for infections before using SSRi's on kids, but he said no one will listen to him. He seemed to really enjoy the joint phone consult with Dr.T. because he got to talk to a doctor that thought like he did. Well anyway, I'll keep you posted.

 

CONFUSED,

Linda

 

Linda- which symptom set went with which receptor-d1 or d2? When dd13 was at her worst, she had it all but raging. The tics were the first to go and not seen in a long time. She is more OCD/anxiety and focus. If I look at both of our families there is plenty of addiction, Parkinson's, anxiety, ADD....across families it seems there is a low dopamine issue. I just wonder if this is separate from PANS? IDK, I have a phone appt with Dr. O'Hara next week and will ask but I'm afraid the answer will go over my head.

 

And when you say "receptor's blocked" you mean because there are anti-neuronal dopamine receptors antibodies in the blood binding to the receptors preventing the body's dopamine from reaching its destination effectively?

 

Has Dr. Cunningham explicitly concluded the relationship between the anti-neuronal antibody measurements and the Cam measurement?

[trggirl]

The dopamine levels are determined by neurotransmittor testing in the urine usually by a DAN doc or "outside of the box" doc. I think it can be done by blood but I have never heard of a regular doctor doing it. Regular doctors won't test it because the levels change quickly and so they feel the information is useless.

 

I have had my dd tested several times and I just look at it as information gathering. Just another piece of the puzzle. My thinking (which may be totally wrong, it's just my thoughts) is that if I catch a super, super out of range level, I think that is something that needs to be considered.

 

Interestingly, my daughter has always been borderline high on the dopamine yet Amantadine which supposedly acts at D4 helps her. There is so much that is still not understood.

[nicklemama]

Well to throw a wrench on things.....DS had elevated D1 and normal D2 on the Cunningham. He is primarily OCD. He doesn't tic unless things get really bad. His antitubulin was sky high. He was mildly ticcing when blood was drawn but still had a pretty good OCD going on. He had been on abx for 6 weeks and had a drastic improvement.. This was at dx.

 

DS just started a supplement with tyrosine and 5-HTP in it. It's in cream form and I have to come back later to talk about it. I have to run to book club. It's my night out once a month and I don't miss it, lol.

[JAG10]

Dopamine levels are determined by urine but Cunningham's level of anti neuronal dopamine receptor antibodies is done by serum.

Can Dr. Cunningham determine if a patient has high or low dopamine or only if they are producing high amounts of the dopamine blocking antibodies?

[3boysmom]

OK, I am home now and pulling out the huge binder of tests and notes and labs from the 3 boys over these 3 years!!!

Cunningham tests run 10-25-2010:

 

DS13 (then 10-almost 11)-Huge overnight dysfunctional OCD and body movements (NO TICS at the time)

Cam Kinase II score: 166

Anti-Lysoganglioside: 160 (normal range: 80-320)

Anti-Tubulin: 1000 (normal range: 250-1000)

Anti-Dopamine 1: 1000 (normal range: 500-2000)

Anti-Dopamine 2: 16000 (normal range: 2000-16000) VERY HIGH

 

DS11 (then 9)-night terrors, baby talk, personality change, HSP (No OCD & No tics)

Cam Kinase II score: 140

Anti-Lysoganglioside: 160 (normal range: 80-320)

Anti-Tubulin: 500 (normal range: 250-1000)

Anti-Dopamine 1: 2000 (normal range: 500-2000) HIGH

Anti-Dopamine 2: 8000 (normal range: 2000-16000)

 

DS10 (then 7)- Hyper, impulsive, immature, anxiety, and vocal & head tics (NO OCD):

Cam Kinase II score: 134

Anti-Lysoganglioside: 160 (normal range: 80-320)

Anti-Tubulin: 500 (normal range: 250-1000)

Anti-Dopamine 1: 1000 (normal range: 500-2000)

Anti-Dopamine 2: 2000 (normal range: 2000-16000) VERY LOW

 

 

The letter from the study says "We measure the levels of antibodies against the neural antigens lysoganglioside, tubulin and dopamine receptors D1 and D2." "Antibodies may induce increased signaling of neuronal cells and cause release of too much dopamine in the brain."

 

So the DS13 with high D2 (at the time) had no tics and the DS10 with low D2 had tics. Dr. B said that the results were what he would expect. So I wait in hopes that this very wonderful gem of a doctor will be ble to get Dr. Cunningham to clarify and then find that we may be able to try Amantadine after all and it will be the help that we need!

 

I hope this helps!

Linda

Edited February 21, 2013 by 3boysmom

[3boysmom]

Oh yea, I guess we can't forget to factor in the infections that each child of all of ours may have had at the time of the Cunningham tests. That would definitly effect the behaviors of what was going on with them.

DS13 had ASO 1720 and Anti Dnase 1920.

DS11 had ASO 626 and Ani Dnase 756.

DS10 has ASO 236 and Anti Dnase 450.

Edited February 21, 2013 by 3boysmom

[JAG10]

1361409906[/url]' post='154492']

"Antibodies may induce increased signaling of neuronal cells and cause release of too much dopamine in the brain."

 

 

Linda- Did this statement go specifically with one of the results? How could "too much dopamine" release be both the result of Very High d2 and low d2; both of whom are symptomatic albeit different symptoms?

 

1. And who mentioned d4.....where the heck does that fit in?

Edited February 21, 2013 by JAG10

[3boysmom]

Those statements were quoted from the cover letter that was sent generically with each participant in the testing and not specific to our results. Where did you get the D4 from?Didn't see D4 on anything.

 

Linda

[trggirl]

Oops, sorry to confuse things on the D4. I had read that one of the possible reasons Amantadine was effective for ADHD was because it is a D4 agonist. I thought it strange that my daughter responded to it since she has borderline high dopamine. This was not related to the Cunningham discussion at all. It was just more of an observation that neurotransmittor levels are still an unpredictable science. Sorry.

[kimballot]

 

The letter from the study says "We measure the levels of antibodies against the neural antigens lysoganglioside, tubulin and dopamine receptors D1 and D2." "Antibodies may induce increased signaling of neuronal cells and cause release of too much dopamine in the brain."

 

So the DS13 with high D2 (at the time) had no tics and the DS10 with low D2 had tics. Dr. B said that the results were what he would expect. So I wait in hopes that this very wonderful gem of a doctor will be ble to get Dr. Cunningham to clarify and then find that we may be able to try Amantadine after all and it will be the help that we need!

 

I hope this helps!

Linda

 

Ok- I have not had a chance to pull out DS's levels, but I will comment on this statement and couple of other statements made.

 

My understanding of the Cunningham test is that they take serum from our kid's blood - the part of the blood with the antibodies - and then put it in a little dish (or tube or something) with some type of neuronal tissue and see what happens.

 

When they put it in with donor basal ganglia neuoroblastoma cells (that would be live cells that originated from someone's basal ganglia), they can measure how much Cam Kinase is produced. Cam Kinase is an enzyme that is used in many neurochemical procsses, one of which is the production of dopamine. Kids with PANDAS make more cam kinase than other kids, but kids with syenham's chorea make even more... so the idea is that Cam Kinase must be leading to increased dopamine, which must be leading to our kids' problems.

 

Regarding the receptors - A neural synapse is the juncture between two neurons. Electrical impulses travel down the axon of one neuron and reach the juncture. The dendrite from the next neuron does not actually touch the axon from the first one. Instead... there is a cleft between the two In order for information to travel across it has to travel chemically. Different axons produce different neruotransmitters. When the electrical signal gets to the end of the axon, the neurotransmitter is released into the cleft. The neurotransmitter travels across the cleft and binds to receptors in the dendrite of the next neuron. The fit sort of lock and key in that certain neurotransmitters will bind with certain receptors. Once the receptor receives information, it will send a signal to turn the next neuon on. When enough signals are sent, the neuron will turn on and send an action potential down the axon to the next synapse... and so on and so on.

 

So... The problem with D1 and D2 receptors is that it seems that the antibodies in our kid's blood serum is locking into these receptors. So.. the the quote from the letter "Antibodies may induce increased signaling of neuronal cells and cause release of too much dopamine in the brain." indicates that we may have too much dopamine as a result of all of this.

 

I hope that makes sense and is not more confusing!