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Dopamine concern

Messages
5
I am new to all of this but learning as much as I can. I have been fatigued and have had mood disorders for the last 10 years or so that has been progressively getting worse. It progressed into depression. My immediate concern is what is going on with my Dopamine. I researched depression and concluded that a lot of my issues appeared to deal with Dopamine. My doctor agreed and she put me on Welbutrin. It has helped a lot. I am no longer depressed and my mood has been entirely positive. I have been taking it 4 weeks now. I will be seeing a doctor in my area that has been mentioned on this forum a few times. I want to be educated when I see him. I am very confused with all of the mutations that contradict treatment of each other. Any insight or advice is appreciated. Here are my 23andme/Genetic Genie results.

Homozygous:
  • COMT V158M
  • COMT H62H
  • VDR Bsm
Heterozygous:
  • COMT P199P
  • MTRR A66G
  • MTRR A664A
  • BHMT-02
  • BHMT-08
  • CBS C699T
  • CBS A360A
I had blood work done that revealed Folic Acid is normal >24.0 with a range of >5.0 NG/ML.
Vitamin D, 25 OH is 17 range says optimal is 30-100 NG/ML. Doctor recommended 5000 iu's of D3 daily. However, I read 25 OH may show that I am not deficient and just converting D really well. I believe 1,25 now needs to be tested to confirm. Thanks.
 
Messages
5
Not that I am aware of. My grandparents on my paternal side were alcoholics. I don't seem to have any issues. I used to smoke in High School but easily gave it up.
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
Can you look up these SNPs for me?

MAOB
rs2283729
rs1799836
DDC (This is both AAAD and 5HTD in the pathways below, helping create serotonin and dopamine as well.)
rs3735273
rs1451375
rs921451
rs2329340
rs1451371
DBH
rs77905
rs1108580
rs2007153
TPH2
rs4570625
rs17110690
rs4565946
rs10506645
rs1487278
rs11179002
TYR
rs1393350
rs1847134
rs1799989

These are all in the dopamine pathway. Here is a chart I made:

Amine Pathway.jpg
 
Messages
5
MAOB
rs2283729 GG
rs1799836 AA
DDC
rs3735273 GG
rs1451375 AC
rs921451 CT
rs2329340 CT
rs1451371 TT
DBH
rs77905 CC
rs1108580 GG
rs2007153 AG
TPH2
rs4570625 GG
rs17110690 AG
rs4565946 CC
rs10506645 CT
rs1487278 CT
rs11179002 CT
TYR
rs1393350 GG
rs1847134 AA
rs1799989 CC
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
@ppodhajski, that's a great chart - I've been wondering about those pathways. And that you have the cofactors, too, is wonderful.

Not to nit pic, but the phenylaline - is that supposed to be phenylalanine? Maybe I'm remembering wrong.
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
@ppodhajski, that's a great chart - I've been wondering about those pathways. And that you have the cofactors, too, is wonderful.

Not to nit pic, but the phenylaline - is that supposed to be phenylalanine? Maybe I'm remembering wrong.

Ha, yes, thanks. That happens to a lot. I need a full time proof reader.

And I need to add some cofactors on there as well. GCH1 uses Zinc, for example.
 
Last edited:

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC


Have you ever tried taking P5P (a form of B6)?

Few more genes to look up!
GCH1
rs4411417
rs752688
rs8007267
PTS
rs3819331

Here is your pathway flow so far. I can theorize that a lack of B6 (P5P), or if you have a problem metabolizing it could cause dopamine issues.

Amine Pathway sn.jpg
 
Messages
5
Few more genes to look up!
GCH1
rs4411417 TT
rs752688 CC
rs8007267 CC
PTS
rs3819331 CC

I am at the beginning of this journey so I have not tried anything. My concern is that if I start treating the underlying causes it could cause some ill effects with the Welbutrin (i.e. psychotic episode or something). I very much appreciate you taking the time to walk me through this.
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
That PTS rs3819331 CC is interesting and it uses ZInc as a cofactor. Looks like it could lead to BH4 deficiency which will leave you low in all the neurotransmitters.

http://ghr.nlm.nih.gov/gene/PTS
http://www.uniprot.org/uniprot/Q03393
http://www.nature.com/jhg/journal/v57/n2/full/jhg2011146a.html

There is scant research on this SNP but it seems associated with Autism:
http://onlinelibrary.wiley.com/doi/10.1111/j.1601-183X.2009.00521.x/pdf

There is a brand of zinc called Optizinc you might want to try.

Here is your final map. If I had these SNPs I would start with the Zinc and B6, then add Magnesium.

Amine Pathway sn.jpg
 

Hip

Senior Member
Messages
17,796
I have been fatigued and have had mood disorders for the last 10 years or so that has been progressively getting worse. It progressed into depression.

Since you had no depression 10 years ago, its triggering cause cannot not really be an issue of your SNPs, which remain the same throughout life.

What makes you conclude that dopamine is behind your depression, rather than serotonin? Have you ever tried anything (drug or supplement) that boosts the serotonergic system? High-dose inositol for example?

I myself find that both serotonergic and dopaminergic interventions improve my depression.

I hope the benefits of Wellbutrin continue for you, by the way. I had spectacularly good results from Wellbutrin (see this post), for both my ME/CFS brain fog, and for my depression / anhedonia.

Sadly, after two weeks on Wellbutrin, this drug completely stopped working for me. If you look online, and search for the "Wellbutrin 2 week honeymoon", you will see that several people have reported that Wellbutrin worked very well for them initially, but then after a few weeks stopped working.
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
Since you had no depression 10 years ago, its triggering cause cannot not really be an issue of your SNPs, which remain the same throughout life.

What makes you conclude that dopamine is behind your depression, rather than serotonin? Have you ever tried anything (drug or supplement) that boosts the serotonergic system? High-dose inositol for example?

I myself find that both serotonergic and dopaminergic interventions improve my depression.

I hope the benefits of Wellbutrin continue for you, by the way. I had spectacularly good results from Wellbutrin (see this post), for both my ME/CFS brain fog, and for my depression / anhedonia.

Sadly, after two weeks on Wellbutrin, this drug completely stopped working for me. If you look online, and search for the "Wellbutrin 2 week honeymoon", you will see that several people have reported that Wellbutrin worked very well for them initially, but then after a few weeks stopped working.

Yes, the genes stay the same but the enzyme activity of the gene can change from quite a few factors.

Age
http://www.genomebiology.com/2013/14/7/R75

Cofactor and Coenzyme availability
http://www.ncbi.nlm.nih.gov/pubmed/16214324
http://www.ncbi.nlm.nih.gov/pubmed/10089110

As well as temperature
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1594916/

SNPs in genes will make us more sensitive to those external factors.

I was on prozac, lamictal, seroquel, klonapin, wellbutrin, celexa, depakote, zyprexa....on and on. I no longer need any of them now and I have been sympton for one year thanks to Nutritional Genomics.
 

Hip

Senior Member
Messages
17,796

That study is on bacteria, whose environment can vary considerably with temperature, but is inappropriate for humans, whose temperature is tightly regulated at 37ºC.



I was on prozac, lamictal, seroquel, klonapin, wellbutrin, celexa, depakote, zyprexa....on and on. I no longer need any of them now and I have been sympton for one year thanks to Nutritional Genomics.

You make it sound as if you tailored a specific nutritional regimen for yourself which addressed your particular SNPs; but if I remember rightly, the crux of your regimen was riboflavin-5′-phosphate (R5P), which is involved in many SNPs, and so is not really specific to your SNPs.

The fact that R5P helped you is great; but I am not sure that you can say this was because you figured it all out from nutritional genomics.
 

Violeta

Senior Member
Messages
2,843
That study is on bacteria, whose environment can vary considerably with temperature, but is inappropriate for humans, whose temperature is tightly regulated at 37ºC.
Then what are heat shock proteins for?

I can't remember the last time my temperature was 37'C.

And fever certainly can take one's temp way above 37C.
 

ppodhajski

Senior Member
Messages
243
Location
Chapel Hill, NC
That study is on bacteria, whose environment can vary considerably with temperature, but is inappropriate for humans, whose temperature is tightly regulated at 37ºC.

Enzymes work the same no mater what the organism. But if that is too much for you to get right now here is one that shows genes in a human cell line.

Common gene expression patterns responsive to mild temperature hyperthermia in normal human fibroblastic cells.
http://www.ncbi.nlm.nih.gov/pubmed/23311377

I am wondering why you only picked that one to critique? Do that man you agree the age and Cofactor and Coenzyme availability?

You make it sound as if you tailored a specific nutritional regimen for yourself which addressed your particular SNPs; but if I remember rightly, the crux of your regimen was riboflavin-5′-phosphate (R5P), which is involved in many SNPs, and so is not really specific to your SNPs.

The fact that R5P helped you is great; but I am not sure that you can say this was because you figured it all out from nutritional genomics.

Your confusion and doubt is a sign that you do not understand Nutritional Genomics. If you are having an issue understanding this method I can explain it to you. You can say you are not sure of this method but it will not aid in your comprehension.

You can ask @ahmo about his Nutrigenomic experience as well.

You can read more about Nutritional Genomics here:
http://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=397
http://nutrigenomics.ucdavis.edu/?page=information

And I also posted another video in the forum that you might watch.