Is depression a problem for you?

Yes! Testing has proven low serotonin levels. I took Paxil for years but do not like the side effects. My genetic testing results have been interesting to analyze. I have added Beta B-12 to my supplements which contains methylated folate also. I also have CBS mutations which I’ve heard should be address before MTHFR. So I have an appointment in a few weeks with a new naturopath. I’m hoping she can help improve my serotonin levels. I’m also taking 5-HTP 100mg twice a day.

Yes, I get very depressed and can’t work out if it the MTHR gene or my circumstances. I take Coq10 and other supplements. Will try adding more regular B12 which I take sublingualy and hope it improves.

It can be a problem, I’ve had issues with it since I was young, but I also have Inattentive ADD which caused me much misery.

Also, antidepressants do nothing for me but give me a bunch of side effects. However, since I was diagnosed and put on medication a year ago I noticed that my ADHD medication regulates my mood.

I suffered from ADHD for most of my life, but developed good coping skills without realizing it—cleaned up substance abuse (alcohol and nicotine) in my 30s—and didn’t get a psych study of myself until age 49, after self-diagnosing ADHD. Yes, it did carry depressive periods when I would get overwhelmed, more and more frequently as I aged.

I had had my fill of chaos and feeling down at 49, did the tests and got medicated to end mood swings (Wellbutrin) and modify ADHD issues (concerta). Took for 15 years until fed and big Pharma games with contrived shortages convinced me to get off all pharma. My acupuncturist suggested I take an ample dose of Omega 3s and high DHA daily, along with Vits. C and E, prior to weaning. It was tough going back to no pharmacy at first, but I knew what was causing depression and overwhelm by that time, plus I felt untold relief NOT to be exposing my brain every day to drugs and what I feared would be their awful cumulative side effects.

Within a year (2012) I fell under the care of a remarkable functional med doctor who listened to all of my “symptoms” (lifelong) and suspected methylation issues, so put me on a pure (nutraceutical, not a drugstore formulary) of B-Complex; methylated (activated) forms of: B6 (50 mg/d), 1000 mcg B12, and MTHFR folate, 1000 mcg/d. Plus a multivitamin, Vit.s C, D, E (to address deficiencies) and titrated me slowly up to a daily magnesium glycinate dose of 600-800 mg; as well as 5-HTP, twice a day. This instantly helped me as much as the two Rxes had, without side effects.

This was not done in a vacuum, but with eating better and better lifestyle choices: I worked with her to revamp my cortisol “clock” that had always whacky (night owl, wired); I started getting a consistent 8 hrs of sleep a night, and stopped all but 1 c./d of coffee (MTHFR that I have stockpiles homocysteine, which is made worse by caffeine). A micronutrient panel she did on me showed an innate deficiency of phosphatydalserine (serine) that has effects on the serotonin process, so I take two pills per day of it. A year into this, I did a 23andme scan, and sure enough, I am MTHFR deficient: homozygous for C677T—that plays havoc with my neurotransmitter production and efficiency, esp serotonin; and can slow my various metabolism processes by up to 70% over “normal” scans.

To assist mood (already improved at the first tweaking with Bs) and detox, it was suggested I add SAMe (400 mg twice a day). Thirty-minutes of guided imagery tapes every morning before daybreak have allowed me to back off a 5-HTP in a.m., unless needed. All of this has helped immensely with depression (and ADHD). MTHFR definitely figures into mental processes—I am sure this has run back through my family of highly creative relatives, a majority of whom suffered from depression, ADHD and biploar and substance abuse, and I am sure if they had had our resources available to them, they, too, could have led happier lives.

MTHFR issues are not an easy puzzle to fix, and self-dosing is not a great idea—lots of complexities that trained (naturopathically oriented) nutritionists are skilled at overseeing, at least for the launch of your program.

I have been impressed at the work of nutritionist Trudy Scott <> who was featured last week in James Maskell’s Interpreting Your Genetics webinar. She has some excellent views on genes and depression, and I also recommend the work of Drs. Kelly Brogan (A Mind of Your Own) and Sara Gottfried on depression. You can find them both online. Further, Dr. Charles Gant, who reviewed my 23andme info three years ago to make excellent nutritional suggestions (including the SAMe), addresses the associated neurotransmitters present in various forms of depression (all part of the MTHFR picture) in the final chapters of his book, End Your Addiction Now!, with more clarity for the layperson than I have found anywhere else.


I have had symptoms of clinical depression since I was a child. When I was a young adult (19), I was put on SSRIs for the first time. They were completely ineffective and actually seemed to make the depression worse.

After more than 10 years, I went in for a psych eval because I was so tired of being given antidepressants that weren’t helping. I had raging generalized anxiety, severe social anxiety, and terrible depression. The psychologist diagnosed me with bipolar II, even though my “manic depressive cycles” were usually less than a day in length (they are usually 3 months or more for true bipolar). The bipolar meds made my depression worse and caused terrible side effects including skin blistering and flu-like illness. I became violently ill and was completely bedridden for the better part of a year (in my mid-30s). No doctor from our local university or the Mayo Clinic could explain my illness. I even saw a top geneticist who shrugged and said he didn’t know what to test for.

I went home and ordered a 23andme kit. Lo and behold, I have MTHFR c677TT. I found a local endocrinologist who said yes, all my symptoms can be caused by this mutation because of the way hypomethylation affects DNA replication. I started the Yasko protocol and began feeling better within a month. Now, I take prescription methylfolate (15 mg per day) along with hydroxycobalamin and other supporting nutrients, and I feel almost normal. I made sure to email my doctors at Mayo with this information. Hopefully, they will run one more test [MTHFR blood test] on patients like me, and it will be the right one.

Somewhat recently, I started seeing a trauma therapist because I had been a victim of spousal abuse for a long time. It turns out that I was also a victim of chronic child abuse but had blocked it. (I know what you’re thinking, but yes, it can happen. I had all the memories in my head but it was like they had happened to someone else.) My “bipolar” was actually a series of emotional flashbacks. I come from a medical background and would have thought it was complete fiction until it the flashbacks started getting less severe with neurofeedback. This revelation matters because childhood trauma + MTHFR c677TT = Depression

Honestly, though, treating MTHFR hasn’t done much for my depression compared to other treatment protocols. I have a lot of serotonin-related mutations independent of MTHFR for which supplementation made a big difference. I do recall, for the very short time I took oral birth control (it made me extraordinarily ill–migraines, flu-like symptoms, brain fog, irritability), that it also worsened the depressive symptoms. I imagine, if I didn’t have these other issues (I can’t make or transport serotonin very well), I would notice a bigger difference from additional folate and B12.


I too have tried every antidepressants on earth. It turned out that thru both 23andme’s and Geno’s rare data and uploading it to Promethease for 5 dollars led me to the answer. I had my DNA done before the FDA would not allow us to know our own genotype mutations. I found out one that I could not convert T4 to T3 readily. So despite having borderline low T4 while on 200 mcg and border line low T3 and normal TSH I was hypothyroid. The day my psychiatrist put me on and additional T3 I was a new person. No longer walking dead. I was also no longer what we thought was depression I was simply hypothyroid. Then I switched to dessicated thyroid and now the world is vibrant and I love living. I too have severe ADHD. I take Adderall XR 20 mg XR twice a day. It also changed my life. I am able to access my intelligence which is Mensa qualified. I studying your snps after having 23andme Promethease analysis it I was found to not be able for it to pass the blood brain barrier. Wellbutrin worked a bit in addition to Adderall XR as did Nuvigil. Don’t give up. I am fine now after 25 years of trial and air. I just take Armour Thyroid, Aderrall XR and feel great.

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Thank you for sharing your information and experiences :slight_smile:
It’s good to have someone who can relate to my situation somewhat.

I’m glad that you were able to get some useful tests done. :smiley:
I wish I could afford to get more done for testing, someday.

I would like to get my b6 and zince levels checked at some point, but it’s like pulling teeth to get my doctor to run certain tests, I’m not sure why, insurance maybe?

I used to have mild hypothyroidism which went away after medication, then it turned into hyperthyroidism, so they took me off the medication and I’ve been fine since… pretty weird, but my physiology is weird…, my folic acid was fine at <11 and my b12 was at 600, but I eat a high protein diet, quite a few green vegetables and take supplements already. I thought it was interesting that with as much b12 and folic acid I was getting my levels weren’t higher, but I guess I’m using them and/or not getting as much as I think I am.

I can sympathize with having had dependencies as I have had my share as well, which fortunately I realized were just a crutch and not what I really needed … also, having more than 2 standard drinks gives me migraines… so, that’s helpful in cutting down as well.

   Coping skills only have taken me so far since, in addition to the ADHD-PI,  I also have learning challenges, anxiety, depression, brain fog and fatigue that I'm constantly fighting to control. 

 I am constantly in search of answers and supplements that will help. It seems I have a long list of genes related to methylation, at least according to livewello. I posted them below.

  It's pretty astounding.... I never had a chance... :smiley:  Currently I'm on 40 mg Vyanse which works well for pretty much everything - focus/ concentration, anxiety, depression ... but I know it's not good for me so I only take it 2 to 3 days a week for my college classes and if I really need to get extra work done... in addition to that I take a whole food multivitamin that has P-5-P, choline, methylated folic acid and methylated b12, I also take extra magnesium:calcium (500:1000 mg), extra vitamin C (perks me up and helps clear my head a little), about 25 mg extra zinc in addition to the 15 mg in my multivitamin (I noticed a mood and energy increase with this), D3 5000 iu (the D3 due to chronic deficiency), and fish oil which tends to make me sleepy so I take it at night.  

 During my Vyvanse off days I take N acetly l tyrosine and velvet bean, which works o.k, but not quite enough. I am going to add megafolinic acid ( methylfolate increases my brain fog and fatigue) and extra methylated b12 (I noticed some extra clarity, focus and increased mood when I tried this before, but it burns off quickly it seems so perhaps 2 times a day will be better). Green tea, raw cocoa and some coffee are also helpful. 

Also, I have cleaned up my diet, eating a high protein, healthy carb, low to no sugar diet… which also was very helpful.

Unfortunately, wellbutrin caused me to have worse anxiety, which turned into depression, 5-htp makes me very hyper and worsens my brain fog, SAM-e makes me more anxious and doesn’t do much more than that, and phosphatydalserine increased my focus and creativity a little bit, but makes me too sleepy and eventually it depressed me.

I also have issues with being a night owl, it seems I also have what is called the “night owl gene” or something which also related to ADHD if I recall correctly.

I’ve read some an article or 2 written by Trudy Scott, I find her articles interesting and possibly useful… that’s what lead me to try taking the extra zinc. It’s not really clearing my head or helping me focus, it’s already given me a temporary lift in mood and energy after I take it, but it doesn’t last … I’ve only been taking it for a little over a week and I know supplements take time to work.

My genes related to methylation, yikes!

ACE rs4343 G AG +/-
AGT rs699 A AG +/-
BHMT-02 rs567754 T CT +/-
BHMT-08 rs651852 T CT +/-
CBS rs2851391 T CT +/-
CBS A360A rs1801181 A AG +/-
CLCN6 rs3737964 T CT +/-
COMT rs6269 G GG +/+
DAO rs3741775 C AC +/-
FOLR2 rs651933 G GG +/+
FUT2 rs602662 A AG +/-
GAD1 rs10432420 A AG +/-
GAD1 rs12185692 A AC +/-
GAD1 rs2058725 C CT +/-
GAD1 rs2241165 C CT +/-
GAD1 rs3749034 A AG +/-
GAD1 rs3791850 A AG +/-
GAD1 rs3828275 T CT +/-
GAMT rs17851582 A AG +/-
GAMT rs55776826 T CT +/-
MAOA rs6323 G GT +/-
MAOB rs1799836 C CT +/-
MTHFD1 rs1076991 T CT +/-
MTHFD1L rs6922269 A AG +/-
MTHFD1L rs803422 A AG +/-
MTHFR C677T rs1801133 A AG +/-
MTHFS rs6495446 T CT +/-
MTR A2756G rs1805087 G AG +/-
MTRR rs1801394 G AG +/-
MTRR A664A rs1802059 A AA +/+
NOS2 rs2248814 A AG +/-
NOS2 rs2274894 T GT +/-
NOS2 rs2297518 A AG +/-
NOS3 rs1800779 G AG +/-
NOS3 rs1800783 A AT +/-
PEMT rs4244593 T GT +/-
PEMT rs4646406 A AT +/-
SOD2 rs2758331 A AC +/-
SOD2 rs4880 G AG +/-
SOD3 rs2855262 C CC +/+
TCN1 rs526934 G AG +/-
TCN2 rs1801198 G GG +/+

No, it is not a problem for me, but this book has a section about MTHFR that is helpful and includes depression as a possible side effect.

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Not sure if you’ll ever see my post here as it looks like it has been a few years since you posted this, but here goes… you and I have some similar mutations, I’m specifically looking at the MTHFS, MTRR ++, and I’m also ++ for BOTH TCN1 and TCN2. I haven’t been able to find many other people who also have the TCN mutations like myself. Apparently they are rare mutations somewhere around maybe 5% or less of the population?

Anyways, just wondering how you’ve been feeling and how your recent B12, MMA, and folic acid levels are?

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I can only respond with my recent diagnosis of MSA

Hello frenchmoxie,

fortunately I was notified in my email about your message. :slight_smile:
So anyways, it’s nice to meet someone else who has similar genetic mutations.
I didn’t realize the TCN mutations were so rare. That’s really interesting.

In response to your question about the b12, MMA, and Folic acid levels… I’ve only been able to get them checked one time and they were within in normal range.
I make sure to take a good multivitamin though, so maybe that’s been my saving grace.
When I can afford it I plan on ordering my own blood work though, because doctors just don’t seem to want to help in that manner for some reason.