MTHFR gene impact on OCD/PANDAS

[gwr]

Hello,

I am a frequent peruser of this forum, though an infrequent poster (this may be my second).

We have been dealing with PANDAS/OCD for many years now - with the help of the physicians at MGH in both ID and psychiatry. After a particularly challenging episode last year my son (now 13) found some relief with a low (arguably, non-therapuetic) dose of Zoloft. Due to his swift and positive response (atypical for strep-induced OCD, I am told) we had a GeneSight test performed to get a possible sense of how he might react to other medications - surprisingly, nearly all of the SSRIs were in the Caution or Avoid category. The other useful bit of info was related to a mutation in the MTHFR gene (specifically "homozygous for the T allele of the C677T polymorphism). Both the subscriber as well as the advisors at GeneSight could not offer any clear information as to how to "treat" this i.e. folic acid vs methyl folate, etc. I am hesitant to make an appointment with a geneticist to discuss only this single, and common, gene mutation. So...I am wondering if anyone else on this forum has any experience with managing this mutation, with a combined use of folate/B vitamins and SSRIs, as it relates to OCD/anxiety...or, has any recommendation for a provider in the Boston-area (Cambridge/Arlington) who is well-versed in recommending supplements for teens.

Thanks in advance.

 

[LNN]

Since your DS is +/+, his body is struggling to convert any form of folic acid or folinic acid into methylfolate (+/+ means he's probably only converting about 10% of the raw stuff into the end product of methylfolate).

 

You need to introduce both methylfolate and some form of B12 (cobalamin) - since these work as co-factors and you need both as part of your supplement plan. You want to avoid synthetic folate (found in cereals and other fortified foods and most multivitamins).

 

I'd start with this product http://www.holisticheal.com/methyl-folate.html

because it's a liquid and each drop is 67mcg. So you can build up slowly and drop down quickly while you tweak dosing. Later, you can switch to a tablet if you find he does well on a 400mcg or 800mcg dose. If he needs more than that, you can get a prescription for Deplin, which comes in 5mg and 10mg doses. But for now, start with 1-2 drops/day (I put mine into a small dixie up of water). Do this for a few days.

 

Then add a sublingual B12 tablet. Any B12 that's swallowed doesn't make it into the blood stream - most of it doesn't seem to make it past the stomach acid. It's estimated that about 10% of a sublingual will get into your blood stream. So dissolving a tablet of 3000mcg of cobalamin will get roughly 300mcg into the blood stream. There are 4 forms of B12 - cyanocobalamin, which is the least desirable form and not very useful to the body. There's adenosylcobalamin and hydroxycobalamin -which is tolerated by most people. And there's methylcobalamin, which is good for people who are true undermethylators really need methyl groups. Which form is best for your son is going to be a matter of trial and error. If you happen to know the status of his COMT gene, this can help. But if you don't know it, I'd start with either 2000-3000 mcg of adeno or hydroxycobalamin. I'd start with one of these

https://www.seekinghealth.com/adeno-b12-60-lozenges

or https://www.seekinghealth.com/hydroxo-b12-60-lozengesor

https://www.seekinghealth.com/hydrox-adeno-b12-60-lozenges

 

Later, you can try methylcobalamin or different doses of any of the above to see if you can improve results. But these suggestions can get you started.

 

Start with a low dose of methylfolate (maybe 150-200mcg) and a few days later, add in a sublingual form of B12. Do this for a week. If you see nothing, or if you see improvement to mood, increase the dose of methylfolate to maybe 300-400mcg for a week, and assuming you still see improvements, keep increasing dose until you start to see "bad" mood stuff creep back in. Then, if you start to see mood swings or mania, stop both the methylfolate and B12 for a few days to let things "drain". Then re-start at the last dose where things were good.

 

While you're tweaking dosing, if you "overdose" on the methylfolate, you can give 100mg of niacinamide (vitamin B3) and this will quickly (20-30 min) soak up the extra methyl groups. Niacinamide is also useful any time you get rages. https://www.amazon.com/Source-Naturals-Niacinamide-Vitamin-Tablets/dp/B00020I7IU/ref=sr_1_2_a_it?ie=UTF8&qid=1489360057&sr=8-2&keywords=source+naturals+niacinamide

 

Hope this helps

[bobh]

Our PANS son has -/- for C677T so I have no experience on your question about folic acid/methyl folate. But I would like to ask: what was the sub-therapeutic dose of Zoloft your son saw improvement on?

 

We started 2.5mg of Zoloft (in a liquid form) after about 6 days of a 6-hour (or more) bedtime ritual (and many many days of 3-4 hours before that). On the evening of the 3rd day, he took less than 30 minutes to get to bed, and reduced further and stayed low from that point on, even when we got off that small dose. He did pick up some increased anxiety (apparently) with the Zoloft, however.

 

When we had other (different) OCD symptoms maybe a year later and tried Zoloft again, it didn't seem to do anything, even after increasing to 5mg (which is still very low).

[SuzanneR]

You shouldn't treat the MTHFR mutation without knowledge of other genetic mutations that also affect the pathway. You need to get a complete genetic test done (23andMe), submit the raw data to gene interpretation site (I've used LiveWello but there are other that people have recommended), then work with a doctor who's experienced in interpreting and treating the mutations.

[Bill]

We just found the same for our son - homozygous C677T mutation....

 

No expert here so take everything I say with a salt shaker of salt. My degree in genetics is from the University of Google this past week. We've been trying to heal my son for the past 12 years so I would NOT follow anything I say too closely unless to do the opposite perhaps. BTW - undiagnosed for 5 years, then PANDAS, then Lyme, now still fighting bartonella and babesia. Raging, dilated pupils, dystonia (like) symptoms, severe OCD, tics, depression, complete loss of math skills, things I've forgotten....Most symptoms are gone except the movement disorders. The depression and math skill loss just recently came back which caused us to do this testing......

 

Some observations. Our son has been very responsive to SSRIs in the past. He responded positively to 12.5mg of Zoloft the very first time he took it - within 2 hours. No doctor believed us. With our newfound knowledge of this mutation, the RN who requested the test theorized he reacted so quickly and dramatically because he was so deficient of serotonin,

 

I've read a lot of conflicting information regarding this mutation. You'll get a lot of different advice here as well. I (we) are not of the go slow mantra. It helps that my son doesn't really "react" to stuff. So - the RN put him on 15mg of Deplin. I added 8,000mcg of methylcobalamine. He started both as soon as we got them.

 

Of everything I read, you do want to treat with the methyl versions of both (Methylfolate, methylcobalamine).

 

My son's testing also showed that only two antidepressants were good for him. He was put on Pristiq this time based on the test.

 

So - he started the 15mg of Deplin last Saturday. He started the 8,000mcg of methylcobalamine last Thursday. He started the Pristiq on Saturday. There was no reason for when he started beyond that was when we got the different supplements and prescription.

 

As of last night, he was no better, no worse. But he also had IVIG ending last Tuesday so talk about slamming him with stuff - and then we took him back to college yesterday.

 

And if I understand how this works, the homozygous mutation means that my wife and I both carry at least one copy of the mutation. (someone correct me if I'm wrong) So - what's good for the gosling - well, you know. So I started taking 15mg of L-5-Methylfolate (calcium salt) and the 8,000mcg of methylcobalamin Thursday/Friday. No ill effect. I can feel a "buzz" or at least think I can. The methyl folate that I am taking appears to be the same as Deplin but is OTC and costs a lot less (MethylPro). I started taking these as I exhibit several of the possible symptoms. My daughter also exhibits some of the symptoms so just sent her some of each but at much lower doses (1,000mcg

for each).

 

And Saturday - I ordered the 23andme Ancestry and Health&Wellness test. We should get those soon. One we get those results (~2 months), and I do more degree training through the UoG, depending on my level of understanding and the results, yes - I'll probably have to find someone who actually understands it all.

 

 

 

[gwr]

Thanks all for the information, this is very useful and I appreciate the thoughtful responses. I have since been advised that we should check homocysteine levels and then go from there. And I am also going to order the 23andMe kit. As to the question about the Zoloft dose - we we were told 25 mg for 2 weeks and then 50mg after that (with the understanding that for OCD treatment the dose could go up to 200mg). After 3 days on 25 mg there was an improvement...far from normal but little improvements, such as the ability to sit at the dinner table, the hyperventilating all but stopped, etc...so after 2 weeks we never increased the dose...but did increase right before the start of school to 37.5mg, Again this is for a now 13yo. This reaction was unexpected - ASO and anti-DNase B titers were high, but we never saw improvement like this with long-term antibiotic therapy.

[bobh]

I understand 25mg to be a "normal" starting dose. But because you didn't have a significant worsening from that dose, all is well.

 

Just in case there are others following and interested in Zoloft dose, the really low dose for SSRI that may be necessary for PANDAS kids is described in this paper by Dr. Tanya Murphy and others:

 

https://www.researchgate.net/publication/228785018_Selective_serotonin_reuptake_inhibitor-induced_behavioral_activation_in_the_PANDAS_subtype

 

This basically says that some PANDAS kids (14 out of 38, or about 37%) get profoundly worse on that kind of SSRI starting dose (25mg for Zoloft, which is a trade name for sertraline).

 

It is because of this paper that we started at 2.5mg. Because we had such a dramatic improvement, I suspect our son is one of the sensitive ones.

[Rudy6897]

Hello,
          I just came across this wonderful site via a Google search of "PANDAS & OCD".
My first time here, so I'll introduce myself - I hope I can learn lots, but also contribute much of my experiences as I have fought the good battles with depression, anxiety, and OCD for 35 years of my 50 years here on earth!

My very first depressive episode was at age 15 following a night of beer drinking with other teenagers.  A year later, I came home from school with a severe strep throat, which is, magically, the very first time I began showing signs of OCD.
Little did I know until years later, that my OCD is probably a result of that PANDAS.

At 22, I discovered a name & options for treatment after seeing the Prozac pill on the cover of NEWSWEEK in 1990.
Best thing I ever did as a result of reading that article was convincing myself & my parents that I needed to see a psychiatrist.
Started Prozac in 1990 and I'm still taking it 27 years later!

But in my never-ending quest to be the best I can be, as I still fight the good battles everyday, I have been reading up on & exploring new horizons.  I've had my DNA tested with Genomind, showing I have the MTHFR mutations.  One of my doctors prescribed Deplin 15mg daily for me - I'm on about Day 10 and I'm not really seeing anything yet.  Placebo effect might have me thinking I'm gaining a little energy - we'll see.

The psychiatrist I've been working with after having my genetic testing  evaluated wants me to have several blood work tests done to check my Vitamin B12 & D levels, along with testing for lyme & inflammation.  He brought up the possibility of trying antibiotic therapy.  

I'm currently taking a multi-vitamin, Vitamin C, EPA/DHA, and various Probiotics as my "natural" augmenting agents.
I've tried all kinds of OTC snake oil to no avail.  
I want to believe that some of these supplements might be able to help, but I also think that my BBB (Blood-Brain-Barrier) is a solid iron fence around my brain, not letting anything get thru!

I just turned 50 and I am pledging to myself that I want to improve my quality of life by exploring all measures possible - I want to enjoy my "Golden Years" with my wife & family!

Glad to have found you'all!
 
                                 Sincerely,
                                                Rudy

  

[bobh]

To your pledge to "improve my quality of life by exploring all measures possible", and for the sake of those golden years:

I consider it wildly "lucky" that you have a psychiatrist that wants to try antibiotic (abx) therapy.  I say lucky only that it is one of those "measures possible".

On the one hand, we have Dr. Trifiletti in New Jersey, who has suggested abx to a ticcing parent of a PANDAS child he was treating, and finding it resolved the tics in that middle-aged person.

On the other hand, we have Dr. Miroslav Kovacevic who has said "ultimately, all abx eventually fail", as if to say, it works well when caught really early, but not so well after a long time untreated.

If it were me, I would first trial a good probiotic for at least a week (to know it doesn't make it worse), and then I would go for the abx.  You don't know for sure until you try.

[bobh]

Rudy6897: by the way, if you want to try an OTC supplement that has helped for us (our son), you could consider phosphatidylcholine in high doses.  I posted my statistically analyzed results here in this forum:

http://latitudes.org/forums/topic/18965-phosphatidylcholine/#comment-186762

There are also reports of improvement of PANS symptoms with CBD oil.