Why don’t antidepressants typically work with the MTHFR gene mutation?

In the previous post, I gave a couple of reasons why people being treated for depression have a problem passing on the “happy” neurotransmitters (Serotonin, Dopamine, Norepinephrine) from neuron to neuron in the brain:

  1. A lack of the necessary neurotransmitter being produced by the neuron
  2. Neurons that are hypersensitive to the neurotransmitter
  3. Neurons that are insensitive to the neurotransmitter
  4. The secreting neuron starts to reabsorb the neurotransmitter before it is passed on to the next neuron

The last of these reasons seems to be the one that is most targeted by antidepressants to alleviate depression symptoms. I like to think of the reabsorbing (reuptake) action of the neurotransmitter Serotonin in terms of a bucket, water and sponge.

For instance, in a healthy brain chemistry, Serotonin is naturally produced by ongoing chemical reactions in the body. The Serotonin is secreted from one neuron and passed on to a connecting neuron, building pathways throughout the brain. Don’t worry about the little hole in the bucket – the excess Serotonin is always reabsorbed properly by the secreting neuron to avoid an undesirable flood of Serotonin in the brain.

Typical

 

Sometimes with untreated depression, the Serotonin that is supposed to be passed on from one neuron to another is being reabsorbed too quickly by the secreting neuron. This is illustrated in the figure below through the enlarged hole in the bucket, as well as the enlarged sponge that is mopping up the Serotonin too rapidly. In this situation the receptor neuron does not receive an adequate amount of Serotonin before it is reabsorbed by the original secreting neuron.

Untrested Depression

 

Psychiatrists prescribe Selective Serotonin Reuptake Inhibitors (SSRI’s) to help limit the reabsorbing (reuptake) action of the secreting neuron, so that the necessary Serotonin may be passed on to the receptor neuron before it is reabsorbed too quickly. In the figure below, the SSRI is shown as a plug in the hole in the bucket. When the antidepressant is prescribed correctly, the correct amount of excess Serotonin is reabsorbed back into the secreting neuron.

SSRI

 

We now turn our attention to depression caused by the MTHFR gene mutation. As stated before, people with the more severe types of this mutation are very limited in their ability to convert folate into L-methyfolate, the active form of folate that is able to be absorbed and utilized by the brain and body. Once absorbed by the brain, L-methyfolate is then further converted into the enzymes which are involved in the creation of Serotonin.

Since people with the MTHFR gene mutation are unable to turn folate into the form that can be utilized by the brain to create Serotonin, they typically have very little Serotonin in their neurons. SSRI’s and other antidepressants (the plug in the hole in the bucket) typically have very little effect, since the neurons in the brain have very little Serotonin to start with. This is illustrated in the figure below:

MTHFR

In this example, the more reasonable solution for this type of depression would be to increase the amount of Serotonin going into the “bucket” in the first place. That’s where the supplement Deplin comes in. Deplin is L-methylfolate, which is allowed to cross into the brain to complete the chemical transformation into Serotonin, Dopamine, and Norepinephrine.

(Note: It was also suggested that I continue to take my antidepressant, since it works as the “plug in the bucket” to avoid excess reabsorption by the secreting neuron.)

In reality, there are several holes in the bucket and several sponges, with each one corresponding to its own particular neurotransmitter. Some neurotransmitters have been discovered and identified for its own job in the human brain. Some neurotransmitters have been discovered, but their jobs are not fully understood. Still others have not even been discovered yet. SSRI’s (Selective Serotonin Reuptake Inhibitors) focus specifically on the neurotransmitter Serotonin. Tricyclics and SNRI’s (Serotonin Norepinephrine Reuptake Inhibitor) are antidepressants that focus on both the Serotonin and Norepinephrine neurotransmitters. MAOI’s (Monoamine Oxidase Inhibitors) focus on all of the members of the Monoamine Oxidase neurotransmitter family, including Serotonin, Norepinephrine, and Dopamine. Trycyclic and MAOI antidepressants are older antidepressants that carry with them various side effects or dietary restrictions, while SSRI’s and SNRI’s are relatively newer classes of antidepressants that generally have fewer side effects and restrictions on diet.

I personally take Nardil, which is a type of MAOI. I’m not entirely psyched about the dietary restrictions associated with this medication, and I am also unable to take any other antidepressant medication or antihistamines while on Nardil. However, I’ve been feeling great for the past 45 days on both Nardil and Deplin, so I am really uninterested in rocking the boat at this point.

Thanks for reading, and please comment me if you feel that my information is inaccurate or misleading. Happy Easter!

What causes depression?

In my Holy Saturday post of my MTHFR blog, I will attempt to explain some of the causes behind the chemistry of depression in the brain as I understand it through my research. I am very interested in finding out more about the depression that has consumed my life for the past several years, and I would appreciate any comments from health care professionals telling me if my information appears to be misinformed or misleading.

Now… what is the deal with depression?

There can be many causes for depression in an individual, which include:

  • Biological DifferencesPhysical abnormalities within the brain
  • Brain ChemistryThe lack or excess of, or hypersensitivity or insensitivity to  neurotransmitters like Serotonin, Dopamine, and Norepinephrine
  • Hormones Changes in the body’s balance of hormones due to pregnancy, thyroid problems, menopause, or other conditions
  • Inherited Genetic TraitsSuch as the MTHFR gene mutation
  • Life EventsTraumatic events in the past or present

Treatment is often very difficult for depression because emotions are reliant upon the chemical reactions and neural connections within the brain. An article from Harvard Health Publications states that “there are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life”. Therefore, it is often difficult to even locate the problem within an individual with depression, much less treat it.

You may have seen this diagram of a typical connection between nerve cells in the brain, or neurons:

neurons

Basically, the diagram shows that neurotransmitters (chemicals that relay messages) are stored in one end of a neuron (called the axon), and are passed through the space between neurons (synapse) into the receptor site of another neuron. As stated before, there are millions or billions of these connections in the human brain , and the pathways that these connections make are in a constant state of change depending on what we experience and/or learn on a daily basis. Think of the pathways as an ever-changing system of railroad tracks, wherein the individual railroad ties represent the connections that make up each line of rail.

Although the reason for depression may stem from a variety of sources, the depression we “feel” is a result of either faulty connections between neurons, the rapid or gradual buildup of negative neuronal pathways in the brain, or both. For instance, a person who feels hopeless or worthless may build and reinforce these pathways over months, but a person who experiences a sudden traumatic event may experience a more sudden pathway change that may be reinforced over time without the help of some type of therapy.

I’m going to choose to focus on the faulty connections between the neurons at this point, simply because it is the major reason why psychiatrists prescribe medication. Negative pathways in the brain can theoretically be torn down and built back up again through talk therapy, self-help books, and various cognitive strategies. However, I believe that people with faulty connections between the neurons themselves more often require medication to boost the effectiveness of these individual connections.

(Please note that I am not inferring that one type of depression is more serious or valid than another, as I have experienced my share of talk therapy, self-help books, medication, and many other types of treatment. Many people with depression start with faulty connections between neurons, and the resulting feelings create negative pathways in the brain. I am simply offering that medication tends to affect the chemical process through which these connections between individual neurons are made.)

There are many different types of neurotransmitters, each responsible for relaying its own type of information. The many neurotransmitters in our brain are responsible for all of our brains’ functions, including learning, memory, emotion, perception, and the control of involuntary body mechanisms, just to name a few.

For the sake of brevity, this blog will continue to focus on some of the neurotransmitters that have been found to be involved with depression: Serotonin, Norepinephrine, and Dopamine. As stated before, each of these neurotransmitters are passed from neuron to neuron through a space called the synapse. Once the brain realizes that enough of the neurotransmitter has been secreted, it instructs the secreting neuron to stop pumping out the neurotransmitter and reabsorb the excess neurotransmitters left in the synapse back into the secreting neuron. People with depression treated by antidepressants often have a problem with passing these neurotransmitters on. The reasons for this problem may be:

  1. A lack of the necessary neurotransmitter being produced by the neuron
  2. Neurons that are oversensitive to the neurotransmitter
  3. Neurons that are insensitive to the neurotransmitter
  4. The secreting neuron starts to reabsorb the neurotransmitter before it is passed on to the next neuron.

My next blog will focus on reason #4, since most of the antidepressants out there seem to deal in varying degrees with the reabsorption (or reuptake) issue. The blog will also attempt to explain why antidepressants typically don’t work well for people with the MTHFR gene mutation.

 

38 Days and Counting! Info on the MTHFR mutation

I have been free from my depression symptoms for an amazing 38 consecutive days! I am starting this blog because I have some exciting news to share regarding my personal journey to treat my depression.

After taking a routine blood test in March, I found that I had a MTHFR gene mutation!

“Great!”, you say, “but what the heck is an MTHFR gene mutation?”

The MTHFR (Methylenetetrahydrofolate Reductase) gene is crucial to converting folate (a B vitamin that is naturally found in many foods) into a form that is able to cross into the brain and stimulate the production of the “happy” neurotransmitters (chemicals that relay information) in the brain – Serotonin, Dopamine, and Norepinephrine.

The name of this brain-active form of naturally occurring folate is L-Methylfolate.

Once absorbed by the brain, L-methyfolate is then further converted into the enzymes which are involved in the creation of Serotonin, Dopamine, and Norepinephrine. The chemical process described here might be more easily understood as a simplified diagram:

Image

People with one of the severe types of the MTHFR gene mutation are very limited in their ability to convert folate into L-methyfolate, which severely impacts their ability to create Serotonin, Dopamine, and Norepinephrine in the brain. The lack of these neurotransmitters has been shown to increase depressive symptoms, which is why this MTHFR gene mutation has been linked to depression.

I believe there are reasons why typical antidepressants don’t usually work with people with this type of gene mutation, but I’ll get into that in future blog posts.

As for treatment, I have taken Deplin since early March, and it has worked wonders for me! Deplin is a medical supplement (not a medicine) that contains high amounts of L-Methylfolate. Deplin comes in 7.5mg and 15mg tablets, and is the only one that I know of that is specifically geared toward depression due to the body’s inability to covert folate. There are many over-the-counter supplements containing L-Methylfolate, but they do not provide the amount needed by people with the MTHFR gene mutation (usually containing 1mg or less), and most of them contain regular folate that the bodies of people with this mutation can’t convert anyway!

(Please note that I am not a representative for Deplin in any way. I had never even heard of it before it was recommended to me after my blood test results came back. I am just a person who is thrilled with its results!)

At this point, it is important for me to recommend that you get a blood test to find out if you have one of the severe types of the MTHFR gene mutation before starting on Deplin! 

Unfortunately, psychiatry is sometimes a frustrating practice, especially when trying to treat someone who is seemingly unresponsive to antidepressants. Very often, attempted treatment turns into a “Let’s try this…” approach, where medications are prescribed by doctors much like they are attempting to throw darts at a target while blindfolded. Since Deplin is newer type of depression treatment, there are undoubtedly some uninformed doctors out there who will unwittingly throw Deplin at a patient under the “Let’s try this…” approach, without first finding out if they have an MTHFR gene mutation.

Patients without one of the severe types of this gene mutation tend to not respond to higher levels of L-Methylfolate, and typically could feel worse when bombarding the brain with unneeded amounts of this type of supplement.

The results of this test will show one of the following (in order of severity):

Most Severe

Homozygous 677 / Homozygous 1298  (Compound Homozygous, meaning you have two 677; two 1298)

Homozygous 677 / Heterozygous 1298 (Both parents passed down the 677 mutation; One passed down the 1298)

Homozygous 1298 / Heterozygous 677 (Both parents passed down the 1298; One parent passed down the 677 mutation)

 

Severe

Homozygous 677 / Normal 1298 (Both parents passed down the 677 mutation)
Homozygous 1298 / Normal 677 (Both parents passed down the 1298 mutation)

Heterozygous 677 / Heterozygous 1298  (Compound Heterozygous: One parent passed  down the 677; One passed down the 1298)

 

Less Severe

Heterozygous 677 / Normal 1298 (One parent passed down a single 677 mutation)

Heterozygous 1298 / Normal 677 (One parent passed down a single 1298 mutation)

 

Unaffected

Normal/Normal (For both 677 and 1298)

 

I happen to have the Homozygous 677 gene mutation with a Normal 1298. About 12-15% percent of the population has a Homozygous 677 or 1298 gene mutation. I have around 250 friends on Facebook, so that means this information could be helpful to about 30 people from my friends list!

My advice is to BE CAREFUL, and get yourself a blood test to discover if you have a severe form of the MTHFR gene mutation before attempting to take this supplement.

I hope to have more information on the MTHFR gene mutation in future posts.

My story

I am not a doctor, and I am certainly not someone that one would typically call a “blogger”.

I am someone that has struggled with treatment resistant depression for years, but has recently stumbled upon something that has considerably changed my life for the better. This has inspired me to want to share my experience with as many people as I can, in hopes that some may benefit from this relatively new (and often misunderstood) treatment for depression.

I have been dealing with depression for many years. I can remember having smaller, less debilitating bouts of depression going back to college about 17 years ago, but it seems that the crap really started to hit the fan about 6-7 years ago. At that time, I was a pretty successful and financially secure NY public school music teacher in a good district, and lived in a pretty nice home with my wonderful wife and two beautiful boys. Everything in my life was how it was supposed to be for me, and although I experienced the normal life stresses that people feel, I really had no overwhelming reason to feel down or depressed.

There was no definitive date or time that my depression started to overcome me – instead I gradually started to experience feelings of unworthiness and hopelessness. I went on a small dose of antidepressant to try and lift my mood, and it might have for a short while, but I eventually found myself slipping back down. I went back to the doctor to up my dose, but any positive effects would again seem to wear off after a couple weeks. So I changed medicines. I started to go to individual therapy to try and talk out my issues. Changed medicines again. However, all the while I felt my thoughts starting to spin out of control. The normal stresses of my job, family, and everyday life were getting to me more than ever, and the overwhelming dark feelings of sadness, loneliness, frustration, inadequacy, and hopelessness became a persistent central focal point of my life instead of fleeting moments of mental weakness. It felt like I was slowly crushing myself, and it was getting harder and harder to find the moments that I could “breathe”.

I had a neck surgery in December of 2011 to correct a slipped disc, and although I felt physically better after the surgery, my mental dam finally broke. I returned to school for one month after the surgery, and needed to go into the psychiatric hospital in March 2012 for suicidal ideations. After a week feeling like an inmate at a prison, I was finally released. I tried to get back to real life again and apply the coping strategies I had learned in the various groups I attended at the hospital. However, my mind started to slide away again, and I found myself back inside the psychiatric hospital in May 2012 after I spent a week at an outpatient therapy program. Things were getting more and more desperate for me, but I decided to go back to work in September after a summer filled with psychiatrist appointments, individual counseling sessions and group therapy. My year didn’t last long, as in October I found myself back in the hospital again. This time my psychiatrist had me try ECT (Electroconvulsive Therapy), which is basically what it sounds like. I spent the end of October into the beginning of November at various sessions where they would strap me to a table, inject me with general anesthesia, and shock my brain into seizure. The sessions were a far cry from the terrible illustrations of ECT given in One Flew Over the Cuckoo’s Nest, but still neither enjoyable or beneficial. My therapist and I decided that my job as a teacher was just too stressful for me at this point, and I ended up resigning from the job that I thought I was meant for in March of 2013. Without getting into too many specifics, my depression was winning its battle over me. I felt many things throughout the next couple months, but was mostly saddened and frustrated that I had lost something that I had put so much time and effort into, and not really knowing how or why.

Thankfully (and unbelievably), I still had my beautiful wife and great kids, but I was too stuck in my own head to give them the love and attention that they undoubtedly deserved. I began to retreat to my bed more often, and found myself sleeping for hours during the day to try and escape this personal hell that was eating me away. For the past 3 years, I was told that I needed to “pull myself out of it” or “talk it out”. I tried… God, I tried… but for some reason I couldn’t. I had been on countless types and amounts of antidepressant medication, in addition to the hospital stays, ECT, and talk therapy 3 times a week, but I just couldn’t avoid falling further and further. I found myself back in the hospital in January of 2014, and was prescribed Nardil (a Monoamine Oxidase Inhibitor, or MAOI that went out of style in the 1980’s due to its dietary restrictions) as a last resort, but I was finding no relief with that either. My therapists and doctors were great people who cared a lot for me, and were scrambling in frustration themselves trying to figure out how to fix me, but all they could tell me was that my depression was the result of… say it with me now… a Chemical Imbalance! I started to reject this abstract, nebulous, and overall (excuse my language) bullshit diagnosis, and began to do research on my own.

I found some things that I thought might work, and even got my psychiatrist to consider ordering them for me. One of these things was a developing ketamine clinic at the Dent building in Buffalo, which was a treatment that had shown promise in other areas in the country. Basically, ketamine is a 1970’s hallucinogenic party drug (“Special K”) that has been shown to alleviate depression symptoms in much smaller doses. He told me the name of the clinic’s head neurological psychiatrist, Dr. Capote, and I quickly went home to schedule an appointment with him. After waiting for a couple months, I was finally able to see him in February 2014. He ordered a humungous blood test for me, and one of the things it checked for was the MTHFR gene mutation. The blood work came back as positive for a homozygous MTHFR C666T mutation, which is one of the most severe types of this particular gene mutation. He recommended that I get on 15mg/day of a medical supplement called Deplin in addition to the Nardil that I had already been on since January.

I first started taking Deplin on Monday, March 3rd, and that Thursday was the first day I felt a real difference. As of today, it has been 36 days since that Thursday, and I have consistently felt better every day! This is significant because up until this point, the most I could hope for were 2-3 “decent” days strung together before I crashed again. I finally feel what I have perceived “normal” to be for many years. I am not “manic” or over-the-top happy, and there are still stressors in my life, but I am somehow able to deal with them in a way that I hadn’t before. For the first time in about 3 years, I feel as if I can “breathe” again. I interact with my kids and my wife in ways that I really haven’t in the past. I’m laughing again, and rediscovering the positives in my life rather than dwelling so heavily on the negative. I wanted to wait and see if this was just a “placebo effect” before letting the world in on my transformation, but after 30 days I have been slowly starting to put the word out to friends, family, and group therapy members. I have found through my research on this MTHFR gene mutation that although up to 60% of the population has some form of it, only 12-15% of the population have the more severe form of it which could possibly be helped by a supplement like Deplin. I have about 250 friends on Facebook, so that means there may be as many as 30 or more that could be helped by this treatment! Please read on to my future blogs to find out more information about this treatment that has changed my life!