Moody? It could be your Methylation.

Neurotransmitter levels can affect your mood, but did you know that other chemical processes in your body can have a also profound affect on how you feel? 

Quick Bite (for those of you with little time for details)

• Methylation is a chemical process in the body that indirectly effect’s the balance of neurotransmitters (the chemicals that transmit signals) in you brain. 
  
• Neurotransmitters effect how you feel. 
• In most people methylation works well but In a small proportion of people it can be over or under active. 
• Undermethylators have a deficiency of active neurotransmitters affecting their mood.
• Overmethylator symptoms are due to an excess of neurotransmitters causing over-stimulation. 

Long Lunch (read on if you would like to know more)

Behind the scenes in our brain 

Our thoughts, feelings and reactions are all the result of a mass of brain cells (neurons) communicating information. Brain cells don’t touch, they transmit information chemically and electrically. 

Signalling Cells

For information to be transmitted between two cells a little squirt of neurotransmitter (chemical messenger) leaves the end of one cell, and, all things going well, floats over the gap and locks into receptors on the neighbouring cell to create the signal. 

Once the signal (actually an electrical impulse) is sent, the neurotransmitter material is taken back into it’s original cell. There are several different types of neurotransmitters that perform  different functions and create many different moods. 

The three main neurotransmitters that effect mood are also effected by methylation.

• Serotonin - responsible for our sense of wellbeing
• Dopamine - helps us experience reward and motivation 
• Noradrenaline - famous for fight or flight we also need this to be alert

Mind the gap 

Simply put, in order for signal transmission to run smoothly we need:

• Enough of a particular neurotransmitter coming from the sending cell. 
• Enough of that neurotransmitter left in the gap between the neurons for the right amount of time. 
• Enough receptors on the receiving cell to collect the neurotransmitter. 

When it comes to methylation what happens in the gap is important.

Neurotransmitter transporters 

Neurotransmitters left in the gap need to be cleaned up and transported back into the cell by substances called ‘reuptake transporters’. 

When these transporters are too enthusiastic, or too slow and sloppy, we feel the effect of too much or too little of that neurotransmitter. 

Even if we have plenty of a particular neurotransmitter, if it’s cleaned up before it does it’s job, it’s the same as not having enough. 

It would be like an over-enthusiastic host clearing the table when you are part way through your meal. There’s plenty of food but not enough gets in your belly! 

How anti-depressants work 
An example of the significant way in which transporters can effect mood is evident from how anti-depressants work. 
Anti-depressant medication aims to inhibit, or calm down, serotonin reuptake. This is why the class of drug are called SSRI’s, Selective Serotonin Reuptake Inhibitors. 
These drugs increase the happy neurotransmitter, serotonin, not by making more of it, but by inhibiting its removal, thereby ensuring plenty is available to your neurons before it is transported away. 

About Methylation

Methlylation is the process of adding or donating methyl groups from one chemical, molecule or protein to another. It is a long and detailed chain of chemical events that is happening over and over inside you as you read this article. 
The methylation pathway is usually represented by a series of cogs and wheels creating interconnected cycles. Each wheel uses different enzymes and nutrients and each cog is dependent on the wheel before it operating effectively. 
Amongst many, many other things the methylation cycle governs gene expression. 

---

A little Snippet about SNPs 

Single Nucleotide polymorphism’s (SNPs) are little genetic abnormalities. They are very common and most don’t cause much, if any, trouble at all. In fact, most of us have up to 1000 SNPs (little genetic mutations) and we get along just fine. However, if the SNPs are in the methyl cycle, then depending on how many and in which area of the cycle, we can make too much or too little methyl. Either of these can cause  problems at the pointy end of us – our brain. 

Undermethylation 

If you are an 'undermethylator’ the genes that make your transporter proteins are not being switched off. You probably have several SNPs at important points in the cycle, so it tips toward not working up to speed. 
If too many genes are turned on (because they are not being turned off) neurotransmitter transporter production is increased this means less of the neurotransmitter is available at the gap. 

We need the neurotransmitter to hang around long enough to get the ‘message across’, just like we need the food left on the table long enough for us to eat our fill. 
At the neuronal level you are overproducing reuptake material and your key happy neurotransmitter, serotonin, is being swept away before it can do one of it's jobs, helping you feel okay

This explains, for example, why a person who is under-methylating is (sometimes but not always) prone to anxiety and/or depression. Serotonin creates our sense of well-being and peace in the world. 

Because the undermethylators issue is too much transporter material they usually respond well to antidepressants (SSRIs). SSRI medication counteracts the increase in transporters by blocking reuptake of serotonin.

Overmethylation 

Overmethylation is when the SNP or, in this case, a nutrient deficiency (folate) results in a lack of genes being turned on to make re-uptake transporters. 

So overmethylation is the opposite of undermethylation. One end's up with less neurotransmitter reuptake transporters and therefore more neurotransmitters hanging around overstimulating the cells and not getting recycled correctly. 
In this situation it is like we have a host that is forcing us to eat way beyond our limit. 

Overmethylation can result in too much dopamine and/or noradrenaline loitering in the synaptic gap. 

Noradrenaline can cause ongoing anxiety and in the extreme can drive obsessions and compulsions. 

 Dr Bill Walsh describes how anti-depressant medication can cause havoc with an overmethylator. This is due to the doubling-up effect of dampening serotonin reuptake. Overmethylators already have plenty of reuptake transporters, so inhibiting reuptake further with an SSRI creates a double-whammy with potential a massive overload of neurotransmitter. Dr Walsh proposes that the very few individuals who have strong adverse effects to SSRIs, even to the point of suicidal acts, are often over-methylators. 

Methylation works well for most 

Don’t be alarmed. Most people (around 70%) have no great problem in their methylation cycles. However, about 8% of the population over-methylate, and about 22% under-methylate. 

The hit-home message here is that of the 30% of people who have methylation issues, 70% will experience some form of psychological problem as a result. This  works out to be around 21% overall for whom methylation issues could be messing with their mental well-being. 

Symptoms of methylation issues 

Symptoms are not diagnostic or present in all, I have met highly motivated and inwardly competitive over methylators, and undermethylators with dry mouths and not hint of allergy. These are lists where one might only tick a few yet still have methylation issues, or may tick several boxes only to discover their methylation is just fine. 

Undermethylation 

• High achiever / High motivation
  
• Family history of high achievement 
  
• Self-motivated (can push self at school or university) 
  
• Competitive, if only internally (or externally in sport)
  
• Strong willed - can tend toward problems with authority figures or 'control freak" behaviour
  
• Tends to be non-compliant (especially and unfortunately with treatment!)
  
• ADHD / Oppositional Defiant Disorder
• Difficulty with transitions 
  
• High energy / High libido
  
• Addictive tendencies/ OCD tendencies 
  
• Calm demeanour - high inner tension
  
• Low pain tolerance 
  
• Don’t like the heat
  
• Seasonal/ inhalant allergies
  
• Can hear pulse in  head on the pillow at night
  
• Ruminations regarding past 
  
• Often slender 
  
• Good response to SSRIs (anti-depressants) or SAMe
  
• Tears up easily and plenty of saliva
  

Many high achievers are undermethylators, with high inner motivation they can reach great heights. Their ability to attend to details, organise themselves and others and be goal oriented can lead to a significant level of accomplishment. However, if afflicted by an underlying depression or anxiety their drive can manifest in never feeling satisfied with (or even completing) their last project so they keep moving toward the next goal. 
The extreme negative manifestation can lead to the development of controlling behaviour, obsessive / compulsive traits and addictions.
Children can be A students or divert their strong will into oppositional-defiant type behaviour rebelling against authority. 
Teens can channel their drive toward computer gaming, drugs and alcohol, eating or dating.

Overmethylation 

• Low achiever / non competitive
  
• Poor motivation (regardless of intelligence)
  
• Creative - Artistic or musical ability 
  
• Often kind and 'selfless' in actions
• Nervousness, High anxiety - tendency to panic
  
• Nervous legs / pacing 
  
• Can be hyperactive / ADHD
  
• Low libido / low energy
  
• More likely to be overweight 
  
• Easily frustrated 
  
• Difficulty sleeping soundly
• High pain threshold (check your head bangers)
  
• Tendency to food or chemical sensitivity 
  
• But little or no seasonal allergies

• Eczema/dry skin
• Dry eyes and mouth 
• Depression 
  
• Self-isolation, may prefer own company    
• Tinnitis 
• Adverse response to SSRIs

The overmethylator is motivated by the opposite characteristics of an undermethylator. Where the undermethylator can be driven to success the  overmethylator is not motivated by being better than others, their compassionate and kind nature allows them to easily put others' needs ahead of their own.  They may succeed as great musicians or designers or fit comfortably into service roles in nursing or health care. 
However, given their sensitivity and other-orientedness they may also be hurt more deeply by the the insults of life, dwelling on things and perpetuating their inner tension or anxiety. They grapple to understand the injustice of others and tend to blame themselves for any unkind actions of others toward them. 
Children may display their high inner tension in hyperactivity or become overwhelmed by anxiety.
Teens may struggle with low motivation and depression and sensitivity to unfairness and perceived rejection.

Treatment 

I won’t go into treatment in too much detail, because you really need to see a specially trained health practitioner for treatment. However, having come this far I do feel I need to tell you a couple of things. 

One is that what is good for an undermethylator is NOT good for an overmethylator. 

Undermethylators usually do okay on SSRIs and SAMe, whereas overmethylators will not. Overmethylators need more folate (and niacin) to bind the excess methyl groups, undermethylators often find they feel worse on folate or folic acid. 
Please see an appropriately trained Health Practitioner to treat any issues that you think you may have. You don’t want to incorrectly mess with the methylation cycle! 

Histamine Hints at Methylation Status 

There are other ways that more accurately measure methylation, but  the most commonly used, “quick and dirty”, measure of methylation status - measuring whole blood histamine levels.

If histamine is within normal range (0.45- 0.5. or 48-60), it can indicate methylation is working okay. A high histamine level (>0.6 or 70) could mean you are an undermethylator and low histamine level (<0.35 or 48) could indicate you are an overmethylator. 

*If you are getting a whole blood histamine test to assess methylation remember not to take any anti-histamine medications for 10 days prior to testing as these will mess up the results.

---

Last mouthful 
As you may have gleaned, there is always a balancing act going on between all the various aspect of physiological functioning. The effects of too much or too little methylation on neurotransmitter levels may not show up for a long time, if at all. OR, depending on what else is going on in the person’s life, body, genetics, etc. the effects of faulty methylation may manifest in a mood disorder or significant mental illness. As always the effect of life events, personal history, stress  and personality can not be separated from current mental state. 

References 
William J Walsh, Nutrient Power
Dr Menash, Presentation http://www.mensahmedical.com/resourcecenter.html
Dr. A.T. Lewis, http://www.integrativepediatricsofohio.com