Disclaimer: This information is presented for descriptive purposes only. It is in no way intended for diagnosis or treatment. It comes from my own research and reading on the subject. Individuals should always do their own research and seek advice from an appropriately trained professional.
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.
Here is a more detailed but still very simplified explanation of how Methylation can affect our mental and emotional states.
For information to be transmitted between two cells a little squirt of neurotransmitter (chemical messenger) leaves the end of one cell, and, if everything goes 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 its original cell. There are several different types of neurotransmitters that perform different functions and create many different moods.
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 its job, it’s the same as not having enough.
Think of this as 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:
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 its 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.
Overmethylation is a case of having too many methyl groups. So when the SNP relates to a nutrient deficiency (folate), this results in a lack of genes being turned on to make re-uptake transporters. The end product is an oversupply of serotonin, dopamine and noradrenaline.
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.
Excess serotonin does not make one happier--it hypes you up (see Serotonin Syndrome research). However, the issues overmethylators experience are more likely related to excess noradrenaline (norepinephrine), often to the point of suffering a constant feeling of anxiety or unease.
Because the undermethylator's 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.
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 for a massive overload of neurotransmitters. 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.