Hi Tom,
For newer folks to this arena, I would like to first clarify the terminology of undermethylated vs. overmethylation. This is a particular occurence having to do with methyl donors and their effects due to not enough or too many methyl donors in those with mutations within the methylation cycle. With some mutations, one may find they cannot tolerate larger quantities of methyl donors, and in others, one may find they are indeed in need of many sources of methyl donors.
Tolerance to methyl donors is referenced by Yasko, and determined to be centered around COMT status. COMT +/+ is a downregulation, in that +/+ is sluggish essentially slowing the methylation of brain neurotransmitters (this mutation will not break down the neurotransmitters as efficiently). The COMT enzyme uses methyl groups to help inactivate dopamine and nor-epi. Since a +/+ is a downregulation, then this particular individual may not be using up methyl groups, since it slows down methylation at this particular point, and so they wouldn't tolerate the addition of methyl groups like a -/- or a +/-. And a +/- not as much as a -/-. Excess methyl groups or the terminology, "overmethylation" would then equate to erratic behaviour, mood swings, hyperactivity, and irritability.
-/- individuals will deplete methyl donors and can tolerate more methyl donors.
COMT is involved in the breakdown of dopamine as well as nor-epi and also estrogen, and pain tolerance.
Dopamine: Is a neuotransmitter linked to motor/movement disorders, ADHD, addictions, paranoia, and schizophrenia. It strongly influences both motor and thinking areas of the brain.
Low levels are associated with muscle stiffness, stooped/unstable posture, loss of balance/coordination, gait disturbances, tremors, fixed, mask like expressions, slow speech, impaired fine motor skills, falling when walking, and impaired cognition. Low levels would impair the ability to focus or lock on to tasks, activities, or conversations.
As dopamine levels rise, we would become energized and excited, then suspicious and paranoid, and then finally hyperstimulated by the environment.
Nor-Epinephrine (Nor-epi): Is a neurotransmitter associated with the fight or flight response. Mood swings, anxiety, and depression are related to nor-epi levels, as it is this neurotransmitter that maintains the balance between agitation and depression. Because it is strongly involved in physical reactions, moderate increases create worry, increased startle reflex, jumpiness, fear of crowds and tight places, impaired concentration, restless sleep, rapid fatigue, muscle tension/cramps, irritability, and a sense of being on edge. Panic attacks are sudden and severe increases in nor-epi.
So in the context of this entire conversation and your particular COMT status +/-, and remember, +/+ is a downregulation, you may very well have elevated levels of these neurotransmitters, but that is not accounting for the combination of mutations, just this single particular one.
Vitamin D receptors or VDR bsm-taq also relate to dopamine and nor-epi levels. Vitamin D increases the enzyme involved in synthesizing these. I believe the VDR bsm-taq can compensate for COMT mutations as from what I have read, vitamin D levels correlate directly with dopamine levels ( ^ levels of Vitamin D = ^ levels of dopamine). Sensitivity to methyl donors are equated to individuals in which have higher levels of dopamine. Higher levels of these neurotransmitters are equated to -/- individuals. You have a +/+ mutation which is thought to be equated to lower levels of Vitamin D, and thus lower levels of the enzyme involved in synthesizing these neurotransmitters. These could very well compensate for each other in your case. The fact that you are having trouble would then justify investigation into bacterial and toxic metals in your case, in which could very well lead to the experiences you are describing.
Something of addittional interest to you, in the book, Genetic Bypass, by Dr. Amy Yasko...
...The nutrigenomics report for this individual shows a single mutation in the COMT gene. This means that this individual should be able to tolerate more methyl donors than individuals who are COMT +/+, but it will still be important to watch the total number of methyl donors used in supplementation. The COMT +/- indicates they will break down dopamine more rapidly than a COMT +/+ and as such will be depleting methyl groups from their methylation cycle as well, although not to the extent of COMT -/- individuals.
This individual is also VDR bsm-taq +/+. What this may mean is that because this individual is COMT +/- and VDR bsm-taq +/+, they will behave like a COMT -/- individual in terms of their responses to most methyl donors and may need added methyl donors for optimal dopamine and other methyl balance in the body.
There is also a mutation in the MTRR gene. What this means in practical terms is the they may be deficient in methyl B12. The function of MTRR is to regenerate B12 for the methionine synthase to use. Due to this individuals COMT and VDR bsm-taq status, they should need and will tolerate the addition of methyl containing supplements.....If mood swings occur, decrease the amount of methyl B12 to a more comfortable level.
MAO-A: (personally I think this one should be renamed to something more derogatory like the MTHFR enzyme is to some.)
And of which you also seem to be blessed with a single point mutation in the A1298C incidently. But I digress for the moment....
Again, MAO-A: This is the warrior mutation and is involved in the breakdown of Serotonin. This is the bliss to despair neurotransmitter and has been identified in multiple pyschiatric disorders including depression, OCD, anorexia, bulemia, body dysmorphia, social anxiety, and phobia's. It is involved in processes such as sleep, libido, and body temperature.
When serotonin is low, we experience problems with concentration and attention. We can become scatterbrained, and poorly organized. Routine responsibilities will seem overwhelming. We lose our car keys, and put odd things in the refrigerator. (Personally, I have put the peanut butter in the fridge and the milk in the cupboard..
) When we are driving, we forget where we were going, when we call someone, we forget why we called them in the first place, when we go grocery shopping, we forget the list, or forget what we needed in the first place. We also tell people the same thing two or three times.
As serotonin levels decrease, we can become more depressed. At moderately low levels, major changes in bodily functions can occur. Such as...
Chronic Fatigue. Despite sleeping extra hours and naps, we remain tired.
Sleep disturbances, can't get to sleep or early morning waking and then can't fall back asleep.
Appetite disturbances. Either a loss of appetite and weight loss, or weight gain due to the bodies craving for carbs in an attempt to make more serotonin.
Loss of sexual interest, loss of interest in general.
Social withdrawal is common, not answering the phone, rarely leaving the house, stop calling friends and family, and withdrawal from social activities.
Emotional sadness and frequent crying spells are common.
Self-esteem and self-confidence is low.
Body sensations, due to serotonins role as a body regulator, include hot flashes, and temp changes, headaches, and stomach aches.
Outbursts will begin. Typically two types. Crying and behavioral.
Thinking speed will increase.
Memory torture. Your brain at 100 mph, will search your memories for your most traumatic or unpleasant experiences. You will suddenly become pre-occupied with horrible experiences that may have happened ten, twenty, or even thirty years ago. You will relive the death of loved ones, divorce, child abuse, whatever the brain can find to torture you with, and you will feel as though it happened yesterday.
Loss of personality, a sense that our sense of humor has got up and left us, personality changes.
And we begin taking everything very personally. Comments, glances, and situation are viewed personally and negatively. If someone talks to you, it irritates you, and it irritates you if they don't and become angry because you are ignored.
This is the neurotransmitter in which your family will notice first, in that your behavior is odd, or have the sense that you have faded away. You talk less, smile less.
Very low levels will bring this particular individual to the attentions of others, doctors, etc. Severe depletion also affects the brains ideation/thinking, and becomes very uncomfortable and even torturing in thoughts. Symptoms are very difficult to ignore by others. When you reach the bottom of the severely low, the "garbage truck" will arrive. Everyone with severely low levels will experience family members telling them they are a bad spouse, husband, wife, daughter, son, employee, etc.
The other end of this spectrum is too high levels of serotonin. This is called serotonin syndrome.
I have had the extreme pleasure of experiencing both sides of this neurotransmitter. MAO-A + is a decreased enzyme activity mutation and many with this will experience cycle fluctuations in serotonin. There for experiencing both sides of it. This cycling from low to high levels results in extreme mood swings and/or aggressive behaviors (where the "warrior" term was coined). Again, infections can deplete tryptophan, and also affect MAO-A status. A double whammy if you like and hence why I think it needs to be renamed....
More on next post.....
