Apologies in advance; this thread should be of general interest, but it is, shall we say, inspired by personal experiences. In brief, it's been a rough 15 months. I decided to put any gory details and lengthy symptom lists in spoilers so you can cut to the chase if you like.
Anyway, I'm in a ... temporarily adequate, shall we say ... place now, mentally speaking, though there are some persistent physical and cognitive symptoms that at first seemed unrelated but, upon reflection, actually could all be tied to deficits in cholinergic transmission. And that's the point of this thread.
I ran across this paper which suggests an acute trauma may induce chronic changes in acetylcholine expression:
Acute stress facilitates long-lasting changes in cholinergic gene expression
I haven't read the full text, but they imply that the surge in acetycholine that occurs during acute stress (perhaps this is the cause of "life flashing before one's eyes"??) leads to epigenetic changes leaving one in a chronically hyperexcitable state. However, they associate these symptoms with AChE inhibitors, i.e. a surplus of ACh.
Now, I dunno about that, but Wikipedia lists the following as anticholinergic side effects:
Some additional symptoms that may be anticholinergic in nature:
So I've got all these symptoms, and a lot of other people have some or all these symptoms (and some I don't) associated with diverse chronic conditions such as
- CFS/ME
- The morass known as "Adrenal fatigue"
- Post acute benzodiazepine withdrawal
- Chronic Lyme
- Gulf War Syndrome
- PTSD
- MG, Sjogren's, other autoimmune diseases
- More?
Could it be so simple that so many symptoms of chronic conditions arise as a malfunction of the longest-known neurotransmitter -- a sort of hyperactive sympathetic and anemic parasympathetic nervous system? Or perhaps even stress-induced autoantibodies, a sort of functional myasthenia gravis? I'm guessing no, but still ... cofactors such as B5 are popular in adrenal fatigue treatment, and B1 megadoses have a decent response rate in CFS/ME.
There may be a genetic component. For instance, my mother and her sister have had many of these symptoms since their mid 40s. Of possible relevance, I'm homozygous for COMT V158M, COMT H62H, and MAO-A R297R, which means lots of dopamine with impaired neurotransmitter breakdown. People with that genotype are particularly susceptible to chronic stress. Oopsie.
OK, so IF this mechanism is correct, what are the possible treatment options? Here's what I can think of, in ascending quality:
1) ACh agonists. I don't know if AChR are susceptible to the same downregulation as other receptors, but presumably they are, so this isn't a great option
2) AChE inhibitors. Ditto to 1. Blunt instrument approach
3) Supply abundant precursors, magnesium, thiamine / benfotiamine / sulbutiamine / allithiamine, pantothenic acid / pantethine, and a choline source. Let the body make what it needs. I don't know that this would work, as from personal experience I already get plenty of these in my diet (and furthermore supplement thiamine to make up for possible depletion from booze). Also may lead to downregulation. Nevertheless, I may try a megadose protocol and report back. A doc was able to treat 30% of stutterers with such a protocol.
4) Vagus nerve stimulation may help, if sufficient ACh is actually available
5) Find a way to upregulate / rebalance cholinergic receptors. Not sure exactly how.
6) Increase BDNF to generally restore neuroplasticity. There are a variety of ways to do this. Still, TrKB downregulation is an issue.
7) Restore proper cortisol homeostasis and hopefully the cholinergic system will follow suit.
If anyone knows more about the cholinergic system and stress, please chime in. Any other thoughts or comments are welcome also.
Personally, I think I'm going to finally dig into that pile of NSI-189 that's been sitting around for a couple months really soon.
Edit: added PTSD.
Edited by StevesPetRat, 13 October 2014 - 08:23 AM.