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FROM MOOD DISORDERS TO MCS: A NEUROINFLAMMATORY MODEL

jeffrez

Senior Member
Messages
1,112
Location
NY
Very interesting article, thanks. Imho, it is possible in some cases to turn this supposed neuroinflammation "off," resulting in global amelioration of symptoms, but the question is how exactly to do it. I would think long term meditation might have that effect, but I know that a number of people with CFS meditate without remitting. Maybe the amygdala retraining could have that effect, too, IDK but it seems plausible.

Nice telecaster, too. :- )
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Very interesting article, thanks. Imho, it is possible in some cases to turn this supposed neuroinflammation "off," resulting in global amelioration of symptoms, but the question is how exactly to do it. I would think long term meditation might have that effect, but I know that a number of people with CFS meditate without remitting. Maybe the amygdala retraining could have that effect, too, IDK but it seems plausible.

Nice telecaster, too. :- )

Excuse me. Its a '51 Nocaster.;)

But thanks for the comments.

I'll be discussing theoretical treatments in due course. Theoretical of course because I'm in no way medically qualified.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
PS - If you have any comments - positive or negative - please post there.

I intentionally 'blogged' this to run it past the ME/CFS community to see if it resonated rather than write it up formally and submit it to something like Medical Hypotheses where it would be comprehensively ignored by the mainstream. If I'm well 'off beam' I'd like to know.

BTW jeffrez - you're obviously a connoisseur of fine guitars.
 

jeffrez

Senior Member
Messages
1,112
Location
NY
Haha, I do like teles / 'casters. ;-) Especially with the neck HB. Don't have the budget to be a real connoisseur, but it's nice to dream. :- ) If that's yours, it's a beauty, and must be worth quite a lot.
 

A.B.

Senior Member
Messages
3,780
This would complement the mercury hypothesis. Mercury can cause neurotoxicity via glutamate release even at levels that would be not be considered toxic. Glutamate is the excitatory counterpart to inhibitory GABA. Mercury is also linked to many of the biochemical abnormalities mentioned in the article and persists for decades in the brain after oxidation to Hg++.

It is plausible that individuals with reduced ability to excrete mercury could gradually build up harmful levels in their brain.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Haha, I do like teles / 'casters. ;-) Especially with the neck HB. Don't have the budget to be a real connoisseur, but it's nice to dream. :- ) If that's yours, it's a beauty, and must be worth quite a lot.

Not an original jeffrez - a Fender Custom Shop relic - still pricey but its not as if I spend my money on parties and holidays these days!

Glad you like it:)

PS - It may seem trivial but I've been playing guitar on and off since 16 year old - a few years before ME/CFS. Its something I can identify with that's not defined by illness. In the same way I still hold on to my now 30 year old squash racquet - its not that I expect to,play again - its more that I refuse to be purely defined by this illness.

Hence the avatar. Sorry for the rant!
 

warriorseekspeace

Senior Member
Messages
141
Location
Florida
Please, Marco, and AB, if you know anything that might help me. My brain is going quickly. I think what you wrote about astrocyte swelling resonates with me. Are there glutamate inhibitors I can take?? My muscles are not tense however, rather, my core/ spinal muscles are very weak and low tone.

Your first article on glutamate resonated so strongly with me, too, that I emailed it to a doctor of mine, to ask about a medication you mentioned is not yet used in the US i think though.

I am also having mercury amalgams removed, and am down to one left (this being done only because I had decay around them all anyway. I have the next one out in a week and a half.

I have lots else going on, too. Thought I was getting better, but tremendous confusion again.
Is there anything I can take, or do? I take befotiamine, among many many other things.

I will see a psychiatrist Monday (urgh, hate it, but have to, to get anything to help with sleep, for which i take prescription antihistamines. I will not take anything addictive or mood altering, as I am sixteen years in recovery, and must never become addicted to anything again.
HE put me on low dose lithium for its neurotrophic properties, he said. I added lithium orotate. Anyway, is there anything I could ask him for that might help with these symptoms. He is pretty cool, even asked for the IACFSME primer for other severely fatigued patients. He likes to help HIV patients, for instance, too.
Thanks,
WaSP
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Please, Marco, and AB, if you know anything that might help me. My brain is going quickly. I think what you wrote about astrocyte swelling resonates with me. Are there glutamate inhibitors I can take?? My muscles are not tense however, rather, my core/ spinal muscles are very weak and low tone.

Your first article on glutamate resonated so strongly with me, too, that I emailed it to a doctor of mine, to ask about a medication you mentioned is not yet used in the US i think though.

I am also having mercury amalgams removed, and am down to one left (this being done only because I had decay around them all anyway. I have the next one out in a week and a half.

I have lots else going on, too. Thought I was getting better, but tremendous confusion again.
Is there anything I can take, or do? I take befotiamine, among many many other things.

I will see a psychiatrist Monday (urgh, hate it, but have to, to get anything to help with sleep, for which i take prescription antihistamines. I will not take anything addictive or mood altering, as I am sixteen years in recovery, and must never become addicted to anything again.
HE put me on low dose lithium for its neurotrophic properties, he said. I added lithium orotate. Anyway, is there anything I could ask him for that might help with these symptoms. He is pretty cool, even asked for the IACFSME primer for other severely fatigued patients. He likes to help HIV patients, for instance, too.
Thanks,
WaSP

Hi WasP

Sounds as if you're in bad way at the moment.

I'm in no way qualified to give medical advice and as you say most if not all gabaergic drugs have issues with tolerance and dependency plus the potential for some pretty severe problems on withdrawal.

There may be some self help things you might try that won't be a cure but might give some relief. As jeffrez said regular meditation (mindfulness) has been shown to raise GABA levels. It might also help to keep an eye on your diet - avoiding any pre-prepared meals that might contain excitotoxins and trying to avoid food ingredients with too much free glutamate (like cooked tomatoes). Gabaergic l-theanine/green tea supplements might be worth trying if you haven't already.

One thing that I find helpful is n-acetylcysteine which is a powerful anti-oxidant and glutamate antagonist which has shown positive effects in some of the 'psychiatric' illnesses associated with neuroinflammation :

The therapeutic role of adjuvant antioxidants (for example, vitamins C and E) in psychiatric disorder remains to be substantiated by high-powered randomized clinical trials. N-acetylcysteine shows the most promising results to-date, with several randomized placebo-controlled trials demonstrating its efficacy in MDD, BPD and schizophrenia.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626880/

(I wouldn't try reading this if you have cognitive problems but your psychiatrist may be interested)

Befotiamine sounds like a good idea if you suspect neuropathies.

Apart from that your psychiatrist sounds like a reasonable guy and is the best source of advice on what may or may not help. Perhaps you should mention that you suspect that a glut/GABA imbalance may be contributing to your symptoms and also your concerns about addictive of mood altering drugs and see what he suggests?

Hope that helps.
 

A.B.

Senior Member
Messages
3,780
Please, Marco, and AB, if you know anything that might help me. My brain is going quickly. I think what you wrote about astrocyte swelling resonates with me. Are there glutamate inhibitors I can take?? My muscles are not tense however, rather, my core/ spinal muscles are very weak and low tone.

Your first article on glutamate resonated so strongly with me, too, that I emailed it to a doctor of mine, to ask about a medication you mentioned is not yet used in the US i think though.

I am also having mercury amalgams removed, and am down to one left (this being done only because I had decay around them all anyway. I have the next one out in a week and a half.

You can take a selenium supplement if you believe that mercury may be involved in your health problems. There is some evidence that selenium protects against mercury toxicity by forming stable complexes with it. There is also a study which reported a correlation between low selenium levels in blood and claims of amalgam filling related health problems (link). There are unfortunately no useful lab tests that one could perform to clarify the the situation in regards to brain levels of mercury, so it's all speculation and guessing.

The herbal supplement Ashwagandha could be worth trying for its GABA-like effect (link).

Personally I saw ~90% reduction in certain "psychiatric" symptoms after amalgam removal, but no improvement in fatigue and physical symptoms.
 
Messages
15,786
Please, Marco, and AB, if you know anything that might help me. My brain is going quickly. I think what you wrote about astrocyte swelling resonates with me. Are there glutamate inhibitors I can take?? My muscles are not tense however, rather, my core/ spinal muscles are very weak and low tone.
I strongly agree with what Marco said regarding NAC. I had big problems with my mind never shutting down, and 1800mg per day is helping me a lot with that. I take the sustained-release version, so it theoretically gets absorbed more slowly. I take my last dose shortly before bed, and it gets me through the night. If I forget a dose, then I notice the effects pretty quickly. As a side effect, you should be creating some more glutathione.

Some people need both NAC and glycine to lower glutamate.

I also avoid MSG (monosodium glutamate) like the plague. This means eating home cooked unprocessed foods for the most part. Manufacturers use a ton of different names to hide it, and even "natural flavors" must be considered suspect.
 

Enid

Senior Member
Messages
3,309
Location
UK
Mood disorders - wish I could have started that way instead of collapsing in the street., This has to be a bad joke Marco and Cort - a nothing better to do and diversion. "Mood disorders" belong where every ordinary person has sussed out as the failure of science.
 

warriorseekspeace

Senior Member
Messages
141
Location
Florida
Yes, yes, yes! Thanks to all so much. OK. I am on right track. Have all of the above in cabinet, and/or was taking on/off. Now am going to water therapy then back injections; will reply more later; so grateful!
P.S. Is there any reason NOT to take the NAC until after the last amalgam is out? I was waiting until then, but cannot remember why. Perhaps was confusing it with what I read in my quick crash-course reading here and there in a fog, about not taking chelators, like ALA, while mercury still in mouth??? (Since I have the same asparagus smell in pee after taking either ALA or NAC, I probably lumped them together, lol. I really do not understand any of this stuff at a chemistry level.)
BEst wishes.
WaSP
 
Messages
73
Location
Belgium
I also avoid MSG (monosodium glutamate) like the plague. This means eating home cooked unprocessed foods for the most part. Manufacturers use a ton of different names to hide it, and even "natural flavors" must be considered suspect.[/quote]

There's an article on pubmed about MSG and fibro.
BACKGROUND:

Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively.
CASE SUMMARY:

Four patients diagnosed with fibromyalgia syndrome for two to 17 years are described. All had undergone multiple treatment modalities with limited success. All had complete, or nearly complete, resolution of their symptoms within months after eliminating monosodium glutamate (MSG) or MSG plus aspartame from their diet. All patients were women with multiple comorbidities prior to elimination of MSG. All have had recurrence of symptoms whenever MSG is ingested.
DISCUSSION:

Excitotoxins are molecules, such as MSG and aspartate, that act as excitatory neurotransmitters, and can lead to neurotoxicity when used in excess. We propose that these four patients may represent a subset of fibromyalgia syndrome that is induced or exacerbated by excitotoxins or, alternatively, may comprise an excitotoxin syndrome that is similar to fibromyalgia. We suggest that identification of similar patients and research with larger numbers of patients must be performed before definitive conclusions can be made.
CONCLUSIONS:

The elimination of MSG and other excitotoxins from the diets of patients with fibromyalgia offers a benign treatment option that has the potential for dramatic results in a subset of patients.

Marco, I don't know if you're familiar with Dr. Jay Goldsteins theory, but it's largely based on NMDA (main glutamate receptor) receptor overactivity. You might find it interesting.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Mood disorders - wish I could have started that way instead of collapsing in the street., This has to be a bad joke Marco and Cort - a nothing better to do and diversion.

Enid you surprise me after liking what I posted on primary biliary cirrhosis (which as you know is very much a physical autoimmune disorder) :

This dysregulation may directly or indirectly influence sick behaviours, as the enhanced release of TNF-α within the brain contributes to the development of mood disorders and mental sickness [3036].

I do a lot of collapsing myself but did have (depression - not any more) and do have (anxiety) symptoms that would be classed as 'mood disorders'. Neuroinflammation doesn't discriminate as to which brain areas are affected and I would expect us all to have a different mix of symptoms.

No intention to trivialise or offend:) . I thought I'd pretty much dismissed these symptoms up front as what you'd expect in a neurological disease.
 

Enid

Senior Member
Messages
3,309
Location
UK
Let us not be surprised Marco - my brother's (Prof Neurology) has moved to autoimmune - liver etc involved. All I am saying is that basic medicine (most especially here UK) has and does miss the basic infection - basic crash of the Immune system and all that follows. Encephalitis in my case for starters (but don't tell the psyches).
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Marco, I don't know if you're familiar with Dr. Jay Goldsteins theory, but it's largely based on NMDA (main glutamate receptor) receptor overactivity. You might find it interesting.

I mentioned Goldstein in my first blog in the series : http://www.cortjohnson.org/blog/201...xplain-chronic-fatigue-syndrome-mecfs-better/

.... as he suspected that MECFS patients might have a problem with gating out sensory information. Unfortunately, as stated in the blog, he doesn't appear to have tested this theory.

Needless to say I agree with him!
 

Enid

Senior Member
Messages
3,309
Location
UK
"Gating" is indeed a problem and has been long known in ME - otherwise known as too much incoming information to process - now when will science/medicine find the pathology affecting cognitive processing.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I found an article on a similar subject. It talks about inflammation, glutamate, and glia (both microglia and astroglia) and their role in depression:
http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1590
Inflammation, Glutamate, and Glia in Depression: A Literature Review
Abstract
Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-α treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.
Introduction
Depression is a common and debilitating disorder for which current treatments are inadequate. The pathogenesis of depression is not well understood. The annual prevalence of depression is 7% and the lifetime prevalence is 16%.1,2 In addition to significant disability,3depression is associated with excess mortality,4,5 particularly from cardiovascular disease.6 Current antidepressants, which target monoamines, only produce remission in 30% of patients. Part of the problem lies in the fact that the pathophysiology of depression has not been elucidated, and treatments are based on empirical data, not mechanisms of action. It remains unclear how these drugs actually work, since their ability to increase synaptic concentrations of monoamines is immediate, while their clinical effects take 2–4 weeks to become apparent.7 The aim of this article is to provide an overview of studies implicating inflammation in depression, and propose a model of how excess inflammation may interact with glutamate and glia to cause depression.