Hypothalamic Dysfunction Theory + studies

[Ali_Mardiyev]

Hello everyone. My name is Ali. I'm 20 years old. I got ME/CFS 4 months ago, and have been researching since.
I have created this thread to support my theory on hypothalamic dysfunction causing all of our symptoms/dysregulations.
I plan to cite studies and articles to further explain/support my theory.
Obviously, I'm pretty knew to this and I will for sure make a lot of mistakes. That's the exact reason I created this thread. For more knowledgeable people to look through, analyze, complete and make remarks to my theory.
Any opinion would be appreciated! 🙏

Another thread to describe your symptoms:
https://forums.phoenixrising.me/threads/everyone-share-your-symptoms.89227/

 

[Ali_Mardiyev]

1. Hypothalamus and our symptoms

https://my.clevelandclinic.org/health/articles/22566-. Hypothalamus and its role in homeostasis

https://webspace.ship.edu/cgboer/limbicsystem.html The "limbic" system and autonomic function

https://www.flintrehab.com/hypothalamus-brain-injury/ Hypothalamic damage symptoms

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157417/ Hypothalamus and mytochondria

https://www.frontiersin.org/articles/10.3389/fnins.2017.00703/ Hypothalamus and MCAS, particularly CRH(corticotropin releasing hormone) activating glial and mast cells, which cause neuroinflammation.

 

[Ali_Mardiyev]

2. Circadian rhythm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931002/ Circadian rhythm and the hypothalamus. The SCN's role in controlling the circadian rhythm. An important role of the CLOCK(BMAL1) gene-transcription factor.

https://www.pnas.org/doi/10.1073/pnas.0906361106 Circadian rhythm and immunity

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729855/ Interesting study on mice.

 

[Ali_Mardiyev]

3. Dopamine deficiency

Some of our symptoms are similar to Parkinson's and Alzheimer's disease, and I think are caused by low dopamine or dopamine receptor downregulation and glutamate toxicity.
This explains why LDA, LDN, pramipexole, memantine and several other drugs have such an effect.

The hypothalamus in Parkinson Disease
Frontiers
www.frontiersin.org

Molecular Mechanisms of Glutamate Toxicity in Parkinson's Disease
ncbi.nlm.nih.gov
https://www.ncbi.nlm.nih.gov › pmc

Dopamine and Dopamine Receptors in Alzheimer's Disease - NCBI
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791143/

 

[Violeta]

You are very good at organization and your links are very interesting. Thank you for sharing your research.

 

[Ali_Mardiyev]

Dopamine's effect on th1 cells. This can partly explain, why dopaminergic drugs work on CFS/ME
https://www.google.com/url?sa=t&sou...oQFnoECBYQAQ&usg=AOvVaw2TT2p-LKbJ6OquzaRCObMH

 

[Rufous McKinney]

This explains why LDA, LDN, pramipexole, memantine and several other drugs have such an effect.

curious if you have an opinion about nootropics like Modafinil (aka Provigil) ? (my doctor wants me to take 50 mg lo dose)

Its sometimes prescribed to ME patients with cognitive issues.


Online its described like this:

Is modafinil a dopamine reuptake inhibitor?


Modafinil and its biologically active r-isomer, armodafinil, are approved for treatment of excessive sleepiness in narcolepsy in adults. These agents are believed to be dopamine reuptake inhibitors and affect alpha-adrenergic, serotonergic, and GABA pathways (Dauvilliers, et al., 2007; Mignot, 2012; Lecendreux, 2014).

(the SSRI's cause me to get profoundly ill and I can't tolerate it)


Also online:

So not only does [Provigil] increase dopamine in the human brain, but does it by similar mechanisms to Ritalin and cocaine, by directly blocking the dopamine transporter. It is not working by some distinct, different mechanism." Volkow notes that Provigil has no effect on mice lacking dopamine transporters.

You seem to know alot about this topic so I am curious if you might have a more informed opinion about its use.

 

[Violeta]

Dopamine's effect on th1 cells. This can partly explain, why dopaminergic drugs work on CFS/ME
https://www.google.com/url?sa=t&sou...oQFnoECBYQAQ&usg=AOvVaw2TT2p-LKbJ6OquzaRCObMH

That's so interesting, and led me to this study.

Immunomodulatory Effects of Dopamine in Inflammatory Diseases

https://pubmed.ncbi.nlm.nih.gov/33897712/

Edit in:
Recently, the role of the DA receptor in inflammation has been widely studied, mainly focusing on NLRP3 inflammasome,

"With detailed descriptions of their roles in Parkinson disease, .......rheumatoid arthritis,"

I have intermittently had rheumatoid arthritis symptoms, and have had it again for the past two weeks. So when I saw "rheumatoid arthritis" in the study about the DA receptor along with NLRP3, (which I had been meaning to look into at greater depth), and also rereading "Uric Acid as a Factor in the Causation of Disease" because of it's view on RA, I looked up uric acid plus NLRP3 and found this.

I didn't expect to find it because when you look up NLRP3 you see that it's mostly talked about in relation to viruses.

Soluble Uric Acid Activates the NLRP3 Inflammasome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233987/

 

[Rufous McKinney]

Another substance that came up recently was:

Guanfacine- when combined with NAC, this is supposedly benefit focus and attention ADHD and something was published last week about taking it for long covid brain fog.

My GP did not sound very excited about the idea of taking anything like that. But we did not discuss in detail.

Info about that study here:

https://www.healthrising.org/blog/2022/12/24/brain-fog-long-covid-chronic-fatigue-fibromyalgia/

 

[Ali_Mardiyev]

curious if you have an opinion about nootropics like Modafinil (aka Provigil) ? (my doctor wants me to take 50 mg lo dose)

Its sometimes prescribed to ME patients with cognitive issues.


Online its described like this:

Is modafinil a dopamine reuptake inhibitor?


Modafinil and its biologically active r-isomer, armodafinil, are approved for treatment of excessive sleepiness in narcolepsy in adults. These agents are believed to be dopamine reuptake inhibitors and affect alpha-adrenergic, serotonergic, and GABA pathways (Dauvilliers, et al., 2007; Mignot, 2012; Lecendreux, 2014).

(the SSRI's cause me to get profoundly ill and I can't tolerate it)


Also online:

So not only does [Provigil] increase dopamine in the human brain, but does it by similar mechanisms to Ritalin and cocaine, by directly blocking the dopamine transporter. It is not working by some distinct, different mechanism." Volkow notes that Provigil has no effect on mice lacking dopamine transporters.

You seem to know alot about this topic so I am curious if you might have a more informed opinion about its use.

It also has certain anti-inflammatory effects
See this study: https://www.google.com/url?sa=t&sou...8QFnoECBcQAQ&usg=AOvVaw2SlLNdWmi16Xh5f3XWkVqH

I don't know the particular reason for you taking it, although it will help with cognitive issues, atleast temporarily. Starting with a low dose is a good idea.

However I'm a proponent of increasing dopamine receptor sensitivity, mostly because I'm sure that's my problem, and maybe of some other people's too. I plan to start taking LDA(low dose abilify), I believe it can help(possibly bring remission) if taken in low dosages:
https://forums.phoenixrising.me/members/nolongerdiseased.45407/

 

[Ali_Mardiyev]

Another substance that came up recently was:

Guanfacine- when combined with NAC, this is supposedly benefit focus and attention ADHD and something was published last week about taking it for long covid brain fog.

My GP did not sound very excited about the idea of taking anything like that. But we did not discuss in detail.

Info about that study here:

https://www.healthrising.org/blog/2022/12/24/brain-fog-long-covid-chronic-fatigue-fibromyalgia/

I honestly thing it's milder than modafinil, though I don't know much about it. It does lower blood pressure, so it's a double edge sword depending on your particular situation.
Can also cause mild insomnia, but that's pretty much all dopaminergic drugs, so I wouldn't worry too much about it

 

[Ali_Mardiyev]

That's so interesting, and led me to this study.

Immunomodulatory Effects of Dopamine in Inflammatory Diseases

https://pubmed.ncbi.nlm.nih.gov/33897712/

I'm currently heavily researching on the effects of dopamine on immunity, and how it's related to Th1/Th2 cells.
This girl went into remission using LDA, which is a dopamine agonist https://forums.phoenixrising.me/members/nolongerdiseased.45407/

Can I ask you a question: do you also rarely get "normal people" sick? It's a common denominator among ME/CFS sufferers

 

[Violeta]

I'm currently heavily researching on the effects of dopamine on immunity, and how it's related to Th1/Th2 cells.
This girl went into remission using LDA, which is a dopamine agonist https://forums.phoenixrising.me/members/nolongerdiseased.45407/

Can I ask you a question: do you also rarely get "normal people" sick? It's a common denominator among ME/CFS sufferers

I think yes, I rarely get normal people sick, at least flus or fever. I used to get at least once a year something that seemed like bronchitis, and had migraines for many years, though. Not sure which category they would fall into.

 

[Rufous McKinney]

I don't know the particular reason for you taking it, although it will help with cognitive issues, atleast temporarily. Starting with a low dose is a good idea.

a recent study found it helped improve the vagus nerve so it might actually help something improve rather than just being a "lift".

(and I am entirely forgetting now what all that was, from last week)

 

[Ali_Mardiyev]

a recent study found it helped improve the vagus nerve so it might actually help something improve rather than just being a "lift".

(and I am entirely forgetting now what all that was, from last week)

What's interesting in my particular case, I have absolutely no memory issues, possibly even improved memory. I believe it's due to high CRH signalling, which is know for supressing appetite, libido, rasing blood pressure, heart rate and improving memory. I have all of this symptoms

 

[Rufous McKinney]

I have absolutely no memory issues, possibly even improved memory.

I"ve been sick for decades, and memory issues only worsened recently.

 

[Rufous McKinney]

It also has certain anti-inflammatory effects
See this study: https://www.google.com/url?sa=t&sou...8QFnoECBcQAQ&usg=AOvVaw2SlLNdWmi16Xh5f3XWkVqH

that was new info, I need to sit down and better understand how it might help me and therefore maybe I can hang in there a bit trying to take it.

(I only lasted two days on SSRI's)

 

[Ali_Mardiyev]

that was new info, I need to sit down and better understand how it might help me and therefore maybe I can hang in there a bit trying to take it.

(I only lasted two days on SSRI's)

I'm against SSRI's. I took magnesium glycinate for 2 weeks, it's known to mildly raise serotonin levels, improve sleep and alleviate anxiety.
Did the exact opposite to me: worse sleep, extremely vivid dreams(hasn't subsided 7 days after stopping), anhedonia, lowered my libido.
I think our problem is low dopamine, rather than serotonin. Serotonin is probably high, due to excessive tryptophan accumulation

 

[hapl808]

I think our problem is low dopamine, rather than serotonin. Serotonin is probably high, due to excessive tryptophan accumulation

I broadly agree with this. I don't think the problem is necessarily just 'low dopamine', but inability to maintain appropriate dopamine homeostasis. Also, I wouldn't be surprised if it's more related to norepinephrine as there is a lot of overlap.

For me, anything that is 'stimulating' causes terrible crashes. That includes social stimulation, mental stimulation, sexual stimulation, etc. Pretty much anything that gives me the slightest 'adrenaline rush' feeling leads to an awful crash. In addition, one of my early symptoms I noticed after initial onset when I was still 'mild' for ME/CFS was a huge drop in any endorphins - after exercise in particular. My workouts went from 60 mins to maybe 15 mins before I'd get too exhausted, and that 'great feeling' after workouts disappeared entirely.

 

[Ali_Mardiyev]

I broadly agree with this. I don't think the problem is necessarily just 'low dopamine', but inability to maintain appropriate dopamine homeostasis. Also, I wouldn't be surprised if it's more related to norepinephrine as there is a lot of overlap.

For me, anything that is 'stimulating' causes terrible crashes. That includes social stimulation, mental stimulation, sexual stimulation, etc. Pretty much anything that gives me the slightest 'adrenaline rush' feeling leads to an awful crash. In addition, one of my early symptoms I noticed after initial onset when I was still 'mild' for ME/CFS was a huge drop in any endorphins - after exercise in particular. My workouts went from 60 mins to maybe 15 mins before I'd get too exhausted, and that 'great feeling' after workouts disappeared entirely.

I know that dopaminergic drugs supress glial cell activation, and lower glutamate, which is overactive in CFS/ME.
So possibly overactive glial cells disrupt dopamine "homeostasis."
I for sure have low dopamine receptor sensitivity.
I did 15 injections of dexamethasone in a span of 56 days, and during that time I was training 6 times a week, drinking 2-3 cups of coffee everyday and listening to a lot of music. All of this things contribute to dopamine release, plus high dose corticosteroids release dopamine as well(can link a study if interested). So I'm fucked in that sense.