cdraham wrote: ↑Sat Sep 04, 2021 5:01 pm
guacamo wrote: ↑Sat Sep 04, 2021 3:58 pm
I edited the main post, u can check this up.
Thanks, I read your theory. I have a question..
How does this explain the chronic fatigue, loss of muscle, head pressure and other symptoms seen in severe pssd?
You forget that serotonin is a potent Immune Cell Modulator (
https://www.frontiersin.org/articles/10 ... 00186/full). A downregulation of the presynaptic autoreceptor would lead to an increased binding of serotonin to all 5HT receptors. The consequences in predisposed individuals (those with defective immune genes) could be unexpected. 5HT results in Th1/Th17 shift, so this theory could easily explain all of the symptoms you mentioned, including CD57+ dysfunction, although molecular mechanisms are still unknown.
Moreover, elevated serotonin would directly alter other neurotransmitters through G-coupled proteins and heterodimers as well as sodium/potassium/calcium homeostasis. Let me provide you a few examples. 5HT2A has a connection with mGlur, Cb1, D2. 5HT2C directly inhibits dopamine and norepinephrine. 5HT3 is a ligand-gated ion channel similarly to GABA or NMDA, which pushes sodium into a cell. It is also worth mentioning that 5HT3 is one of those recetors that do not work in negative feedback manner (it is upregulated from both agonism and antagonism), and they are tend to recover for a longer period of time (Benzo-withdrawal etc.).
I'd also like to say that my Th2 cytokines are undetectable on my blood tests, while my Th1 cytokines are still in the perfect middle of the range. Moreover, my tryptophan and serotonin are also elevated. And yes, I had a great window with dexamethasone. I still believe that while serotonin is a cause of some symptoms, other symptoms like anhedonia, inflammation, cognitive dysfunction, fatigue are mostly caused by immune dysfunction induced by serotonin in predisposed individuals.
Murine basophils were found to participate in the Th2 polarization by instantly secreting lots of IL-4, whereas 5-HT could downregulate this IL-4 production by basophils in vitro and in vivo
.
I would like to say thanks to guacamo for his work. For me it is still not clear how SSRIs do result in permanent changes in 5HT1A autoreceptor, but I must admit that collected data on cured cases, and provided studies were indeed extremely intriguing. I am also curious what you are trialing regarding your theory as I have researched all compounds that interfere with serotonin.