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High (extracellular) serotonin causes Alzheimer's and depression

haidut

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The utter corruption of "journalism" is once again on full display in MSM. The actual scientific study is very clear in its statements/conclusions that a decrease in the levels of serotonin transporter (5-HTT) led to accumulation of beta-amyloid and onset of depression. Lower levels of 5-HTT - the protein that deactivates serotonin - means higher extracellular serotonin levels. The most popular class of "antidepressant" drugs - the SSRI - inhibit precisely the activity of 5-HTT and thus, according to the article findings, taking an SSRI may cause Alzheimer's disease (AD) and/or depression. Yet, the popular press article twists this 180 degrees and shamelessly reports that "low serotonin" is the cause of these conditions, when the study claims the exact opposite. Call me extreme, but I think level of journalistic malevolence should be punishable by jail as it has the potential to poison the minds (and ruin the health) of millions of people around the world.

Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares - Translational Psychiatry
Amyloid Beta and Serotonin May Be Keys to Predicting Who Develops Late-Life Depression

"...“What’s unique about PET scans is that they enable us to look at chemicals localized in the living brain in relation to Aβ proteins associated with memory loss,” says Gwenn Smith, Ph.D., Richman Professor of Alzheimer’s and Related Dementias in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. “This was fundamental for our work because we were able to test hypotheses from past research on mice with dementia for our imaging study in the human brain.”"

"...In a series of tests using radiotracers — short-acting radioactive molecules that “light up” in a PET scan — the researchers looked at both sets of participants for the amounts of Aβ and serotonin transporter (5-HTT), a protein that regulates the amount of serotonin in nerve cells. The data collected from the PET scans were then analyzed using a mathematical formula that identified a pattern showing how Aβ accumulation relates to 5-HTT. The pattern, Smith says, was significantly higher in the late-life depression group, indicating that a decrease in 5-HTT is linked to higher levels of Aβ in different areas of the brain — and in turn, to depression. The researchers also examined the relationship between the mathematically derived pattern and the severity of depression. For all study participants, the more that the decreased serotonin/increased Aβ pattern was seen, the greater were the depressive symptoms. Lower serotonin levels, say the researchers, were previously linked to depression. Therefore, selective serotonin reuptake inhibitors — antidepressants that increase the amount of the brain chemical to a more normal level — have been prescribed for treatment of major depressive disorders, anxiety disorders and other psychological conditions. “Our work reinforces the role of serotonin in late-life depression and the proteins associated with memory loss,” says Smith."
 

dilantinoid

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Joined
Mar 27, 2015
Messages
299
@haidut would buspirone (5h1 agonist) be helpful

Ray when asked specifically about busiprone responded “

“Blocking serotonin seems like a good idea.”
 

Jon2547

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Joined
Mar 2, 2021
Messages
629
What would this mean for Lysine? I think it affects the serotonin receptors in someway.
 

Drareg

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Feb 18, 2016
Messages
3,801
The utter corruption of "journalism" is once again on full display in MSM. The actual scientific study is very clear in its statements/conclusions that a decrease in the levels of serotonin transporter (5-HTT) led to accumulation of beta-amyloid and onset of depression. Lower levels of 5-HTT - the protein that deactivates serotonin - means higher extracellular serotonin levels. The most popular class of "antidepressant" drugs - the SSRI - inhibit precisely the activity of 5-HTT and thus, according to the article findings, taking an SSRI may cause Alzheimer's disease (AD) and/or depression. Yet, the popular press article twists this 180 degrees and shamelessly reports that "low serotonin" is the cause of these conditions, when the study claims the exact opposite. Call me extreme, but I think level of journalistic malevolence should be punishable by jail as it has the potential to poison the minds (and ruin the health) of millions of people around the world.

Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares - Translational Psychiatry
Amyloid Beta and Serotonin May Be Keys to Predicting Who Develops Late-Life Depression

"...“What’s unique about PET scans is that they enable us to look at chemicals localized in the living brain in relation to Aβ proteins associated with memory loss,” says Gwenn Smith, Ph.D., Richman Professor of Alzheimer’s and Related Dementias in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. “This was fundamental for our work because we were able to test hypotheses from past research on mice with dementia for our imaging study in the human brain.”"

"...In a series of tests using radiotracers — short-acting radioactive molecules that “light up” in a PET scan — the researchers looked at both sets of participants for the amounts of Aβ and serotonin transporter (5-HTT), a protein that regulates the amount of serotonin in nerve cells. The data collected from the PET scans were then analyzed using a mathematical formula that identified a pattern showing how Aβ accumulation relates to 5-HTT. The pattern, Smith says, was significantly higher in the late-life depression group, indicating that a decrease in 5-HTT is linked to higher levels of Aβ in different areas of the brain — and in turn, to depression. The researchers also examined the relationship between the mathematically derived pattern and the severity of depression. For all study participants, the more that the decreased serotonin/increased Aβ pattern was seen, the greater were the depressive symptoms. Lower serotonin levels, say the researchers, were previously linked to depression. Therefore, selective serotonin reuptake inhibitors — antidepressants that increase the amount of the brain chemical to a more normal level — have been prescribed for treatment of major depressive disorders, anxiety disorders and other psychological conditions. “Our work reinforces the role of serotonin in late-life depression and the proteins associated with memory loss,” says Smith."
Confirmation bias from the MSM, most of them are clearly downing SSRI’s everyday.
 

haidut

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Is 5-HTT the same as SERT?

Yes, different names for the same thing. Since "5-HT" is a commonly used abbreviation for "serotonin" in medical publications, "5-HT" + "T" is "serotonin transporter" also known as SERT (SER+T).
 

haidut

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@haidut would buspirone (5h1 agonist) be helpful

Ray when asked specifically about busiprone responded “

“Blocking serotonin seems like a good idea.”

I could help, though cyproheptadine and Benadryl are probably safer and more widely available.
 

Perry Staltic

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Dec 14, 2020
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I think SSRI inhibition of SERT would also increase serum serotonin because platelet storage of 5-HT would also be inhibited (same transporter). Since 5-HT is constantly being absorbed in the gut into the blood stream, but it's not being stored as much in platelets (because of SERT inhibition), it has to remain in serum until it is metabolized somewhere (e.g., lungs, liver).
 

Perry Staltic

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I'm wondering if SSRIs themselves are causing Alzheimer's. Fibrils are a characteristic feature of the disease, and SSRIs are 5HT-2B agonists, which promotes fibrosis.
 

Jon2547

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Doesn't Lysine play a role in serotonin blocking?
 
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I could help, though cyproheptadine and Benadryl are probably safer and more widely available.
I was just having a discussion about cypro causing depressed mood on another thread... why would it have that effect (even at low doses .5-1mg) if lowering serotonin should be helpful against the development of depression?
 

haidut

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I was just having a discussion about cypro causing depressed mood on another thread... why would it have that effect (even at low doses .5-1mg) if lowering serotonin should be helpful against the development of depression?

Both cypro and Benadryl cause strong sedation initially due to their histamine antagonism and that may be interpreted as a depression. However, in my experience at least, after a week of daily usage the sedation wears off and then both of them actually improve mood.
 
Joined
Dec 3, 2020
Messages
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Both cypro and Benadryl cause strong sedation initially due to their histamine antagonism and that may be interpreted as a depression. However, in my experience at least, after a week of daily usage the sedation wears off and then both of them actually improve mood.
Hm, I was definitely 'weepy' and emotional the day after and I think the other person (also female) reported the same effects. I didn't feel tired... but I also did not persist with consistent daily use (backed off to once per week) as the symptom was worrying me but sounds like she did.

Has anyone experienced depression - mood swing like symptoms - from taking Periactin? Have taken 1/4 - 1/2 tablet on & off as really helps me sleep & reduces ringing in my ears but Ive also started being super emotional! Wondering if its dropped my serotonin too low & what I can do to balance back up to normal? St Johns wort maybe?
 

aliml

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Melatonin inhibits serotonin transporter activity in intestinal epithelial cells

Gastrointestinal serotonin (5-HT) and melatonin are two closely related neuromodulators which are synthesised in the enterochromaffin cells of the intestinal epithelium and which have been shown to be involved in the physiopathology of the gastrointestinal tract. The effects of 5-HT depend on 5-HT availability which is, in part, modulated by the serotonin transporter (SERT). This transporter provides an efficient 5-HT uptake after release and is expressed in the membrane of the enterocytes. Although the origin and effects of 5-HT and melatonin are similar, the interrelationship between them in the gastrointestinal tract is unknown. The main aim of this study was to determine whether melatonin affects SERT activity and expression, and, if so, to elucidate the mechanisms involved. Caco-2 cell line was used to carry out the study as these cells have been shown to endogenously express SERT. The results showed that melatonin inhibits SERT activity by affecting both V(max) and kt kinetic constants although SERT synthesis or intracellular trafficking did not appear to be affected. The melatonin effect seemed to be independent of melatonin receptors MT(1) and MT(2) and protein kinase C and cAMP intracellular pathways. Our results suggest that the inhibition of SERT might be due to a catalytic effect of melatonin on the allosteric citalopram-sensitive site in SERT. This study shows, for the first time, that melatonin modulates SERT activity, thus demonstrating the feedback system between melatonin and the serotoninergic system in the gastrointestinal tract.

 

J.R.K

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I am curious on your thoughts @haidut. You have mentioned that crabs become cannibalistic when SSRI’s are introduced into their environment through treated wastewater.
But if a person was in an intimate relationship with someone on SSRI’s, would they be putting their health in danger as well by transmission of fluids internalizes or absorption through transdermal contact with fluids or shedding if you will allow the crossover term from the viral world.
To me it seems like a credible possibility but I am wondering if there was any data available that you have come across, that would support or discredit this hypothesis?
 

username

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Nov 17, 2020
Messages
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Both cypro and Benadryl cause strong sedation initially due to their histamine antagonism and that may be interpreted as a depression. However, in my experience at least, after a week of daily usage the sedation wears off and then both of them actually improve mood.
What dosage do you recommend with cypro and Benadryl?
 

lampofred

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Feb 13, 2016
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The study definitely uses tricky wording, but it doesn't seem very safe to me to chronically lower serotonin via pharmaceuticals to combat Alzheimer's/depression. The serotonin transporter goes down due to insufficient levels of salt in the diet, so I think eating more salt is the best way to keep serotonin low, rather than using pharmaceuticals, because in addition to lowering serotonin, salt also lowers histamine (because it raises CO2 production). The problem with pharmaceuticals is that by lowering serotonin without necessarily raising CO2 production, they might have the side effect of raising histamine.

I think serotonin might go up as a protective reaction against excess histamine, as dulling the emotions via serotonin is the body's back-up way of protecting against the emotional instability caused by histamine when the body doesn't have enough energy to produce CO2, which is the healthy way to keep histamine low.

It seems the real cause of Alzheimer's and depression might be excess histamine, not excess serotonin. But lowering histamine is hard, aside from milk, thyroid, vitamin D, coffee, chocolate, niacinamide, salt, and cold showers, I don't really know what else works.
 

J.R.K

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Aug 4, 2020
Messages
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The study definitely uses tricky wording, but it doesn't seem very safe to me to chronically lower serotonin via pharmaceuticals to combat Alzheimer's/depression. The serotonin transporter goes down due to insufficient levels of salt in the diet, so I think eating more salt is the best way to keep serotonin low, rather than using pharmaceuticals, because in addition to lowering serotonin, salt also lowers histamine (because it raises CO2 production). The problem with pharmaceuticals is that by lowering serotonin without necessarily raising CO2 production, they might have the side effect of raising histamine.

I think serotonin might go up as a protective reaction against excess histamine, as dulling the emotions via serotonin is the body's back-up way of protecting against the emotional instability caused by histamine when the body doesn't have enough energy to produce CO2, which is the healthy way to keep histamine low.

It seems the real cause of Alzheimer's and depression might be excess histamine, not excess serotonin. But lowering histamine is hard, aside from milk, thyroid, vitamin D, coffee, chocolate, niacinamide, salt, and cold showers, I don't really know what else works.
That is some great information @lampofred. Thank you for expanding my knowledge.
I was not aware that salt is a serotonin antagonist. When I think of serotonin antagonists myself I think of collagen, carrot salad, mushrooms, and bamboo shoots, all trying to keep the LPS down and the gut clean as possible.
I knew about salts antagonist effects on aldosterone, and thinking about it I am wondering about the daisy chain effect that might be related to upregulation of one stress hormone leading to upregulation of another, perhaps there is a connection.
The melatonin I remain unsure of for now, the ability to sleep soundly is not an issue. But I am unsure still about melatonin and serotonins relationship. So like the gene therapies I will steer clear for now.
 

TeslaFan

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Joined
Jul 25, 2013
Messages
266
The study definitely uses tricky wording, but it doesn't seem very safe to me to chronically lower serotonin via pharmaceuticals to combat Alzheimer's/depression. The serotonin transporter goes down due to insufficient levels of salt in the diet, so I think eating more salt is the best way to keep serotonin low, rather than using pharmaceuticals, because in addition to lowering serotonin, salt also lowers histamine (because it raises CO2 production). The problem with pharmaceuticals is that by lowering serotonin without necessarily raising CO2 production, they might have the side effect of raising histamine.

I think serotonin might go up as a protective reaction against excess histamine, as dulling the emotions via serotonin is the body's back-up way of protecting against the emotional instability caused by histamine when the body doesn't have enough energy to produce CO2, which is the healthy way to keep histamine low.

It seems the real cause of Alzheimer's and depression might be excess histamine, not excess serotonin. But lowering histamine is hard, aside from milk, thyroid, vitamin D, coffee, chocolate, niacinamide, salt, and cold showers, I don't really know what else works.

Riboflavin, Magnesium, B6, Folates to keep histamine in check. Works for me.
 
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