41 replies to this topic

[StevesPetRat]

Well, obviously not in *every* case. Sadly, the vocabulary and diagnostic repertoire of psychiatry are still embarrassingly primitive, so we can only really speak of "depressed mood" and "treatment resistant depression". However, there is solid research suggesting in some circumstances it involves serious immune malfunction. As far as I could find, no previous thread has mentioned these studies so here they are.
First, the Th17 branch of the immune system is overactive in depressed patients
http://www.ncbi.nlm....ubmed/21129782/
(Oh here is the rat model, of course, http://www.ncbi.nlm....ubmed/23174342/ )

This paper identifies anti-phosphatidyl inositol antibodies as being active in MDD (and ME/CFS)
http://europepmc.org...ct/med/18063934
Perhaps this is why inositol supplements help with depression -- they either induce tolerance or simply give the antibodies something else to latch onto, leaving the rest of the body's inositol alone so it can do whatever cell signalling stuff it needs to do.

Now, what is "Th17"? As I understand it, it is a subset of T helper cells devoted primarily to mucous membrane defense, i.e. the gut! It was only discovered recently, but already there are studies implicating it in nearly every autoimmune disease. I won't link all the studies here, but you can easily google Th17 + psoriasis, rheumatoid arthritis, lupus, Sjogren's syndrome, anti phospholipid syndrome, Crohn's disease, vasculitis, type 1 diabetes, etc etc etc. I don't know about the rest of you, but my longtime depression was triggered by EBV, already implicated in other autoimmune diseases, and it certainly has the "flare and remission" pattern characteristic of such diseases.

I can't find it now, of course, but I swear I've read that depression increases the risk of autoimmune disease by something like a factor of 2. I did find this link between schizophrenia and autoimmunity:
http://www.ncbi.nlm....ubmed/16513876/
Researchers have been looking at schizophrenia as a possible autoimmune disorder for at least a decade
http://www.nature.co.../icb20052a.html
Yet the question has barely been raised for depression!

So, you're depressed. The shrink has been moving you from SSRI to SNRI to another SSRI with little to show for it, and you can't get your hands on some NSI-189. You don't exactly feel sad. You feel ill all the time. What will turn down the Th17 system?
Well, the usual stuff - sorry for no links, writing on phone, it's a pain. (Thanks to Hip for some of these!)
Exercise
Fixing sleep cycle
Lowering gut inflammation
Reducing stress
Proline restriction
Intermittent fasting

And the supplemental stuff
Circumin
Retinoic acid
Vitamin D3
Zinc
Ursolic acid (spray is more bioavailable)
Low dose naltrexone (maybe dexreonaltrexone, which could be used in a much higher dose as it doesn't mess with the opioid receptors, only the TLR4 receptors -- OK toll like receptor 4 and lipopolysaccharides aka LPS probably deserve their own thread)
ECGC
Resveratrol
Berberine
DHA
Cannabidiol
N-acetylglucosamine
Propolis
Baicalin
Grape seed extract
Triptolide
Cordyceps
Fucoxanthin
Olive leaf
Luteolin

And that's all I got. Thoughts?

[medievil]

Brain inflammation is not that hard to fix according to my research, arb blockers amelirate brain inflammation.

 

 

Angiotensin II AT1 receptor blockade ameliorates brain inflammation.

Benicky J¹, Sánchez-Lemus E, Honda M, Pang T, Orecna M, Wang J, Leng Y, Chuang DM, Saavedra JM.

Author information

• ¹Section on Pharmacology, Division of Intramural Research Programs, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. benickyj@mail.nih.gov

Abstract

Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT(1) receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders.

 

 

[StevesPetRat]

Hmm found another study on it. Interesting stuff, I would try it.
http://d-scholarship.pitt.edu/8497/
I suppose it's one of those drugs you can get your hands on?
Also, what if you don't have high blood pressure? Orthostatic hypotension?

[medievil]

Yup,

 

I take it with verapamil and propranolol allways had normal blood pressure and its still fine.

[medicineman]

I take telmisartan 20mg od (for its anti-inflammatory and ppar-gamma activity) and carvedilol 3.5mg bd. I suggest, if you are not taking propranolol for a medical reason, to check out carvedilol. it is the most superior adrenergic blocker, in terms of cardioprotection and anti-inflammation. here is a little sample

"The antioxidant properties of carvedilol result from the carbazole moiety in its structure (Figure). Carvedilol is a potent antioxidant, 10 fold more potent than vitamin E.[10] Its metabolites are 30-80 times more potent than carvedilol and up to 1000-fold more potent than vitamin E."

After hard and vigorous discussion with the cardiology staff in my center, carvedilol has become THE adrenergic blocker of use unless obviously not indicated.

There's a lot of amazing research done on it, and it supercedes all adrenergic blockers by a long shot. Not only has it proven itself clinically, but I feel that it may have a place, like low dose aspirin, as a preventative drug.

Just to wet your appetite some more, check out the observational research showing that carvedilol reduces risk of dementia, and there's also a study going on specifically for dementia and carvedilol as intervention.

Edited by medicineman, 17 July 2014 - 03:35 PM.

[StevesPetRat]

Ha, good stuff. Combine it with dihexa and its slight increase in blood pressure effects.

I thought I would add this blood test for Th17 levels. Not prohibitively expensive. Hope to try it soon.
http://www.truehealt...t.aspx?id=38430

[Nemo888]

TB4 an HGH worked incredibly well in my case. One unit of each per day.  After using them my vitamins and supplements sit unused. By comparison they are useless.

[Max Headroom Incident]

I suspect many "mental health" disorders are immune-related.  We already know PANDAS (OCD caused by strep infection) is a thing, so why couldn't depression/autism/others be autoimmune too?  I have multiple forms of anxiety and depression and consistently high lymphocyte counts when my blood is drawn.  I even had one doctor ask if I "felt okay" because my white blood cells were so high...I wasn't sick at all.   

 

The book "Infectious Behavior: Brain-Immune Connections in Autism, Schizophrenia and Depression" explores this subject in great depth.  It made a believer out of me.  I imagine there are almost infinite causes of mental illness, but out-of-control immune function is most certainly among them. 

Edited by Max Headroom Incident, 19 July 2014 - 02:15 PM.

[HailtoB]

"I can't find it now, of course, but I swear I've read that depression increases the risk of autoimmune disease by something like a factor of 2. I did find this link between schizophrenia and autoimmunity:
http://www.ncbi.nlm....ubmed/16513876/"

 

I have Hashimoto's disease, and when I had a blood test returned around the same time, my vitamin D levels were extremely low. Aka, depression and autoimmune diseases go hand in hand.

[noos]

I take telmisartan 20mg od (for its anti-inflammatory and ppar-gamma activity) and carvedilol 3.5mg bd. I suggest, if you are not taking propranolol for a medical reason, to check out carvedilol. it is the most superior adrenergic blocker, in terms of cardioprotection and anti-inflammation.

 

 

Does carvedilol cross the BBB? Any anti-anxiety effects like with propranolol?. Thanks.

[Nemo888]

I think the king for neural/neuronal inflammation and neurorestoration is thymosin beta 4. Cheap and safe to try if you are comfortable with injections. 30 days at 1mg a day seemed ideal for me.

[Duchykins]

I'm thinking that any chronic problem can cause depression and that depression can cause a variety of chronic medical problems. Especially gut problems because of the strong brain-gut connection, and compromised sleep which affects every last cell in your body. "Treatment-resistant" depression isn't a terribly useful term in the practice, even in the literature, because of all the strong emphasis on serotonin supporting drugs, lack of variety of non-agonist dopamine, norepinephrine and GABA supporting drugs, and of course nutritional corrections or any serious effort correct sleep abnormalities or find even the cause of the depression. So many docs don't bother ordering nutrient profile tests, it doesn't even occur to most.

[noos]

candesartan or carvedilol?

[medicineman]

I take telmisartan 20mg od (for its anti-inflammatory and ppar-gamma activity) and carvedilol 3.5mg bd. I suggest, if you are not taking propranolol for a medical reason, to check out carvedilol. it is the most superior adrenergic blocker, in terms of cardioprotection and anti-inflammation.

 
 
Does carvedilol cross the BBB? Any anti-anxiety effects like with propranolol?. Thanks.

it is a lipophilic beta blocker so it should, but it's not as CNS active (based on subjective trials) as propranolol.

[StevesPetRat]

I've found a bit more about the involvement (more specifically, deficiency) of IL-10 -- generally regarded as anti-inflammatory, though of course in reality it's more complicated -- in depression.

http://www.hindawi.c...pn/2009/187894/

Here are a few very tentative ways to raise IL-10

Probiotics (B. breve) http://www.plospatho...al.ppat.1002714

Garlic(very tentative) http://www.journals....002723/abstract

Exercise http://arthritis-res...ntent/12/4/r126

Glycine http://www.fasebj.or...t/13/3/563.full

* note that although gelatin is a great source of glycine, it is also high in proline, which may be counterproductive.

 

Oh, and what's that? IL-10 deficiency makes mouse multiple sclerosis worse? (OK, OK, it's called EAE)

http://www.jimmunol....161/7/3299.long

And this article makes the picture terrible complicated. Too much IL-10 also seems bad, although it may be a consequence of over-reactivity rather than a causative factor

http://pharmrev.aspe...t/55/2/241.long

 

 

[StevesPetRat]

Belated update on a possible connection between depression and (a decrease in) long term potentiation. Anti-phosphatidylinositol antibodies block LTP.

[normalizing]

very good thread. its so old though, im surprised there wasnt more contributed to it in all those years, BUT i really find it a good thread and i hope people do contribute more from now on and im going to follow on it

[StevesPetRat]

Microbiome is important (of course)

SCFA's (butyrate in particular as well as propionate) and acetate. (Many other references can be found by searching th17 + those acids)

[normalizing]

ive been using short chain fatty acid like sodium butyrate but nothing different. it smells like vomit though, that is its drawback

[StevesPetRat]

ive been using short chain fatty acid like sodium butyrate but nothing different. it smells like vomit though, that is its drawback

 

I've found tributyrin to be more effective. Also I have been taking about 5 grams at a time (given that it is a product of fiber fermentation, this is not toooooo excessive).

 

Can't help you with the smell, though...

[normalizing]

in what way did you find tributyrin more effective??

[CalmAmygdala]

TB-500 reduces neuro-inflammation? Is it as good as ibudilast or galantamine?

[normalizing]

tb500 ?

[StevesPetRat]

in what way did you find tributyrin more effective??

 

In a highly subjective way. I notice occasionally that I get what feels like a burst of clear thinking or recall of old memories after taking cal/mag or na/k butyrate, but this effect is transient (1 hr or less). On the other hand, on tributyrin, it seems like this effect, when it occurs, lasts much longer.

 

TB-500 reduces neuro-inflammation? Is it as good as ibudilast or galantamine?

 

It has a very different mechanism of action than ibudilast, as far as I can tell. However, it should potentiate the effects of Dihexa, as it increases the release of HGF. Dihexa in turn increases the binding of HGF to its receptors.

[normalizing]

i found info on this supplement; https://www.amazon.c...ords=tributyrin wow thats so expensive. are you buyng something like this?but why, so expensive...

[John250]

i found info on this supplement; https://www.amazon.c...ords=tributyrin wow thats so expensive. are you buyng something like this?but why, so expensive...

From what I’ve read it’s the best for improving tyrosine hydroxylase. I ordered it along with free acid butyrate to take when I get off amphetamines. I probably spent close to $1000 a month on supplements and this one was probably the most expensive come to think of it.

The real question is what is the proper therapeutic dose? When a supplement is this expensive and it says take 1-3 per day knowing that factor is pretty important.

Edited by John250, 13 July 2018 - 04:20 PM.

[normalizing]

butter is high source of tributyrin. why not just consume butter? bulletproof coffee is almost like an amphetamine

[John250]

butter is high source of tributyrin. why not just consume butter? bulletproof coffee is almost like an amphetamine

It would take a ton to get the amount. Butter only has trace amounts

https://biofoundatio...-form-butyrate/

[normalizing]

i see. i still dont understand why tributyrin is rare and so expensive...

[John250]

i see. i still dont understand why tributyrin is rare and so expensive...

Me neither but I just bought 2 bottles to take the max dose during my amphetamine withdrawl as it seems to be very beneficial. More info here.

https://mybiohack.co...amine-naturally