Author Topic: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?  (Read 5198 times)

superfrancais

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Dear colleagues of misfortune, I know we have no symptoms of schizophrenia but most of us experience some kind of brain inflammation during our POIS periods, with severe brain dysfunction.

I found the following articles today (the French one in the most popular French news site) saying that some cases of schizophrenia could be caused by the body attacking itself and blocking NMDA receptors. The interesting thing is that it would make schizophrenia scientifically diagnosable (not just by symptoms), just by searching for the presence of specific antibodies.

I don't want to bring any false hope of diagnosis of our disease, but I really think it would be interesting to seek these very antibodies in POIS sufferers. I have a strong intuition that we would find them.

What do you think? Am I hallucinating :-)
 
English team (article in English):
http://www.healthline.com/health-news/mental-could-schizophrenia-be-caused-by-autoimmune-disease-022014#1

French team (article in French):
http://sante.lefigaro.fr/actualite/2015/12/07/24384-schizophrenie-piste-auto-immune
20 years of both mental and physical symptoms after love, chronic fatigue and depression even with abstinence, French (Lyon)

Macster

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #1 on: December 09, 2015, 08:36:43 AM »
Very interesting superfrancais, this would be particularly interesting to test in the case of POIS: "Clean the Blood, Protect the Brain
To test this theory?and to help their patient?the team treated one man with plasmapheresis, a procedure that filters antibodies out of the blood". I do believe myself that mental illnesses may have some root in autoimmune disorders.
Symptoms since I'm 15 y o, hair loss, muscle twitches, brain fog, anxiety, low confidence, stuffy nose, itchy eyes and skin, sensitive to temperature change, loud heartbeat. I currently use 5-htp and SAM-e.

Quantum

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #2 on: December 09, 2015, 09:28:38 PM »
Bonjour Superfrancais, et Macster,

I do agree the the encephalitis ( brain inflammation) related symptoms of POIS seems to be related to an immune over-reaction.

I talked about that earlier this year, in particular here: http://poiscenter.com/forums/index.php?topic=1988.msg15559#msg15559  .  You may be interested to the slide show I am linking to in this message ( http://fr.slideshare.net/adonissfera/tryptophan-and-madness ), in particular the slide #17, http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory ).  You can see there that the excitotoxic substance I refer too ( quinolinic acid and kynurenic acid) act through the NMDA receptors, and cause brain inflammation and brain cells death, manifesting as cognitive symptoms ( for kynurenic acid toxicity) and emotional symptoms ( for quinolinic acid toxicity).  I have found that very interesting, because I have a lot of emotional symptoms, but no cognitive symptoms, and the fact that 2 different pathways could lead to one or the other "cluster" of symptoms would explain why I was not having those cognitive symptoms the majority of POIS sufferers have, while having the emotional ones ( Meaning I should be more sensitive to quinolinic acid toxicity, and not to kynurenic acid toxicity).  These hypothesis are still part of my current overall "theory" about POIS cause.

When I read about that neurotoxicity/excitotoxicity thing, I have started to use even more NMDA receptors blockers in my anti-POIS pre-E pack.  In fact, I was already using magnesium for years, which is a a good NMDA receptor blocker, but didn't know it could be the reason why it was helping reduce my POIS symptoms  ( anybody else have tried magnesium for POIS relief ?).  NMDA receptors blockers act as neuroprotectors against the excitotoxins, so they prevent brain inflammation.  Apart from magnesium, the other NMDA receptors blockers I have found useful for me are flaxseed oil ( the lignam in it is the NMDAR blocker), L-theanine, taurine, and ibuprofen.  I didn't try yet cat's claw and huperzine A.  I have tried acetyl-L-carnitine, but not sure if it helps me or not.

In my pre-pack, I use magnesium, lignam ( flaxseed oil) and L-theanine).  They work for me, even though I do not know for sure it is for the exact reason I am talking about in this message ( brain excitotoxicity of quinolinic acid and kynuretic acid produced through the tryptophan pathways "hacking" by an immune over-reaction ).

One note, however: the excitotoxicity effect through NMDA receptors do not necessarily implies the presence of NMDAR antibodies, it can be triggered through the innate immune system too ( https://en.wikipedia.org/wiki/Innate_immune_system ), by the production of inflammatory cytokines ( antibodies are produced by the lymphocytes cells of that adaptive branch of the immune system). So, NMDA receptors antibodies are not the only way that NMDA receptors can be affected  ( brain inflammation can occur through an effect on NMDAR, without any NMDAR antibodies that can be found and use as a diagnostic criteria).




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Stef

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #3 on: December 09, 2015, 09:29:43 PM »
Hi, superfrancais,

There's been a lot of research on the anti-NMDAR auto-antibody. It can cause a type of encephalitis that presents as a psychosis -- hallucinations, catatonia, weird postures, paranoia, and in some women  -- anorexia nervosa. Patients have ended up on psych units, inappropriately and unsuccessfully treated for years.

There was a major article written back around 2011, by a young New York Post reporter, Susannah Cahalan. She went from normal to psychotic almost overnight, and was admitted to a NY hospital psychiatric unit. Her case was documented with videos, in addition to medical records. Many psych meds were given without success -- for a full month.

Her parents wouldn't give up, and eventually, after a month on the psych unit, they learned about Dr. Souhel Najjar, a neurologist with a specialty in immunology, from NYU.  Dr. Najjar consulted, did the right tests, and diagnosed her with anti-NMDAR encephalitis, an autoimmune condition. She was treated successfully with plasmaphooresis and steroids.

She then wrote a book about the experience, Brain on Fire. Her book brought a lot of attention to this frequently misdiagnosed condition. http://www.susannahcahalan.com

As I understand it, this abnormal antibody doesn't cause schizophrenia. Rather, some patients with schizophrenia symptoms have been found to have the anti-NMDAR antibody...so what they really have is a form of encephalitis.

Honestly, I think it would be a stretch to connect POIS to this abnormal antibody, because the symptoms are so sudden and severe. Also, I haven't read that they're exacerbated by ejaculation.

But, superfrancais -- you've brought up a very important subject! Many physical illnesses present with psychiatric symptoms...and remain undiagnosed for years.

Stef
« Last Edit: December 09, 2015, 09:38:36 PM by Stef »

demografx

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #4 on: December 10, 2015, 01:46:46 AM »

It was a relief, years back Stef, when you advised that POIS was not unique in its challenges, especially the battle we face with doctors who falsely insist, "POIS is all in your head -- go see a shrink!"


10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

b_jim

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #5 on: December 10, 2015, 03:38:28 AM »
I'm not really a defender of immonologic theories about Pois but maybe I'm wrong.
Superfrancais's article is interresting but I really don't see the immune system as THE STARTING POINT of Pois.

The last post of Quantum makes me think of something : all the substances with a "calming effect" seems to help Pois.
Taurine = Anti-Pois
Suffering from lyme disease

G-man

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #6 on: December 11, 2015, 09:28:09 AM »
Quantum, is there any way to test for elevated quinolinic acid or kynurenic acid in the blood?
31 years old. POIS since puberty. Cognitive and physical symptoms.

superfrancais

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #7 on: December 11, 2015, 11:00:37 AM »
Thank you everybody for sharing your opinion on this topic. In the present post I'd like to comment on the following part of Quantum's reply.

When I read about that neurotoxicity/excitotoxicity thing, I have started to use even more NMDA receptors blockers in my anti-POIS pre-E pack.  In fact, I was already using magnesium for years, which is a a good NMDA receptor blocker, but didn't know it could be the reason why it was helping reduce my POIS symptoms  ( anybody else have tried magnesium for POIS relief ?).  NMDA receptors blockers act as neuroprotectors against the excitotoxins, so they prevent brain inflammation.  Apart from magnesium, the other NMDA receptors blockers I have found useful for me are flaxseed oil ( the lignam in it is the NMDAR blocker), L-theanine, taurine, and ibuprofen.  I didn't try yet cat's claw and huperzine A.  I have tried acetyl-L-carnitine, but not sure if it helps me or not.

My remark is simple. In the articles I linked in my initial post, the physicians (both in the English team and in the French team) explain that the problem comes from auto-antibodies wrongly blocking NMDA receptors. But when describing your vision and your cure you're saying the exact contrary, i.e. you take substances that are going to block NMDA receptors.

So, to block or not to block, that is the question :-)
20 years of both mental and physical symptoms after love, chronic fatigue and depression even with abstinence, French (Lyon)

Quantum

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #8 on: December 11, 2015, 12:53:08 PM »
Quantum, is there any way to test for elevated quinolinic acid or kynurenic acid in the blood?

Hi G-man,

I do not have much knowledge about biomedical lab techniques.  There is for sure known ways to do it, since there are plenty of studies using quinolinic acid or kynurenic acid levels measurements in their protocol ( for example, this article is a review of numerous studies about quinolinic acid effects on the brain : http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2012.08485.x/abstract;jsessionid=87DC6F5C5332B93D3DF0B8D17D1F704D.f01t04  ).

A quick search on the internet lead me to this link: http://www.sciencedirect.com/science/article/pii/000326977290440X .  it proves that there is more than one biochemical test available.  But I do not know if they are available on a large scale, or only in very specialized labs. 

It would be great to be able to be tested during POIS acute phase, but not sure if possible, and, how it would cost.  Some rare techniques are very expensive to use.
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Quantum

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #9 on: December 11, 2015, 01:59:54 PM »
Thank you everybody for sharing your opinion on this topic. In the present post I'd like to comment on the following part of Quantum's reply.

When I read about that neurotoxicity/excitotoxicity thing, I have started to use even more NMDA receptors blockers in my anti-POIS pre-E pack.  In fact, I was already using magnesium for years, which is a a good NMDA receptor blocker, but didn't know it could be the reason why it was helping reduce my POIS symptoms  ( anybody else have tried magnesium for POIS relief ?).  NMDA receptors blockers act as neuroprotectors against the excitotoxins, so they prevent brain inflammation.  Apart from magnesium, the other NMDA receptors blockers I have found useful for me are flaxseed oil ( the lignam in it is the NMDAR blocker), L-theanine, taurine, and ibuprofen.  I didn't try yet cat's claw and huperzine A.  I have tried acetyl-L-carnitine, but not sure if it helps me or not.

My remark is simple. In the articles I linked in my initial post, the physicians (both in the English team and in the French team) explain that the problem comes from auto-antibodies wrongly blocking NMDA receptors. But when describing your vision and your cure you're saying the exact contrary, i.e. you take substances that are going to block NMDA receptors.

So, to block or not to block, that is the question :-)

Your remark is very interesting, superfrancais.  I think the confusion came because of the words used by the journalists who were referring to the studies, without mastering the subject.  Words and expressions like "immobilizing the NMDA receptors" in the French account, and the phrase "When the immune system attacks the NMDA receptor, it becomes inflamed", are not accurate, because those journalist are not specialists.  For example, you can talk about inflammation for a tissue or an organ, but not for a single receptor, which is a the protein/molecule level, so the English phrase in not correct. 

That being said, I went back to read the original article, in order to hear it "straight from the horse's mouth" and understand what has been really been found by this research team, I have found the article at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065649/ .  I think the relevant part is the following: " These preliminary data show that some patients with schizophrenia have potentially pathogenic autoantibodies to relevant membrane proteins. "  , the relevant membrane proteins being parts of the NMDA receptors structures.  So, it says that the antibodies are "pathogenic" to the receptors, meaning they cause some sort of dysfunctions leading to schizophrenia symptoms, according to their hypothesis.  But there is no more precision on the nature of this pathogenic effect, apart form the fact that they know they binds to the NMDA receptors.  Do they block them in "on" position, or in "off" position?  Do they have another effect?  I think they do not have these answers yet.


What is well known form other sources is the excitotoxicity effect ( https://en.wikipedia.org/wiki/Excitotoxicity ), where an excessive stimulation NMDA receptors leads to nerve cell death, and, on a brain tissue level, to inflammation.  Quinolinic acid, a potent NMDA receptor agonist ( it stimulates it), is known to being able to cause excitotoxicity ( see at https://en.wikipedia.org/wiki/Quinolinic_acid ).  This bad effect occurs in the microglia, which is the first line immune defence cells of the brain tissue.  Quinolinic acid is known to cause emotional symptoms.

On the other end, kynurenic acid is a potent NMDA antagonist ( it blocks the NMDA receptors). It can leads to too much blocking , but on another type of brain support cells, the astrocytes. In this case, it is known taht high levels of kynurenic acids leads to cognitive deficit, confusion and psychotic symptoms ( https://en.wikipedia.org/wiki/Kynurenic_acid#Role_in_disease )

So, too much is no better than not enough.  You can have toxic effects both ways, on different type of brain cells.

You can see a good graphic synthesis of this on the image at http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory .  In bottom center of the slide, you will see that the a higher kynurenines ( KYN ) production can than lead to a raise concentration of quinolinic acid (QUIN), leading to a + effect on the NMDA receptors of the microglia cells, which manifests in depression, anxiety and impulsivity, as noted on the slide.  You can also see that the kynurenines ( KYN) can also be transformed in kynurenic acid ( KYNA on the slide), and this raise in KYNA concentration affects the astrocytes, having a - effect on the NMDA receptors, and lead to cognitive deficits ( yes, brain fog, memory problems, mental focus problems, .....). 


Moreover, the concept of "blocking" a receptor is not always a on-off reality - it is often a modulation of the receptor activity.  If you are really interested on all those interactions at the NMDA receptors, take a look at https://en.wikipedia.org/wiki/NMDA_receptor , and you will see it is more complicated that it appears.

So, not having all the information, sometime all is left is our personal response to a particular supplement, to see if it helps or not ( through trials with safe doses, of course).  In my case, the fact that I had no cognitive symptoms, it was clear that it was better for me to try NMDA blockers  ( which, anyway, are good for anxiety, something I have been living with since childhood).  Having just myself as "guinea pig", I don't know for sure if a POIS sufferer with both cognitive symptoms and emotional symptoms, would have less emotional symptoms and more cognitive symptoms if using NMDA blockers, but it do not seems to be the case.  From what have been share on the forum so far, I do not recall any member noticing worse cognitive symptoms after using flaxseed oil, l-theanine, magnesium, taurine, or another NMDAR blocker.

For me, at the least, my answer to your question, "to block or not to block" the NMDAR, is to block, and use NMDAR blockers.   Moreover, when I used to eat food containing aspartame, which ends in the brain as glutamate ( a NMDA agonist/stimulator), I would always have a typical dull and constant headache, sign of a certain level of neurotoxicity ( actually, aspartame is known to be a migraine trigger for many people).

I hope my answer is not too long and is clear enough, but there was no simple answer to this question :-)

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superfrancais

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #10 on: December 11, 2015, 02:46:34 PM »
I hope my answer is not too long and is clear enough, but there was no simple answer to this question :-)

Thank you for your quick and detailed answer, Quantum.

Your remark is very interesting, superfrancais.  I think the confusion came because of the words used by the journalists who were referring to the studies, without mastering the subject.  Words and expressions like "immobilizing the NMDA receptors" in the French account, and the phrase "When the immune system attacks the NMDA receptor, it becomes inflamed", are not accurate, because those journalist are not specialists.  For example, you can talk about inflammation for a tissue or an organ, but not for a single receptor, which is a the protein/molecule level, so the English phrase in not correct.

I think it's better to focus on the results of the French team since the results are more recent and they just won an award. I could not yet get the scientific paper in question, but in order to understand better I found another vulgarization paper (link below, in French). It seems the phrase "immobilizing the NMDA receptors" has to be taken literally. They have observed, on rats, that these NMDA receptors are moving at the surface of the synapse in healthy rats. And that these receptors are immobilized in rats exposed to a certain kind of auto-antibodies known to cause autoimmune brain inflammation. The capacity of movement is said to be required for the brain plasticity (i.e. its capacity to adapt itself).

http://www.c-yourmag.net/post/2014-08-06/troubles-psychotiques-une-piste-pour-les-comprendre
20 years of both mental and physical symptoms after love, chronic fatigue and depression even with abstinence, French (Lyon)

Stef

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #11 on: December 11, 2015, 05:01:07 PM »
Re: the subject of auto-antibodies and autoimmune disorders --

I think it's important to keep in mind that auto-antibodies are never normal and are always destructive. That's the basis of autoimmune disorders.

It's one thing to take a supplement that blocks the NMDA receptors (eg. magnesium), and to take it for a given time to decrease certain symptoms.

But an anti-NMDA receptor auto-antibody -- aka "anti-NMDAR" auto-antibody -- is generated for unknown reasons by the person's own immune system. It attacks the NMDA receptors and disrupts the production of their protein. These receptors are predominately located in brain tissue, which is why the manifestations are mainly psychological and can be so severe (schizophrenia/psychosis symptoms).

POIS may have an autoimmune component -- but no one knows yet.

Stef





Quantum

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #12 on: December 11, 2015, 10:48:02 PM »
Re: the subject of auto-antibodies and autoimmune disorders --

I think it's important to keep in mind that auto-antibodies are never normal and are always destructive. That's the basis of autoimmune disorders.

It's one thing to take a supplement that blocks the NMDA receptors (eg. magnesium), and to take it for a given time to decrease certain symptoms.

But an anti-NMDA receptor auto-antibody -- aka "anti-NMDAR" auto-antibody -- is generated for unknown reasons by the person's own immune system. It attacks the NMDA receptors and disrupts the production of their protein. These receptors are predominately located in brain tissue, which is why the manifestations are mainly psychological and can be so severe (schizophrenia/psychosis symptoms).

POIS may have an autoimmune component -- but no one knows yet.

Stef

Hi Stef,

Thanks for taking the time to point this out.  In my answer to superfrancais, I should have add that I do not think NMDA receptors antibodies are implied in POIS.  POIS is a temporary syndrome triggered by ejaculation, and NMDA receptors are always present in the brain.  If you have antibodies for them in your blood, your symptoms won't go away after a few days, and ejaculation won't change anything to that neither.

Like I have said earlier in this thread, the excitotoxicity effect through NMDA receptors do not implies the presence of NMDAR antibodies, and can be triggered through the innate immune system ( https://en.wikipedia.org/wiki/Innate_immune_system ), through the production of inflammatory cytokines ( antibodies are produced by the lymphocytes cells of that adaptive branch of the immune system ).  This implies that POIS could be more related to a hypersensitivity reaction ( as Dr Waldinger has suggested) than to an auto-immune disease.  Personally, I still think part of the POIS symptoms could be related to a hypersensitivity reaction, and that it can trigger a cascade of metabolic reactions, which I think can finally lead, among other things, to NMDAR excitotoxicity in the brain.  Many POIS sufferers show symptoms of of "acute and temporary" encephalopathy ( https://en.wikipedia.org/wiki/Encephalopathy#Signs_and_symptoms ), so something happening at the level of NMDA receptors can be on the list of the possible causes of these symptoms.   

The relief I personally have with NMDAR blockers, like magnesium, is either due to the implication of NMDAR in my own version of POIS, or because anxiety and other emotional symptoms are at the core of my POIS symptoms, and NMDAR blockers are good at lowering anxiety, whatever the way POIS causes me a surge in anxiety. At this time, the POIS puzzle is still unresolved.
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Quantum

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Re: Could Some Cases of Schizophrenia Be Caused by an Autoimmune Disease?
« Reply #13 on: December 11, 2015, 11:10:50 PM »
I think it's better to focus on the results of the French team since the results are more recent and they just won an award. I could not yet get the scientific paper in question, but in order to understand better I found another vulgarization paper (link below, in French). It seems the phrase "immobilizing the NMDA receptors" has to be taken literally. They have observed, on rats, that these NMDA receptors are moving at the surface of the synapse in healthy rats. And that these receptors are immobilized in rats exposed to a certain kind of auto-antibodies known to cause autoimmune brain inflammation. The capacity of movement is said to be required for the brain plasticity (i.e. its capacity to adapt itself).

http://www.c-yourmag.net/post/2014-08-06/troubles-psychotiques-une-piste-pour-les-comprendre

Bonjour superfrancais,

it is an interesting new notion, for me, this NMDA receptors mobility, discovered through new, modern imagery techniques. 

However, it is unclear if it has any relevance for POIS or not.  I would be interested in knowing if something else than antibodies can immobilize those receptors.  As I said, I do not believe that NMDAR antibodies are present in POIS sufferers blood, because it wouldn't be a self-limiting syndrome, spontaneously disappearing in 3 to 10 days.  Once you have one type of antibody present in your blood, it will always be present for the rest of your life, on a constant basis, and NMDA receptors are always present too, so this should set the stage for a chronic ( constant symptoms), progressive illness, like rheumatoid arthritis or the like.  I have been suffering from POIS for over 37 years now, and it has been neither chronic nor progressive  ( on the opposite, it is far less severe now that I have developed and elaborate method to prevent and control my symptoms).

Even if not necessarily useful for POIS, this article you are referring to is nevertheless very interesting :-)

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