Autoimmune disease can attack the brain, cause psychiatric symptoms | Hacker News Reader

Autoimmune disease can attack the brain, cause psychiatric symptoms

washingtonpost.com

182 pointsdonohoe131 comments

I'm going to take a wild guess that 90+% of things we describe as 'autoimmune' are in fact initially caused by some bacteria/virus/pollution we haven't yet identified.

I'd like to see research done on mice to reduce the number of viruses and bacteria they are exposed to - for example by sterilizing all air, water, and food for many generations. Then see which ailments go away.

> I'm going to take a wild guess that 90+% of things we describe as 'autoimmune' are in fact initially caused by some bacteria/virus/pollution we haven't yet identified.

As a wild guess probably a bit high but viruses like EBV are being increasingly suggested as causative of many autoimmune diseases.

> I'd like to see research done on mice to reduce the number of viruses and bacteria they are exposed to - for example by sterilizing all air, water, and food for many generations. Then see which ailments go away.

May not be the panacea you expect, on the other hand some people think too clean is the problem.

https://en.m.wikipedia.org/wiki/Hygiene_hypothesis

I think the hygiene hypothesis will turn out to be false, and data pointing in its direction will be the effects of cleaning products.

Yes or volatile organic compounds offgassing from manufactured goods

The hygiene hypothesis makes sense wrt/ potential allergens, less so a "we should let our kids catch every virus under the sun because air quality standards sound annoying to care about"

All the herpes family causes tons of health problems, HSV 1 & 2, EBV, Citomegalovirus .... (some of that problems recently discovered but also the main suspect in many other diseases)

The question becomes why do only certain people get the illness?

50-90% of the US population are EBV or CMV positive yet it’s a much smaller percentage that develop autoimmune illnesses.

I’m the farthest thing from a rheumatologist but it seems like the favored explanation is a combination of infection and abnormal immune response.

At which point could this just be pure random chance? I.e. what if EBV or CMV or similar viruses poking at the immune system are like comic rays hitting non-ECC RAM? Most people won't notice most of the time, and some people will experience mysterious crashes or data corruption that don't seem to have any apparent cause.

Good question, I’m much more familiar with the oncology literature and there is definitely causative evidence linking EBV and to a lesser extent CMV with lymphoma/lymphoproliferative disorders (particularly in the post-transplant setting).

I believe the evidence for autoimmune disorders is much weaker (with the caveat that this is well outside my scope of practice), I’ve heard it being implicated in MS from my neurology colleagues but my understanding is it’s a weak correlation at the moment. I can’t offer more than uneducated conjecture on other autoimmune diseases. UpToDate says the following:

“One difficulty in proving a link between EBV and MS is that serological evidence of EBV can be found in 83 to 90 percent of adults in the Western hemisphere [99,101,102]. On the other hand, EBV seropositivity among adult MS patients is near 100 percent, significantly higher than healthy controls [91,102-106]. Additionally, children with MS are significantly more likely than healthy peers to have serological evidence for prior EBV infection, at an age when EBV seropositivity is much less common than in adults [107]. However, there is conflicting evidence concerning the presence of EBV in brain tissue of patients with MS [108-111].”

SARS 1 & 2

same deal

For similar reasons why ~30% of the population has HSV-1 and never has any outbreaks and don't even know they have it.

I have a thought that only applies to the brain - perhaps mechanical injuries which can allow viruses to cross the blood brain barrier which only happen in a small subset of the population are the ones that are more likely to develop autoimmune disease in the brain. So a car accident which leads to a tear which allows virus into the brain which leads to autoimmune disease that affects the hippocampus which manifest as physical symptoms.

I guess the question is, how do we get rid of them?

We can't. It's likely impossible to completely remove these latent visues from our bodies.

I've been reading into how they establish latentcy and in what cell types. They can infect almost any cell and establish latentcy, they prefer some cells that do not undergo apoptosis, near the brain.

There isn't enough funding in the area either.

Herpes viruses generally. It seems to reactivate on other infections and spread to new cells causing increasing problems in the body. EBV and Herpes seem to hack the immune system to stop these cells from being destroyed. We could do with antivirals that expose these cells or recognise them and destroy them.

I don't think we'll cure HSV.

A drug to limit cell to cell transfer and a vaccine to prevent new spread to other people.

But those living with the virus, it is unfortunate it will remain in our bodies forever, it is just too clever, hidden deep within our bodies in many cell types and impossible to remove without rna editing.

> "I'm going to take a wild guess that 90+% of things we describe as 'autoimmune' are in fact initially caused by some bacteria/virus/pollution we haven't yet identified."

Not directly. Autoantibodies are the direct cause of many, if not all, autoimmune diseases.

It's possible that certain environmental factors, combined with genetic factors, kickstart autoantibody production. (i.e. are upstream of autoimmune diseases, and causative.) But nobody knows for certain. And the reverse hypothesis is also quite popular: An environment that's too clean, that leaves too little for the immune system to do, can induce a restless immune system into producing autoantibodies. "Idle hands"...

And then when they accidentally catch something very mild the whole population is dead because they never developed the means of fighting it.

This is a bit dramatic but many think the RSV crisis was a result of naive immunity due to COVID-19 public health measures.

https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.25582

OR immune damage due to covid itself, which was a more popular theory with more mainstream medical support last time I looked into it about ten months ago.

This isn’t true (that your hypothesis is mainstream), there is no evidence the virus itself was more severe or resulted in more severe illnesses than expected to support the impaired immune system theory[0].

There is endless literature on this but the majority of “mainstream medicine” subscribes to the “every kid got sick at once for the first time” theory[0-2].

Anecdotally, I was working at a pediatric hospital for parts of the RSV wave and my conversations with PICU/ER colleagues was condordant with literature in this space.

[0] https://publications.aap.org/pediatrics/article/149/2/e20210...

[1] https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

[2] https://www.sciencedirect.com/science/article/pii/S147330992...

Thats why you don't do this for humans :-P

But it would help the search to find out which viruses/bacteria/pollutants are harming us, and eventually when they are identified they can be eliminated, for example with a vaccine.

> I'm going to take a wild guess that 90+% of things we describe as 'autoimmune' are in fact initially caused by some bacteria/virus/pollution we haven't yet identified.

Wouldn't it still be described as autoimmune? An autoimmune disease initially caused by an external agent is still an autoimmune disease.

My wild guess aligns with Dr Gabor Mate. Dr. Mate emphasizes the significance of psychosocial factors, including stress, trauma, and emotional experiences, in the development and progression of various diseases, including autoimmune conditions. He suggests that chronic stress, adverse childhood experiences, and unresolved emotional issues can contribute to dysregulation of the immune system, potentially triggering or exacerbating autoimmune diseases.

According to Dr. Mate, unresolved emotional stress and trauma can disrupt the body's natural balance, leading to chronic inflammation and an overactive immune response. He emphasizes the importance of understanding the underlying emotional and psychological factors that may contribute to the development or worsening of autoimmune diseases.

This is a circular argument. If you have an undiagnosed auto immune condition the result of it will be things constantly occurring outside of your control and thus you will have chronic stress which probably will make things worse.

It would only be a circular argument if autoimmune conditions were the only way to become stressed. As it stands, this sounds more like a "vicious circle" (whereby one caught in this cycle has a hard time exiting it).

Is there evidence that stress can occur and not lead to a vicious cycle of inflammation and autoimmune disease?

I am a big fan of Mate, but I think his ideas are oversold if not by him then by many he has “helped”.

> According to Dr. Mate, unresolved emotional stress and trauma can disrupt the body's natural balance

How does that differ from Germanic New Medicine? (see https://rationalwiki.org/wiki/Ryke_Geerd_Hamer)

Come on, really? It differs in that it can cause, not always is the cause.

There is no doubt that stress has physiological effects on body.

>Dr. Mate emphasizes the significance of psychosocial factors, including stress, trauma, and emotional experiences, in the development and progression of various diseases, including autoimmune conditions. He suggests that chronic stress, adverse childhood experiences, and unresolved emotional issues can contribute to dysregulation of the immune system, potentially triggering or exacerbating autoimmune diseases.

Yep, if you read books like 'the body keeps score' and 'the deepest well', the link between trauma and autoimmune diseases AND depression is remarkably high. I'm not saying every case of depression or autoimmune disease is linked to trauma, but wow, is it about as good of a risk factor as smoking is to lung cancer.

I think Dr. Mate raises some interesting theories. Chronic stress is poorly understood and not well addressed in modern medicine (because it’s really hard to study and treat) but:

> is it about as good of a risk factor as smoking is to lung cancer

I wouldn’t go that far. Smoking has a well understood pathophysiology and extensive evidence as it relates to lung cancer.

Quackery.

Modern humans have extremely sheltereled lives compared to our ancestors. Yet, autoimmune diseases seem to be getting more common in modern societies.

> My wild guess aligns with Dr Gabor Mate. Dr. Mate emphasizes the significance of psychosocial factors, including stress, trauma, and emotional experiences, in the development and progression of various diseases, including autoimmune conditions.

Well I had what most would consider to be a perfect childhood and I got Graves Disease at 18 and had to have my thyroid gland fully removed.

So I guess you can count me out of this one.

Clearly a case of subconscious trauma.

There is also a school of thought (don't know how prevalent) that many autoimmune cases are not autoimmune at all. And that the unidentified bacteria/virus/pollution etc. is still present or persisting, so the immune system is continually fighting that hidden pathogen rather than one's own normal cells. And so conventional autoimmune treatments that suppress the immune system are allowing to unidentified pathogen to persist.

Couldn't you tell this apart by the kind of damage caused to one's own cells and what kind of antibodies are present? e.g. https://en.wikipedia.org/wiki/Antinuclear_antibody

Depends on the type and quality of the test. Serological tests can yield incorrect readings.

Ah ANA, the wonderful test that everyone orders and then shamefully consults rheumatology because no one knows how to interpret it[0]. Almost a rite of passage in medical training now.

I jest but I think these tests are still a bit of a mystery (as in why these autoantibodies are made and what their significance is) especially as some people with high titres have no symptoms and vice versa although there is an association.

I think what parent is alluding to is that the trigger for production may be an infection, even if the damage is mediated by one’s own immune system.

[0]for a chuckle this is a humorous but accurate depiction: https://twitter.com/DGlaucomflecken/status/13719013464131174...

And then try convincing your primary care doctor that an ANA test could be negative and you can still have lupus or any other autoimmune disease.

I keep being fascinated by how medicine is simultaneously things like "that death sentence is a minor inconvenience now" and others and things like... this

>although there is an association

A pretty big association I thought

Also what is there exactly to interpret? Or what would a good interpretation look like? I've been to a rheumatologist before and they didn't exactly explain.

Strep is one of those pathogens being actively studied within this context by the PANS clinic at Stanford. It’s been shown to demonstrate “molecular mimicry” whereby its protein signature resembles various parts of our bodies (in the worst case)… with portions of the heart and brain (basal ganglia) occasionally being affected. I suspect there are other pathogens out there that can do the same, but who knows!

Don't autoimmune disorders get WORSE in "cleaner" environments?

If something is common in the environment and would not cause harm to people if not for disproportionate response from the immune system, I would say that the issue is the immune system, not the common element.

Remember that the population of humans a million years ago used to be ~20,000. It is now 7 billion.

Some diseases have big and obvious effects, while others are undetectable/unknown. Assume that diseases mutate a fixed amount per human they infect.

All 7 billion of those people are one 'pool' for disease spread - as evidenced by covid.

That means that the rate your immune system 'sees' entirely novel diseases - not only novel to you, but also novel to all your ancestors - is 350,000x higher than it used to be. The true figure is probably lower, because many diseases infect multiple species. But still, there is a strong argument that we are asking our immune system to do something far outside what it has evolved to handle.

> Some diseases have big and obvious effects, while others are undetectable/unknown.

A disease is a pathological process, something that goes wrong. If someone lives their life without a symptom, they are not diseased.

Your immune system doesn't see "novel diseases", it encounters molecules it doesn't know. These molecules may be pathogenic (i.e. they cause a disease), or they may be harmless. Your immune system reacting disproportionately to harmless stuff, is what's called autoimmune disease.

The part about immune system reacting to harmless stuff is not true.

Autoimmune diseases are diseases in which a body responds to itself. Not to external factors.

Think of it as threat classification errors

Ok. I wasn't sure there was a clear classification of what's external and what's "the body". My point was about making a distinction between disease and the thing being responded to.

we will have to sterilize the air as evidenced since 2020

That's still autoimmune though.

The body has a immune reaction against something foreign - however the antibodies created co-react with proteins found in your own body.

I am not a doctor, but I'm guessing that your experiment would solve some problems and create others. If the immune system has nothing to deal with, it may deal cause more autoimmune problems (see the "hygiene hypothesis").

My expectation is it's mostly environmental pollution like pm2.5 causing inflammatory responses, which trigger immune function unnecessarily.

I base this on the fact that when I moved to a pollution filled city my hair fell out from autoimmune disease, then when I moved out, it stopped happening.

That's not how infection works. You don't clear it up by just stopping exposure. The patients in the article weren't constantly being exposed to lupus for decades. Putting them in a bubble would not have cleared up the infection.

You are making wild guesses from a place of ignorance. If you want to learn more about the science of immunology the resources are out there to learn about it.

Putting them in a bubble for multiple lifetimes might...

Clearly that isn't practical for humans, but for mice, it is, and the results of that can inform further research.

Whoa - the microbiome is hugely important for health in multiple ways. Most humans have about the same number of bacteria in their bodies as their own cells (https://www.nature.com/articles/nature11234). I think the consensus is just the opposite as what you're suggesting - that early exposure to more things is beneficial for a healthy immune system.

I suspect that the culprit is much more likely environmental contamination (microplastics, PFAS, etc), which I guess is one thing that you list. But "sterile" is not the solution, and unfortunately we have pretty badly contaminated the whole planet at this point...

There's a significant psychological factor in many autoimmune diseases.

For example I had asthma and allergy since forever, but I got colitis ulcerosa for the first time when I was 18 and had final exams in the high school, which decided what university I can go to.

Even asthma attack can be caused by stress alone.

Asthma is, of course, an immune system response but is not an autoimmune disease[1]. That said, mental and physical stress are a significant factor in autoimmune disease flare-ups and chronic hypertension is linked (one of many things) to AI disease onset.

[1] https://www.healthline.com/health/asthma/is-asthma-an-immune...

I have to argue against this - humbly as an expert with several degrees in microbiology, immunology, genetics, host-pathogen interaction, university lecturing, etc. The genetic basis of immunology is amazingly complex. To assign 90% autoinflammatory type disease triggered by pathogens is an unfounded assertion. There are many strong examples of monogenic causes of complex phenotypes, while separately the clinical microbiology explanation of many diseases is also perfectly clear. I am certain that there will be many pathogen triggers, as you say, but the number 90% does not make sense based on the last 100 years of the science.

Don't you realize this is hacker news and baseless overconfident claims by random code bros that use "intuition" to argue against well established scientific knowledge trusted by domain experts is mandatory

It's also healthy. "Established scientific knowledge trusted by domain experts" shouldn't be taken for a gospel, even if you're not a domain expert.

Ahh yes, and random 23 year olds who in aggregate thought crypto made economic sense are definitely the crowd who we should trust to point out meaningful holes in that gospel

no.

but there shouldn’t be gospel.

Well, if that kind of simplistic strawman argument is what defends the "scientific consensus", we could do with less of it...

I agree with the general idea, but you should at least state the foundations of your beliefs when you do that though. There has to be some logical training of thought going on.

The Hygiene Hypothesis actually suggests that limiting exposure to microorganisms in childhood might result in worse immune tolerance, leading to a higher rate of autoimmune issues: https://en.m.wikipedia.org/wiki/Hygiene_hypothesis

But I’d say even if it is, it’s because one’s genes are susceptible to it while others won’t have issues

I don't think you can only say germs/pollution. You also have the many elements of "stress" as described in "The Stress of Life" by Hans Selye.

That's... what happens: https://www.science.org/content/article/can-dirty-mice-save-...

I suspect you wouldn't think that if you look into how the adaptive immune system works:

A process called V(D)J recombination shuffles and rearranges the genes responsible for encoding the antigen receptors on T cells and B cells. The cells are then tested for compatibility against your own tissue and cells that match your own tissue are deactivated. So new immune cells are essentially created by fuzz testing.

Once deployed, immune cells that find lots of matches clone themselves amplifying their immune effect.

So an autoimmune problem can be as simple as a newly minted immune cell escaping the compatibility testing or just being slightly reactive enough to your own tissue to cause problems while still inactive enough to pass the test.

With that in mind its surprising to me that autoimmune disorders aren't a lot more common!

Viral reactivation and basically everyone nowadays having a compromised gut microbiome are definitely two large factors in many chronic health conditions.

There's a musician named Ren (@renmakesmusic) who was told for years that he had various psychiatric diseases and eventually it was discovered that he had an autoimmune disorder caused by Lyme disease. He writes songs about his experiences and how he thought his life was over.

He mentioned in a podcast that he only got a proper diagnosis because he lied to a doctor about his symptoms to get specific meds, and those meds just happened to work. Because they worked, another doctor was able to put all the info together and diagnose Lyme.

Lyme disease can be “autoimmune” like in clinical manifestation but is more accurately described as a tick borne infectious disease treated primarily with antibiotics, as opposed to the viruses being discussed here which are more weakly linked and treated with immunosuppressants.

Be careful with anything related to “chronic Lyme”. While it is true that Lyme disease can trigger long-term symptoms, Lyme has also become a catch-all haven for pseudoscience practitioners and quackery.

It has become so bad that most patients with unexplained chronic conditions who use internet health forums will eventually go through a phase where they think they might have Lyme disease. The “chronic Lyme” alternative medicine industry has evolved to cater to these desperate patients by offering convenient, albeit unprovable, answers to the question of what’s causing their symptoms. The chronic Lyme proponents claim that it can’t be tested for, won’t show up on normal tests, or can only be diagnosed through vague symptoms. As a result, anyone showing up with vague symptoms gets a diagnosis of chronic Lyme.

Their proposed treatments usually involve extended rounds of expensive antibiotics which have no proof of working and have not shown any difference from placebo in clinical trials of supposed “chronic Lyme” patients. Sadly, some quick research on the musician you cited shows that he has been taken by one such alternative medicine practitioner and has been attempting to raise tens of thousands of dollars to pay this practitioner for antibiotic treatment. I’m sorry to say but I suspect this musician has been caught up in the chronic Lyme alternative medicine industry without much, or any, scientific basis for the expensive treatments he’s being peddled.

"Leaky gut" is the exact same kind of pseudoscience and quackery

Leaky gut is not pseudoscience. It’s actually a real medical condition called intestinal permeability.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427160/

That’s not to say that any quack can just diagnose you with intestinal permeability without doing any tests, so I agree with you on that.

I think you may be misunderstanding this article. Intestinal permeability is not a diagnosis in this paper, they are referring to the physical permeability of the gut which can be altered in many diseases and is not in dispute (i.e. "altered gut permeability" is a symptom of a disease, not the disease itself).

"Leaky (or permeable) gut syndrome" is not a recognized disease.

No, I did not misunderstand.

Having higher intestinal permeability is a disorder that causes suffering. Call it whatever you want, it increases autoimmunity issues.

https://gut.bmj.com/content/55/10/1512 "increased intestinal permeability is observed in association with several autoimmune diseases. It is observed prior to disease and appears to be involved in disease pathogenesis;"

Right, I don't think anyone doubts that altered intestinal permeability may be seen in several conditions. The etiological theory of "leaky gut" (i.e. leaky gut is the cause of disease) is not accepted in medicine.

This article again suggests a theoretical mechanism that altered gut permeability is involved in the pathogenesis of an autoimmune disease and the evidence cited does not exclude the possibility of a common etiology[0], it also does not suggest the presence of a "leaky gut disorder".

As an aside an association does not mean causation and in any case does not discriminate between symptom vs disorder. A fever is associated with nearly every infection, it doesn't cause it.

[0]e.g. 'These studies provide intriguing data that abnormal permeability may be involved in disease pathogenesis, although they cannot exclude an alternative explanation that mild gut damage (measured by increased permeability) is associated with the development of IBS by another mechanism. ' from the IBS studies cited.

> Right, I don't think anyone doubts that altered intestinal permeability may be seen in several conditions.

Right, so leaky gut is a real issue. If it is a cause or a condition remains to be seen. But to say it is psuedoscience is invalid.

You just keep moving the goal posts.

OP is referring to "leaky gut disorder" that people (quacks) will try to treat today. It is not a recognized disorder that requires or has a treatment so it is correctly classified as pseudoscience (there is no scientific basis for the treatment of an unrecognized disease).

Simultaneously altered gut permeability may be seen with some disorders, significance not yet determined.

I have never changed that position.

Leaky gut = intestinal permeability. Why are you so hung up on the name? I know that the quacks have no idea what they are talking about but that does not mean leaky gut does not exist, in fact they use the term all the time in medcial literature:

Leaky gut: mechanisms, measurement and clinical implications in humans https://gut.bmj.com/content/68/8/1516.abstract

Leaky Gut, Leaky Brain? https://www.mdpi.com/2076-2607/6/4/107

Leaky Gut and Autoimmune Diseases https://link.springer.com/article/10.1007/s12016-011-8291-x

To say that there is no need to treat epithelial permeability is just blinding yourself to possible treatments of immune disorders. I am not saying it is right or not, but saying it is not a "recognized disorder" is not scientific at all.

It just is not a medically recognized disorder/disease/syndrome. There’s no ICD-10 code.

To borrow from Wikipedia which does a better job at explaining the difference in simpler terms (and is accurate in this case):

> “Leaky gut syndrome is a hypothetical, medically unrecognized condition.

Unlike the scientific phenomenon of increased intestinal permeability ("leaky gut"), claims for the existence of "leaky gut syndrome" as a distinct medical condition come mostly from nutritionists and practitioners of alternative medicine. Proponents claim that a "leaky gut" causes chronic inflammation throughout the body that results in a wide range of conditions, including chronic fatigue syndrome, rheumatoid arthritis, lupus, migraines, multiple sclerosis, and autism. There is little evidence to support this hypothesis.”

> “Increased intestinal permeability is a factor in several diseases, such as Crohn's disease, celiac disease … allergic diseases among others. In the majority of cases, increased permeability develops prior to disease, but the cause–effect relationship between increased intestinal permeability in most of these diseases is not clear.”

It is at best right now a finding of uncertain clinical significance. What is being called a disease is pseudoscience pushed by quacks.

> To say that there is no need to treat epithelial permeability is just blinding yourself to possible treatments of immune disorders.

That’s exactly the point. From your first link: “It is still unproven that restoring barrier function can ameliorate clinical manifestations in GI or systemic diseases.“

Because some researcher measured some values in a model or small observational study it doesn’t mean clinicians should recognize it as a disorder and consider treating it outside of a clinical trial.

Interesting, at first I thought you were referring to "post-treatment Lyme disease syndrome" which has some medical legitimacy to it. It appears that there is a distinct "chronic Lyme disease"[0] rooted in quackery, learned something new.

I also assumed the poster was referring to "genuine"(?) Lyme disease (B. burgdorferi infection) which can go untreated and have neurological manifestations.

[0] https://en.wikipedia.org/wiki/Chronic_Lyme_disease

Fun fact: if you have any kind of autoimmune disease, it's easy to get a false positive on certain blood tests commonly used to diagnose Lyme disease, because the less-specific tests can pick up general immune activity regardless of its cause.

I fear for how many people have (falsely) tested positive for Lyme disease, despite never having been exposed, and fallen down a rabbit hole of pseudoscientific treatments while their actual health issues remain untreated. And of course your symptoms will only worsen, which seems to reinforce the need for useless "chronic Lyme" treatments, and so on and so forth.

I know someone who had bipolar disorder until it turned out they just had celiac disease.

It’s so frustrating that the story is actually “new“. We’ve known about neuropsychiatric lupus for decades yet for people like me with disabling mood disorders to get to see a rheumatologist is nearly impossible.

I have bipolar disorder or schizoaffective type and I am also in the initial stages of ankylosing spondylitis and consistent leukopenia, they think it’s a coincidence but I know it’s a mitochondrial disorder. (Complex I and III deficiency)

We’ve gone nowhere in Treatment of mood disorders in over 70 years. My last episode of depression that landing in the hospital. What did they have to offer me? Electro shock treatment. No new tests, nothing.

> they think it’s a coincidence but I know it’s a mitochondrial disorder

Not saying you're wrong, just be very careful assuming you know more than your doctors

> My last episode of depression that landing in the hospital. What did they have to offer me? Electro shock treatment. No new tests, nothing.

Unfortunately there aren't that many tests for depression (I'm aware of none actually). Testing every fringe theory out there (which may well no longer be fringe in x time) is simply not feasible. Saying this as someone currently heavily medicated for depression.

> Not saying you're wrong, just be very careful assuming you know more than your d

This almost sounds like you are stereotyping me...

I do know more than my doctors. For one, they never even know what receptors most of the medication I was taking affected. But also I have my own genetics and I spent the last 15 years studying genetics and neuro-biology. I often fake out researchers telling them I have a PhD and I talk with them with no problem. And I am currently offering assistance to a research study at Stanford who are looking into the possible genetic roots of a specific neurological disorder.

So when I say I have a mitochondrial disorder that is causing multiple issues for me I know what I am talking about [1]. My mitochondrial haplotype is U [2]. I have rare gene changes in ND4 [3], ND4L, and MT-CYB [4} which are all linked to Mood Disorders and I have been treating them mostly successfully with high dose riboflavin [5] (this lowers glutamate [6] witch seems to be the mechanism that helps me most).

> Testing every fringe theory out there (which may well no longer be fringe in x time) is simply not feasible. Saying this as someone currently heavily medicated for depression.

My point is they are testing NOTHING. And these are not fringe theories. I am fighting for you and for my family who keeps wanting to end their life. By saying these are fringe theories you are playing into some stereotype (again). Take a look at pyridoxine for depression, or zinc or iron. These are not fringe theories, they are neglected theories because they would mean the end of treatment. I am not on zero meds but klonopin as needed. I have tried no less than 12 medications that "worked" but left me numb, over weight, and useless.

Please do not give up and let these doctors tell you what the only truth is. I am now working with a family with TRMPSS6 mutations that leave them all iron deficient and oral iron was not helping. They all have severe depression and fatigue and anemia. The doctors gave up on them. Turns out all they needed was to take their iron with citric acid.

[1] https://ibpf.org/wp-content/uploads/2020/02/Andreazza-Duong-...

[2] https://www.sciencedirect.com/science/article/abs/pii/S00223...

[3] https://academic.oup.com/ijnp/article/8/4/515/652752

[4] https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-5618....

[5]

https://headachejournal.onlinelibrary.wiley.com/doi/abs/10.1...

https://pdfs.semanticscholar.org/4948/b1d517ca7333fe0149f5bd...

https://www.nature.com/articles/pr199327

[6]

https://journals.lww.com/neuroreport/Abstract/2004/10050/Gro...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517396/

Having watched my wife interact with the American medical system over the last 10 years for very similar symptoms, I have a much lower opinion of the amount of attention and care the average doctor is able to provide. There have been a few standout exceptions (her psychiatrist in particular) but overall there is little collaboration between the many specialists, and after billing our insurance for a battery of tests, there often little to no follow up.

As a physician I also fully support the not hot-at-all take that we do a huge disservice to these patients and a very poor job with psychiatric and constitutional symptoms/illnesses in general with “good care” being the exception, as you unfortunately experienced.

Just wanted to thank you for coming out and saying that.

Was expecting you to protest but really it wasn't my intention to stereotype you.

I have a Bsc Neuroscience myself but I guess not up to date enough. All I'd heard about Paxil / paroxetine was all negative yet for me it does make a little difference without any side effects at all. Not numb, not gaining weight, although I am curious about what you mean by "being useless"? I feel that way as well, but it could just be the depression. Modafinil helps.

Admittedly I still feel like total shite most days and cry and have very dark thoughts more than I'd like to admit.

Regarding insomnia I thought I knew all the treatments (and tried them, and they didn't work) until I was prescribed Trazodone. Did nothing for the depression but does give me 8-10 solid hours of sleep.

Klonopin I get myself on the black market and it certainly can kick your ass but don't see how that helps against depression since it's mostly an anxiolytic?

The only things that really help are illegal and I guess it just gets me more down in the long run, so round and round we go.

Will def check out your theories & references, thanks for that.

Being useless includes the depression, not really going away, or putting me in a zombie like state that makes me pretty unaware of what was going on around me. I better stay to be in when I was manic for sure, but nowhere to live indefinitely.

I highly recommend you get your genetics and start learning about it all.

There is such a huge, genetic risk and diversity that underpins mood disorders. It is the only way I found myself out of the mess I was in.

I really don’t have an issue with depression as much anymore as I do the mania and insomnia. And the psychosis. That’s where the Klonopin helps me. But lowering glutamate, for some people has been shown to improve stress induced depression.

As for depression, I suggest you look at inflammation an immune system as a regulator. And as for nutrients? I suggest checking your iron panel, B6, and zinc. These will help make the catecholamines implicated to be lower in depression.

> I highly recommend you get your genetics and start learning about it all

What's the best place to do this? I'm in the EU

> As for depression, I suggest you look at inflammation an immune system as a regulator

I made some decisions that sent my life in a downward spiral, I don't think those factors have anything to do with it

> What's the best place to do this? I'm in the EU

I do not know. I am in the U.S.

>I made some decisions that sent my life in a downward spiral, I don't think those factors have anything to do with it

So the difference between psychological depression and biological depression are immense. Not to say that your genetics did not put you at more risk for depression after a stressful event.

It still sucks and I'm sorry. But if it was triggers by life choices I would suggest therapy.

At times I have rapid cycling Bipolar. There were sometimes I would be depressed and manic within four hour cycles. No life situation triggers it. Just noting the difference.

If you're in

Denmark

Finland

Ireland

Netherlands

Sweden

23andme will ship to you.

They ship to many more countries actually, just ordered a kit

Damn, i just want to commend you on the immense amount of research you've done and your rightful confidence of the ailments effecting your body. I have been half heartedly studying my autoimmune disorder for a while but trying to study that while also devoting all of my time to physics degrees is very difficult. I did do some cancer research while my mother was dying but again, i could never approach the actual knowledge of the specialists she was seeing and she didn't want me to worry in the appointments to ask questions. I hope someday to have the incredible knowledge and sourcing that you have as well as the genetic information you've gathered.

Out of curiosity, how did you get your genetic information? Do you have a full set (i forget what they call that) or just a specific part relevant to your research? Thanks

Thanks wholinator2. I have the benefit of being disabled for the last 20 years so a lot of free time. The mania and Asperger's helps as well.

I have two runs of my partial genome from 23andme. One on the v4 chip and one on the v5. Too poor to get my full genome but it is on my radar.

> Unfortunately there aren't that many tests for depression (I'm aware of none actually).

Beck Depression Inventory [0] is one.

[0] https://en.wikipedia.org/wiki/Beck_Depression_Inventory

> What did they have to offer me? Electro shock treatment.

Which State did this take place in?

Electroconvulsive therapy is an evidence-based intervention for certain types of depression. It should be “accessible” in every state although access to psychiatric care is often questionable unfortunately.

>> Electroconvulsive therapy is an evidence-based intervention for certain types of depression.

And evidence that it can cause memory problems and maybe more.

Your point being..?

Every treatment for anything has benefits and harms, there is evidence that the benefits of ECT outweighs the harms in select patients (like those refractory to conventional treatments) so it has been accepted medical practice for a while now.

You certainly wouldn’t jump to put a patient on ECT. This is jogging my medical student memory but when I rotated on psychiatry the patients who underwent this procedure had quite severe and disabling symptoms, it seemed to help although I’m outside of my scope.

It’s certainly accepted in the medical community though.

North Carolina. At a leading university research center...

I'm still reading this recent bulletin article about tDCS - turning that journalist into a sharpshooter and after seeing this: "She said those people have this overactive angry cortex guy just sitting there. When you apply the electric field, it shuts him right up and those people find that their depressive symptoms are alleviated." definitely want to look further into consumer tDCS devices. Presently I've been trying to fix myself by jogging more and drinking less. https://thebulletin.org/2023/05/qa-how-darpa-hacked-a-scienc...

The only reason I have nothing good to say about tDCS for depression is that they still do not know how it works and what they are targeting are if there are any repercussions.

tDCS seems to boost gamma brain waves. That is pretty much where I live according to an the last time I was tested.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491895/

Getting to see a rheumatologist is way too hard. I have a more mundane autoimmune disease (psoriasis/psoriatic-arthritis) and excellent insurance, and it's still a struggle. And then it's a struggle to get authorization for the medication, even with good insurance

I have nearly constant back pain, bone spurs and disc degeneration on my MRI, and a family history of ankylosing spondylitis which required surgery in two cases, and I still can’t see a rheumatologist for some reason. Probably because i am on Medicare.

Where I live, you basically can’t get without a referral. And primary care doctors are clueless about rheumatic symptoms, so they don’t refer.

You’re basically forced to suffer until there is visible irreversible damage (crooked fingers, permanent hunch, eroded joints, eye damage) for them to say “oh shit, yea, you should see someone”.

That’s not to say that the meds the rheumatologist will put you on will treat you any better.

This is common knowledge in the celiac community. Conditions like gluten ataxia are real and serious, which is understood to be distinct from "gluten fog". https://www.beyondceliac.org/celiac-disease/related-conditio...

It is remarkable how I keep on stumbling upon connections between Scizophrenia and Gut Bacterias and it is equally remarkable, the connection now being discovered between Gut Bacterias and Auto Immune disorders. And now when I find such anecdotes between possible connections of Auto Immune disorders and Schizophrenia, it just blows my mind to see how every thing is just connected to one another. This demonstrates just how much we still do not understand and on a more positive note, just how much we can in future.

and yet no viable, actionable treatment has come about from these connections despite them being around for a decade or more

When I hear a person say their thoughts are being controlled by microscopic creatures living inside them, I won't write it off as a paranoid delusion. I'll hear them out.

Agreed, however a massive fallacy in science is that the more people keep repeating “hypotheses”, the more likely you are to be persuaded by spurious results / false positives. With enough attention large scale statistical analysis should be able to define clear causal effects, but we often just see weak results about “maybes” and “might bes”.

As a barely related tangential thought: I've wanted to write a short science-fiction story about an alien life-form slowly colonizing our planet by invading human gut micro-biome through our diet. Through this process they alter our food preferences to choose diets most conducive to their own flourishing and then eventually effect our minds. We become convinced that diet choices are for the benefit of our own health but in reality we are eating foods that really benefit the alien bacteria in our guts.

The idea is very roughly based on the cat poop parasite (Toxoplasma gondii) that is theorized to alter human brain chemistry to change risk-taking behavior.

If this is a causal relationship, how can we explain the apparent heritability of schizophrenia? Some cursory Googling shows 79% heritability found in one Danish study.

https://www.healthline.com/health/is-schizophrenia-hereditar...

We've been seeing stuff like this with COVID-19. Long term, COVID-19 can increases susceptibility to autoimmune diseases, diseases which end up having dramatic impacts on brain health. I know some of the scientists that are having a field day publishing research measuring biomarkers that can predict brain health, and they are absolutely seeing an uptick after COVID-19, and have linked it to malfunctioning immune systems.

Could provide a link to which biomarkers there are increasing? Can they be correlated to the variants of virus and vaccine?

Ok, I misunderstood the difference between an autoimmune disease and immune dysfunctions. COVID can cause malfunctions such as cytokine storms which have a downstream effect of increasing GFAP and NFL, two biomarkers which indicate brain health. If you search long COVID and NFL and GFAP, you should get several studies linking the after effects of acute COVID to increases in these biomarkers. I don't have specific examples though since I didn't read this, I got this from a researcher that's confirmed it in her own (currently unpublished) study and using it to make other observations, I can link you that though when it does get published! That being said I believe articles (like these https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320425/) will confirm as much, I'm just not parrotting any of the findings.

As for variants, Omicron was not as bad I'm told, mostly because Omicron caused fewer people to get severely sick as it evolved to become less deadly. Thus there were fewer immune malfunctions. Vaccines should not have caused immune malfunctions as those malfunctions were induced by COVID making people severely sick, often to the point where they ended up in ICUs.

https://archive.is/vc5Bl

After many doctor fails, a family member resolved their symptoms through diet. Specifically, they follow the plant paradox diet. It's not just microbes that cause autoimmune issues, but also food you eat.

I have no idea if the theory has been disproven, but schizophrenia was thought to be autoimmune because the disease waxes and wanes, like multiple sclerosis and other immune diseases.

Ummm... how is this news? Just ask anyone with multiple sclerosis.

Yeah, that was my first thought as an MS patient. Personal evidence aside, MSers depression and anxiety rates suggests some kind of relationship - as a population I believe we have some of the worst depression rates even controlling for the severity of the disease. We beat out cancer patients, for example.

It pisses me off that psychiatrists and neurologists have no clue about the fact that the disease itself (MS) may cause such symptoms in itself, plus, the fact that your quality of life is worse due to the illness.

> It’s a disease that affects all the brain, including white and gray matters. The neurological lesions begin in early stages and affect all aspects of CNS functioning. MS symptoms include muscle weakness, visual acuity loss, sphincter incontinence, fatigue, anxiety, depression and cognitive deficits.[1]

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933139/

I just had a conversation with my psychiatrist and because the medications do not work for me, she thinks it is not organic. This one last time she also prescribed one of the worst antidepressants (it causes liver damage more so than the others, and taking any medications (such as the medication I take for MS) that harm the liver are a contraindication).

I am not sure why it is not acknowledged, but the disease causes not only physical and neurological problems, but neuropsychiatric as well! I hope you have a different experience with doctors from around there.

Have you ever asked people without MS to describe it?

If you don't know someone who has it, and weren't lucky enough to learn about it in school, chances are you don't really know what it is, or how it can present in a patient.

Neuro is poorly understood in general by a large portion of the population.

IME, most times when you mention "autoimmune disease", people think AIDS. Explaining that your autoimmune disease is kind of the opposite of AIDS, that it's not contagious, are annoyingly common experiences.

And it still amazes me - personally I knew about autoimmune diseases before I ever had one. Probably because of Seal, frankly. The reality is that a large portion of any population doesn't care to learn about anything outside of their immediate lived experience. Easy to forget this when hanging out on HN and having a nerdy and wonky social circle.

It is not news to us, but my neurologist (specialized in MS) and psychiatrist have no clue about the fact that the disease itself can indeed cause depression and anxiety (or any other neuropsychiatric symptoms[1]), and this is not even mentioning the perception of the disease itself along with its symptoms such as difficulty walking and the like.

According to my personal experiences, these doctors are clueless. I have been told that the tremor in my leg will never be cured, yet it disappears after taking Kratom. It is also much less frequent now after I have done some exercises for some time now, along with a massage that I receive once a week.

By the way, I do not wish to talk about this touchy subject, but I know someone who works at a social home and around 80% of the patients have gotten worse after having received the 4th booster. That, and in general, after COVID-19 and COVID-19 vaccines there have been many more people who have been diagnosed with MS, most likely from either COVID-19 or the vaccine. It is known that those vaccinations may cause autoimmune diseases (check PubMed). Personally I have received the diagnosis long before COVID-19. At any rate, this is why I was reluctant to get the vaccine. As far as I know, I never had COVID-19.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933139/

Why did it take them 20 years to notice the autoimmune disorder?

The following video conference with Robert Lahita is one of the more substantive discussions on the understanding of systemic lupus erythematosus (SLE) that I've seen in a while.

https://youtu.be/FYYfHWR7WwY

In his presentation (~36:20) he has a slide stating that *67% of those with SLE have psychological or psychiatric issues*, 8-20% seizures, 3-16% cranial neuropathy. Of course, "psychological or psychiatric" could be depression and anxiety, and I don't mean to minimize those issues at all, but cognitive dysfunction is a bear in the room for all SLE patients and probably far more serious if one is unlucky enough to have that symptom manifest (most do not, as I understand it).

I will say that at disease onset and adjusting to having a disease, depression is common. It's life-changing, so to be expected. Ongoing, I think it's a constant battle as you're constantly reminded of limitations and pain is like an everyday companion that you learn to live with but sometimes the mental load can get overwhelming, triggering episodic depression. I know this from personal experience, but also my exposure to others with SLE and MS. As you go, it can be hard to know whether some mental and attitudinal issues are related to SLE and its side effects or just aging (e.g. increased anxiety, timidity, depression, memory loss, mental fog, fatigue).

And speaking of mental load, blocking out chronic pain takes a lot of mental energy, which is a zero-sum game - it indirectly results in a decreased ability to focus, engage, etc.

Regarding other comments here:

1) There are well over 200 identified "autoimmune disorders", and any amount of research that's compelled by having one of them will reveal how much and ironically how little the scientific community knows about causes, dynamics, and treatments for autoimmune disorders. In fact, the immune system itself is monstrously complex and it's amazing how mysterious it remains considering how much really is known about its mechanics.

2) Animal models for SLE (and I assume most autoimmune disorders of the same severity - not talking allergies and asthma here) are traditionally hard to create and have faith in, though this has been getting better. It makes sense that this has been challenging considering we don't know specific causes.

3) Pathogenesis - Environment (UV light, drugs, viruses, pollutants, etc.), hormones/epigenetics, genetics, stochastic factors (chance), comorbidities (e.g. hypertension), all seem to play a role, and none seem - on their own - to be good predictors of risk. It's thought that there's some "trigger" in the sense that all these factors reach some threshold that cause breakage in the system at a point in time and BAM! now you have Lupus or MS, for example. So it could be that you get infected with something and experience an extraordinary level of physical and mental stress at the same time, and it tips the scales. But on their own neither of these factors would be causal, and even together these wouldn't necessarily have the same impact on you at a different time in life or affect another the same way. Clearly there are missing links here.

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