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Comment by jessriedel | Hacker News Reader

Is there evidence of a well-defined physiological mechanism rather than merely being a symptom cluster that might be purely psychological? Some brief Googling suggests that CFS is sometimes precipitated by various viral or bacterial infections, which is a step in the right direction, but I haven't read anything yet that rules out the alternative hypothesis that this is a (cluster of related) psychological disorders that is sometimes prompted by a life event. The dozen patient organizations campaigning for recognition is a bit of a red flag.

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I'm a celiac and it is pretty annoying to hear people suggest something is psychological or (as it is often put) placebo. What makes it a red flag that people want recognition for a condition? Does it make them snowflakes if they want people to be aware that they are sick in a way that other people don't regularly experience? I would love for some recognition to the idea that food can make you sick, as I'm sure people with CFS would like awareness, more research, and solutions to their issues. Until you have evidence that it is purely psychological I would refrain from suggesting such.

> Until you have evidence that it is purely psychological I would refrain from suggesting such.

If there are a bunch of self-reported subjective symptoms with no biomarkers or any established physiological mechanism, I believe the null hypothesis would be psychological. (This is why, for instance, the symptoms of grief would be considered a psychological condition absent evidence to the contrary.) You might have specific arguments and evidence for having a different prior in this specific case, in which case I would like to hear them.

> What makes it a red flag that people want recognition for a condition?

People stand to gain socially and economically from having their symptoms classified as a physiological disease, so they are less likely to approach the evidence dispassionately. When much of the discussion online is provided by such advocacy group, we ought naturally be suspicious.

The issue here is that you did some "brief googling" (your words) on a complicated, confusing, cutting-edge area of clinical research, and now feel competent to state your completely uninformed "null-hypothesis"...

Here's some basic information:

https://www.cdc.gov/me-cfs/index.html

https://www.nih.gov/news-events/news-releases/nih-announces-...

http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS/MEC...

I've seen those links. Is there some particular evidence you're pointing to? Or a position statement by experts concerning a convincing physiological mechanism?

You've seen those links? Have you read them? The third one is a link to the most extensive literature review ever undertaken, and their conclusions were strong enough for them to state flatly in the abstract that this is not psychological or psychiatric.

https://www.ncbi.nlm.nih.gov/pubmed/25695122

I'm left wondering exactly what it will take for people to back off this stuff about this being a psych illness. What evidence exactly is required? The volume of studies indicating objectively measurable biological abnormalities is massive. Many are unreplicated due to longstanding funding issues. But while I think most reasonable people would agree that psych issues and/or stress are capable of causing a number of physical issues, I can't imagine we'll ever see anything that suggests that psych issues could possibly come close to affecting the body in the severe ways that Myalgic Encephalomyelitis does.

https://app.box.com/s/9s4coexxtys5bnz33i6gvqqygu67ex5o

> You've seen those links? Have you read them? The third one is a link to the most extensive literature review ever undertaken,

I did read those links. The first two conspicuously did not make a claim about a physiological origin, and the third gave a "report" link that led to a paywall.

https://www.nap.edu/catalog/19012/beyond-myalgic-encephalomy...

> and their conclusions were strong enough for them to state flatly in the abstract that this is not psychological or psychiatric. https://www.ncbi.nlm.nih.gov/pubmed/25695122

Thanks! This new link was super useful, and is probably the strongest evidence available on this thread. Do you think that the CDC would endorse the claim about physiological origins in this report? (It's from 2015.) It's notable that the report introduces yet another name and set of defining criteria. As far as I can tell this report does not yet reflect an expert consensus, but I've updated my opinions significantly.

> I'm left wondering exactly what it will take for people to back off this stuff about this being a psych illness.

Can we agree that, given the social and economic implications, there is a huge demand from patients for doctors to issue a diagnosis for various collections of self-report symptoms (not just CFS/ME/SEID)? And that this leads to the potential for bias in the system? Are you not unsettled by the fact that the report you link admits that replication and validity are still big open problems?

I'm generally very worried with the anger and political bent to this thread (though your comments in particular have been very productive and are much appreciated). It just seems more productive try to convince skeptics based on the merits of the evidence, and admit when there remain significant disagreement and uncertainty among experts.

jessriedel, the consensus is that this is a physiological disease with an unknown mechanism. That's why it's an area of active research.

I don't know where you get the idea that the null hypothesis for the cause of any set of symptoms not explained by known biomarkers needs to be "psychosomatic disorder". That's not even wrong - it makes no sense.

> the consensus is that this is a physiological disease with an unknown mechanism

Can you point me towards a statement of that consensus?

> I don't know where you get the idea that the null hypothesis for the cause of any set of symptoms not explained by known biomarkers needs to be "psychosomatic disorder".

I didn't say that, and in particular never used the words you put in quotes and attributed to me. However, I'm pretty comfortable with what I did say: absent evidence to the contrary, a collection of self-reported subjective symptoms with no apparent physiological counterparts is significantly more likely to have a psychological origin. Can you say more about why it doesn't make sense to you? Or point me towards the evidence specific to CFS/ME that makes you think it doesn't fit that description?

Myalgic Encephalomyelitis is not a collection of self-reported subjective symptoms. It never was. Currently the CDC has adopted criteria for which post-exertional malaise is a required symptom. This is measured by 2-day CPET as mentioned elsewhere. I realize that a lot of people don't keep up on this stuff as much as those affected by this illness, but I have to say that it gets a bit tedious having to correct these commonly held, incorrect perceptions about what this illness is. Chronic Fatigue Syndrome is 'tired all the time,' 'fatigue,' sore throats, headaches, muscle & joint pain. Ramsay ME is closer to 'deathlike paralysis.' There's a reason why it was once described as 'atypical polio.' And as has been pointed out elsewhere, while a person suffering from depression is likely to respond positively to exercise, an ME patient responds so negatively that it is to be considered contraindicated, in the strongest possible terms. That's why the Institute of Medicine recommended renaming it to describe exactly what exertion does.

There are even objective tests for pain based on heart rate response to exertion

The choice isn't binary physical or psychological.

No biomarkers? How about: currently unknown biomarkers. And why the preoccupation with biomarkers anyway? What are the biomarkers for phantom limb pain or PTSD?

A suggestion: spend a few months working with, listening to, and helping people before publicly declaring that you've got the measure of their problems.

First I want to say that determining something as Psychological doesn't put you in much better of a position than just saying something is a somatic condition we just don't understand yet. Secondly, to sufferers who are upset by this idea, please don't be. Yes, when the vast majority of people hear that a condition is psychological, they somehow think it's easier to deal with, less real, madeup or somehow not physical. This is wrong and any good physician will treat you with the exact same empathy and respect whether they believe something is psychogenic or somatic.

Ok, with that out of the way, the answer to your question is yes and no. Some folks emphasize the comorbidity of ME/CFS with depression to try and establish ME/CFS as a psychogenic illness. Some cases of CFS improve with the introduction SSRIs. Which further embeds this belief. But its entirely possible that the depression is a result of the day-to-day suffering. And the improvement reported with SSRIs isn't just a result of the sufferer's generally improved disposition.

The main difficulty with CFS is that it is currently a bucket diagnosis. So, you end with people in that bucket that have other diseases. For example, there are probably a good number of people in the CFS bucket that have an autoimmune disorder like Rheumatoid Arthritis or Spondylopathies because the mechanisms of diagnoses for these are somewhat unreliable and the effects of treatment are purely subjective if blood tests are consistently normal.

Without some differentiator, it's really difficult to study the condition with confidence. Any effect or symptom sampling will be diluted if our bucket has multiple diseases in it. It's because of this that I think sufferers should resist the temptation to pitch their tent around the CFS flag. But I do understand the yearning to have a name by which to call your affliction.

Thanks, I agree with basically all this. I would only mention that medicine has a better track record of developing treatments to disorders with a somatic cause than purely psychological ones.

"Comorbidity" - but which causes which? Depression can absolutely lead to fatigue. But if you were healthy, and suddenly you have absolutely no energy, and your brain is fuzzy, and you're sleeping 14 hours a day and still don't have any energy the other 10 hours, well, that's depressing.

This is why I wrote...

> But its entirely possible that the depression is a result of the day-to-day suffering. And the improvement reported with SSRIs isn't just a result of the sufferer's generally improved disposition.

Though I meant is where I wrote isn't there.

Note to self: Read more thoroughly next time...

Mea culpa.

It is not generally true that physicians will treat people with somatic diseases well (or at all) if they personally believe symptoms are actually caused by psychological issues.

This is an unproductive, even dangerous thing to tell sufferers.

ME/CFS is an under-researched, multi-system disease that affects people in a multitude of ways and is very hard to diagnose. There are no accepted bio-markers yet. There are, however, many well-respected researchers in the field, and more are beginning to enter it from all kinds of disciplines. Basically none of them think this is a psychosomatic illness. This is a good place to start for getting an overview of interesting current research: https://www.omf.ngo/the-end-mecfs-project-2/

Wouldn't the researchers entering this field be selected for thinking this? Their opinion seems less useful than, e.g., a position statement by an encompassing field.

I'm not sure what you mean by "position statement by an encompassing field."?

"Position statement" = collective statement by a group of experts on a topic. "Encompassing field" = group of medical experts who study a larger body of knowledge that includes CFS/ME as a subset.

Like, in physics there is a big field of people who study dark matter, with subfields who specializes in certain (often mutually exclusive) hypotheses about what dark matter is made of, e.g., WIMPs, axions, etc. If I wanted to know whether a new hypothesis about dark matter was plausible, I'd want to hear what all the dark matter specialists thought, not just people who already committed to studying that particular hypothesis.

That might be why its labeled a syndrome. In medicine, syndrome vs disease is exactly the distinction you're making.

Syndrome refers to a set of symptoms, whereas disease is both a definite pathological process plus a set of symptoms caused by it.

The “ME” is part of the name now for a reason. They have more information than symptoms alone. ME is the newer name for it, but CFS has been the more commonly used term.

Title for post should be “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Initiative”

>ME is the newer name for it

No, actually ME was the old name which was coined in the 1950s. It was eventually dropped in favour of Chronic Fatigue Syndrome in the 1990s when it was realised that there typically wasn't brain inflammation, and there wasn't always myalgia.

The term ME was resurrected recently because it is more appealing to some patients, implying a more severe and physical illness.

Incorrect. There are going to be studies showing that inflammation in the pipeline soon, but for now there is the Japanese paper from 2014. You know of it, Mr. 'research.' Melvin Ramsay & his colleagues didn't pull this out of thin air and you know it. Plus, the canard of 'it's more appealing because' is stuff and nonsense, much like the fanciful notions of how much damage stress can actually do. You're on the wrong side of this.

The Japanese study [1] looked at immune (microgial) over-activation in the brain, which is different from actual inflammation of the brain or spinal cord (encephalitis or myelitis). Stress, anxiety and depression from psychosocial stressors are already known to cause neuroinflammation from microglial over-activation [2].

It is a little confusing that they use the term neuroinflammation for something that isn't really inflammation.

[1] http://jnm.snmjournals.org/content/55/6/945.long [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660717/

The current gold standard test for chronic fatigue syndrome is repeated cardio-pulmonary exercise test (CPET).

http://www.shoutoutaboutme.com/testing/the-2-day-cpet-a-gold...

Unfortunately, research into this disease is hugely underfunded relative to its societal impact. Even if it is a biopsychosocial condition, which I highly doubt, its effect on millions of sufferers begs for proven solutions. One of the more promising avenues currently is the metabolic trap hypothesis:

https://www.healthrising.org/blog/2018/10/18/the-metabolic-t...

I've suffered from CFS for 17 years, and spent 13 of those looking for a psychological solution, since all my blood tests were fine. Finally accepting the physical nature of my condition has led me to pacing my exertions so as to minimize my symptoms, which is a huge improvement. I would be completely willing to accept a psychological cure today if it actually worked. The best biopsychosocial research is the PACE trial into CBT and graded exercise therapy, which has been highly controversial in its methodology, but even taken at face value, has shown only marginal improvements, and certainly no objective end to disabling symptoms for any significant number of sufferers. (I'll let you look that one up since most sources are highly biased either pro or con.) I myself have tried both CBT and GET multiple times with no improvement in my condition.

Thanks! This was the most useful comment I've received.

> Even if it is a biopsychosocial condition, which I highly doubt, its effect on millions of sufferers begs for proven solutions.

Definitely agree. The only caveat is that reliable, robust psychological interventions are harder to come by.

Anecdotally I used to think that sufferers of Chronic Fatigue were suffering from psychological issues. Earlier this year I was diagnosed with EBV that led to a post viral illness (the first step in EBV becoming Chronic Fatigue). I saw a number of medical specialists and I would them that their diagnosis doesn't make sense. I'd never even heard of illness leading to Chronic Fatigue. Luckily I recovered, or am nearly 100% recovered, but it changed my mind on the illness.

> Is there evidence of a well-defined physiological mechanism rather than merely being a symptom cluster that might be purely psychological?

Is there evidence of a well-defined psychological mechanism rather than merely a symptom cluster common to autoimmune diseases and various other immune system disorders?

There seems to be a lot more evidence supporting CFS as an autoimmunity than any other avenue for explanation. It appears to be comorbid with numerous kinds of poor immune function, and often occurs after viral infections, frequently Epstein-Barr (so much so that one of its possible incarnations was even called "Post-Viral Fatigue Syndrome"). And like most autoimmune diseases, it favors diagnosis in women.

As one paper puts it as clearly as possible: "The continuing debate as to whether myalgic encephalomyelitis or postviral syndrome is predominandy organic or psychological is unhelpful." And that was in 1990; we're even more clear that it has its roots in biology now. The medical community is at a consensus that there's an organic cause, they just don't have enough data collated or a good enough understanding of the immune system and its interaction with the disease process to know what it is. And that's not surprising - rheumatology in the context of autoimmunity is one of the youngest branches of medicine and our understanding of autoimmunity is very much in its infancy. Lupus was known about for centuries, but only conclusively proven to be an autoimmune disease in 1948-49.

Frankly, at this point, with all of the collected evidence, over 9000 different scientific papers and three world-recognized medical agencies (the CDC, the NIH and the Institute of Medicine) in agreement that it's biological, suggesting it's all in the hundreds of thousands of sufferer's heads is pretty insulting. Maybe go educate yourself on the topic before lobbing such accusations?

> Is there evidence of a well-defined psychological mechanism rather than merely a symptom cluster common to autoimmune diseases and various other immune system disorders?

Are you asking if all autoimmune diseases can be detected by a single test. That doesn't really seem relevant. To my knowledge, all of the diseases that are confidently attributed to an autoimmune disorder do indeed have corresponding physiological evidence, with higher degrees of confidence when there are independent pieces of direct evidence. (One can imagine a case where there was overwhelming circumstantial evidence instead, but I've never heard of it; maybe you have an example in mind?) Autoimmune diseases generally have multiple common physiological features like excess inflammation, responsiveness to steroids (which suppress the immume system), or antinuclear antibodies (ANA).

https://www.mayoclinic.org/tests-procedures/ana-test/about/p...

The rest of your comment was much more helpful. Thanks! (Except for the part where you said I made accusations. I didn't.)

> Lupus was known about for centuries, but only conclusively proven to be an autoimmune disease in 1948-49.

Right, there are obviously lots of physiological diseases whose underlying causes aren't understood for a long time. But Lupus had objective (non-self-report) symptoms, giving doctors confidence in it was physiological. They were correctly unsure it was autoimmune until later evidence became available.

> The medical community is at a consensus that there's an organic cause,

Could you link to a consensus statement? I looked around a lot and all the documents i could find that reflect a consensus of experts like the CDC (rather than the opinion of individual researchers) were careful to never endorse a physiological mechanism, even an unknown one.

https://www.nih.gov/news-events/news-releases/nih-announces-...

https://www.cdc.gov/me-cfs/about/index.html

> ...they just don't have enough data collated or a good enough understanding of the immune system and its interaction with the disease process to know what it is

Sorry, are you saying there is a consensus it's autoimmune, or just biological? There appear to be lots of non-autoimmune theories too.

>in agreement that it's biological

Actually, everything is biological, including depression. The CDC, NIH, etc. are in agreement that the illness is real, and not malingering or hypochondria. But they are open-minded to the etiology.

>suggesting it's all in the hundreds of thousands of sufferer's heads is pretty insulting

Nobody is suggesting that it is imaginary.

Yes. Something called “post exertional malaise” which can be tested via the Stevens Protocol.

In short, given the same exercise test two days in a row, normal people behave the same (slightly better even) but CFS patients degrade substantially.

A variety of other tests such as tilt table tests, Cardio Pulmonary Exercise Tests (CPET) and Advanced Invasive CPET are also able to diagnose physical symptoms, and sometimes even treatable sub-sets of the condition.

Mitochondrial dysfunction is present in the vast majority of people with the condition.

That hasn't been replicated yet, and even if it was it wouldn't prove that the cause isn't psychological.

https://www.sciencedirect.com/science/article/pii/S104327600...

"The exquisitely orchestrated adaptive response to stressors that challenge the homeostasis of the cell and organism involves important changes in mitochondrial function"

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