What will a biomarker really give us?

[wabi-sabi]

I've been thinking about this a lot lately, since hopefully we'll have one soon...
My thoughts are informed by having two different things (both ME/CFS and PTSD) because the meaning of a biomarker is so contextual.

As a person with ME/CFS, when I think about a biomarker I want 1) something that will make my disease objectively real, something that will conclusively prove that I am not lazy, crazy, malingering, something that other people can see, recognize and grasp as an explanation. 2) something that will point the way to a cure and give scientists and doctors a handle on how to fix me. 3) an explanation of WHY! and HOW! this happened for myself. Even after all this time, there's still a part of me that thinks I must be making all this up or that I somehow brought it on myself. Seriously, how can all this suffering be down to bad luck?!

As I person with PTSD, I emphatically don't want a biomarker for PTSD. I'm not sure anyone's looking, so probably no worries. I have PTSD because of bad stuff that happened. I'm afraid that identifying a biomarker would imply that my response to the bad stuff was in error. That is, that my PTSD is caused by an internal weakness, a deficiency in "suck it up" rather than an injustice. (Sort of similar to some people thinking fibromyalgia is sufferers just being too sensitive and not having "real" pain.) I'm afraid a PTSD biomarker would put the blame on me, rather than events.

Ironically, the reasons I want a biomarker for ME/CFS are similar to the reasons I don't want one for PTSD.
What do you think?

 

[alex3619]

We have hundreds to thousands of biomarkers already. What we lack is a biomarker or combination of biomarkers that are diagnostic. This is not easy to get and requires a lot of resources be thrown at it.

I'm afraid a PTSD biomarker would put the blame on me, rather than events.

I think it would almost necessarily prove the opposite, that its about real physiological damage. I personally think that PTSD is about physiological damage to the brain.

 

[wigglethemouse]

As I person with PTSD, I emphatically don't want a biomarker for PTSD. I'm not sure anyone's looking, so probably no worries.

There have been studies such as this one that show mitochondrial gene defects have a relation to PTSD (the brain has less energy to function normally)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354348

Many ME/CFS researchers have shown reduced mitochondrial function in ME/CFS as well. It could be possible that they are linked in your case.

 

[wabi-sabi]

Yes, I strongly suspect there are mitochondrial issues in both conditions. What I'm trying to get at though, is the philosophical and emotional meaning of having a biomarker, some definitive test. In terms of ME/CFS, I very much want my mitochondria to be fixed. I terms of PTSD I want to build a just society where trauma doesn't have to happen. Maybe similar physiology, but different root causes, no?

I'm wondering about other people's feelings in regard to a biomarker, because I am struggling and wrestling with my own.

 

[alex3619]

A biomarker for ME is a gamechanger. I think its a huge need. The psychobabblers will suddenly find they can no longer do studies on us, or at least not with any credibility. When tests confirmed MS it changed how patients were treated, though even now some dinosaur docs still want to claim MS is psychosomatic. Public perception changed too. MS is now considered a devastating disease. How patients are treated depend to a large extent on general public perception.

PS In this paragraph I mean diagnostic biomarker, not regular biomarkers which exist in plenty.

 

[Dufresne]

I think it would almost necessarily prove the opposite, that its about real physiological damage. I personally think that PTSD is about physiological damage to the brain.

Obviously it's tough separating the brain from the mind: it's chemistry, inflammation, what that does to one's psychology, how that intern affects the brain, a few lesions, etc. But if you believe the results of the MDMA trials, more than 80% of patients who receive three sessions no longer meet the criteria for PTSD, you might have to conclude it falls more on the side of psychology. Personally I don't believe the drug is working THAT well, but it'll be interesting to see how the therapy develops.

 

[Dufresne]

A biomarker for ME is a gamechanger. I think its a huge need. The psychobabblers will suddenly find they can no longer do studies on us, or at least not with any credibility. When tests confirmed MS it changed how patients were treated, though even now some dinosaur docs still want to claim MS is psychosomatic. Public perception changed too. MS is now considered a devastating disease. How patients are treated depend to a large extent on general public perception.

What ever happened to RNase L? Wasn't measuring for 37 kda picking up 95% of PWME? That along with a clinical case should be good enough for a diagnosis.

I believe "they" want to be able to brush the disease off as long as they possibly can.

 

[alex3619]

What ever happened to RNase L? Wasn't measuring for 37 kda picking up 95% of PWME?

The problem is this is not specific to ME, an issue with most of our biomarkers. So its not diagnostic. It is however one of those hundreds to possibly thousands of markers that show the physiological issues.

 

[alex3619]

Obviously it's tough separating the brain from the mind: it's chemistry, inflammation, what that does to one's psychology, how that intern affects the brain, a few lesions, etc

I have no issues separating the two. There is no evidence mind exists, its inferred. We do know the brain does things, to me the mind is simply the brain doing its thing. Its a description of brain function. It is however steeped in history, going back as far as the ancient Greeks and perhaps before. Mind is not a thing, its a descriptive label. Its so commonly used in everyday speech that we simply accept that its a real thing.

To my way of thinking most psych disorders are brain disorders, and some of the rest are information disorders that are mostly social issues, with the remainder being invented disorders that are really fictional, often for the convenience of psychiatrists rather than patients. The reason why the bioscience on brain disorders languishes is the brain is the most complex thing we have ever investigated, by orders of magnitude, and we lack the technology to advance things at more than a slow crawl.

 

[wabi-sabi]

This is just the sort of discussion I was hoping to spark!
I have to admit, I'm attached to mind as a real entity, and not just a figure of speech. However, I 'd be hard pressed to give any sort of complete and precise definition. But people have been working on that since forever!

Part of what I'm trying to untangle (mostly for me own peace of mind) are which symptoms are which and why some symptoms are amenable to some treatments and not others. For example, my PTSD symptoms were helped greatly by psych interventions. The ME/CFS symptoms, not so much... Really, it was my therapist who kept gently encouraging me ( and me resisting her) to go back to my MD and see what ELSE was wrong. I put that off until I got too sick because I really didn't want another disease in addition to PTSD!

From what I gather from my reading here, that's a opposite experience to what a lot of ME/CFS sufferers have. Lots of other people being told by their medical practitioners their disease was psychiatric (when it obviously isn't) and my therapist telling me my symptoms WEREN'T psychiatric. Ah, the irony. Oddly enough, I'm having more fear and denial about the ME/CFS than the PTSD. I guess that's because I see real help available for PTSD and not much yet (but hoping, hoping) for ME/CFS.

 

[alex3619]

helped greatly by psych interventions

Drugs, or psychotherapy? Drugs might address biology, presuming they work as claimed, whereas psychotherapy can, not will, help with learning strategies to cope.

With ME the main learned strategy to cope is pacing, or limiting activity to well within what can be tolerated, but not too low.

 

[FMMM1]

A biomarker for ME is a gamechanger. I think its a huge need. The psychobabblers will suddenly find they can no longer do studies on us, or at least not with any credibility. When tests confirmed MS it changed how patients were treated, though even now some dinosaur docs still want to claim MS is psychosomatic. Public perception changed too. MS is now considered a devastating disease. How patients are treated depend to a large extent on general public perception.

PS In this paragraph I mean diagnostic biomarker, not regular biomarkers which exist in plenty.

Check this out https://www.omf.ngo/2018/08/15/mohsen-nemat-gorgani/

To summarise, I agree with Alex3619.

Mohsen Nemat-Gorgani is part of a group studying red blood cell (RBC) deformability in ME/CFS. Here's an extract:-
A healthy RBC is approximately 8.0 µm in diameter, which needs to undergo large deformations in order to pass through capillaries, around 2-3 µm in diameter. A slight decrease in deformability has been shown to cause a significant increase in microvascular flow resistance, with important physiological implications.
RBC deformability has been shown to be impaired in various pathologies including inflammatory conditions such as sepsis.

Lets say this group delivered a relatively inexpensive test which separated healthy controls from those with ME/CFS and those with diseases similar to ME/CFS:
A person with ME/CFS would be given a relatively speedy diagnosis;
Someone who tested negative might be given further tests and may even get the treatment they need.I.e. rather that a false diagnosis for ME/CFS;
Those carrying out biological research into ME/CFS could select on the basis of an accurate test. This might help to establish cause and potential treatments. There would be an accurate biological test to assess success/failure of the intervention;
Those carrying out psychological research into ME/CFS could select on the basis of an accurate test. There would be an accurate biological test to assess success/failure of the intervention.

I could go on e.g. a test might identify sub-groups (separate cause/treatments), put an end to inappropriate research/treatments (e.g. pace) and help to increase funding for research.

The only caveat is taken from the film Unrest. We don't want to see a group of those currently labelled as having ME/CFS being told they have tested negative for the biological test for ME/CFS. Therefore, they are suffering from Conversion Disorder.

We won't definitively know the +s and -ve of a test until we have one. I think a test will help many people and will be generally positive.

 

[wabi-sabi]

Drugs, or psychotherapy?

Therapy, actually. I've tried some antidepressants for the pain of the ME/CFS, but they really, really didn't agree with me.

 

[alex3619]

Therapy, actually. I've tried some antidepressants for the pain of the ME/CFS, but they really, really didn't agree with me.

Used appropriately I think therapy can help people learn coping strategies. Used inappropriately it can be more harmful than many drugs. I hope the therapy helped you.

 

[wabi-sabi]

Yes, thanks. The therapy helped a lot. It brought me both coping strategies and an understanding of what's going on inside me. that's one of the things I really need on order to feel better, and one of the things I keep searching for in the ME/CFS. I found it enormously valuable to talk to someone I could trust and who understood. That being said, I can imagine the inverse- how terribly harmful it would be to have desperate and intimate conversations with someone who wasn't trustworthy or wasn't knowledgeable or wasn't compassionate.

 

[Dufresne]

The problem is this is not specific to ME, an issue with most of our biomarkers. So its not diagnostic. It is however one of those hundreds to possibly thousands of markers that show the physiological issues.

I think we'd gain significant ground in the medical world if we included even an imperfect biomarker in our diagnostic criteria.

Take the case of ankylosing spondylitis; if a doctor suspects the disease they'd do a clinical assessment, an x-ray, and an HLA B27 test. Yet HLA B27 is only going to be present in about 85% of cases. That's not as good as the 95% of ME/CFS patients who will have the RNase L abnormality. And of course 8% of the healthy British population have the HLA B27 gene; whereas almost no healthy people have the RNase L issue. So why aren't our doctors ordering this test?

I believe GP's ordering the RNase L test would take us out of the dark ages of this illness. The dark ages of not being believed by our doctors and our families. That would be a game changer. Or it'll do until a better biomarker comes along.

 

[wabi-sabi]

What do you think of the possibility that different patient subsets have different biomarkers?

The only caveat is taken from the film Unrest. We don't want to see a group of those currently labelled as having ME/CFS being told they have tested negative for the biological test for ME/CFS. Therefore, they are suffering from Conversion Disorder.

This is something I think about a lot, but I don't have any good answers for.

 

[alex3619]

We have lots of biomarkers, including 37kDa RNase L, which I was very intrigued with in about 2000 or so. Its a cleaved or truncated protein, and is present in small amounts in most people I think. The issue here goes to credibility. It takes a lot of research, typically well funded, to establish something like that. Doctors cannot just use things like this without risking credibility and legal issues. There is a word for using medical methods that are not properly established but also treating them as scientifically sound ... quackery. Such allegations, even if unfounded, can be damaging to a doctor's career, and interfere with patient care as well.

I have no problems with doctors or individuals using somewhat speculative methods in difficult cases. They just have to be acknowledged as such. This happens with conventional medical practice to some extent ... if a patient has pneumonia they might start on antibiotics and later find its viral pneumonia. Doctors make fast educated guess, and then try to correct as they go.

We have LOTS of biomarkers that are probably diagnostic, not just RNase L. Getting funding for research to firmly establish them is really hard in an area of medicine with few researchers and extremely limited funding. There are a lot of biomarkers currently under investigation as potentially diagnostic.

In the USA I think the FDA has something to do with approving such methods, and they have strict rules ... I am just not sure what the procedures are. Diagnostics research is not something I have found academic and scientific papers on, and I have not deeply investigated it.

We also need to differentiate between clinical use of such markers and research use.

 

[alex3619]

What do you think of the possibility that different patient subsets have different biomarkers?

There are two obvious subsets, and most likely very many more. Those are EDS patients, and encephalitis survivors. Then we have subsets based on specific pathogens, patients with organophosphate poisoning, car accident victims, and so on. We are only just starting to figure out where all these subgroups fit, and there is a long way to go in the research.

One interesting finding is that similar chemistry occurs in other conditions such as sepsis. The ME response might be much more common and far broader than we think. It might be that what we think of as ME is just a special case of a much more common problem. So ME might be broken up into types, or alternative diagnoses, or merge into a larger family of diagnoses, for which something like sepsis might be the prototypical diagnosis.

 

[Consul]

New study from Australian team on biomarkers

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02893-9

Edit: looks like they also have tried to put their TRPM3 findings into context in a new theory, it involves the endoplasmic reticulum which is also the center of a NIH researchers theory coming out of the intramural study.