Royal College of Physicians article: "Do you really believe in ME?" by Dr Nina Muirhead

I think it's really great this article is published on an RCP website. But there are many other medical professionals who should see articles like this. What equivalent organisations are there for nursing, ambulance crews, etc? They all need to see articles like this, because most of them are wonderful people, yet as naive as Dr Muirhead previously was; it's the kind of article that I imagine they might identify with.

 

Not directly related but relevant to Dr Muirhead’s article, a Tweet from Professor Suzanne Mason MBBS, FRCS, FFAEM, MD, Professor of emergency medicine:
https://twitter.com/user/status/1116105276439109632


I’ve also shared a link to Dr Muirhead’s article with her.

 

Another possibility is transmission of specific pathogens between family members, that increase risk of ME/cfs.

 

there's a difference between a genetic condition (follows one of several different defined genetic inheritance patterns; note that this assumes everyone is either XX or XY, which is not actually the case), and a familial condition (does tend to have a higher incidence in families, but does not follow any known genetic inheritance pattern--doesn't necessarily mean there's no genetic component, but it does mean it's not a single gene and is not as simple as Mendelian genetics).

Further reading:
https://www.untamedscience.com/biology/genetics/non-mendelian-genetics/ (Note: the defined inheritance patterns extend into non-Mendelian genetics, but there are still more known possibilities in genetics, and that doesn't even touch epigenetics)
https://www.differencebetween.com/difference-between-mendelian-and-vs-non-mendelian-inheritance/
https://ghr.nlm.nih.gov/primer/howgeneswork/epigenome

 

This does not seem to fit the detailed incidence pattern very well. If a parent harboured a pathogen it is hard to see why a child should suddenly succumb at age twelve or so. I find it very hard to think of a model of transmissibility that would work. Most pathogens are either endemic (everywhere) like EBV or show up with well-recognised temporal transmission patterns like measles or colds. Hidden agents like retroviruses might give unusual incidence patterns but it still looks a very poor fit.

 

Hmmm. So Suzanne Mason clearly believes there is no need for any NICE guidelines, suggesting they just get in the way of doctors on the spot. Although we all know the ME/CFS guideline is a mess, I think that for a doctor to suggest NICE guidelines are pointless, says much about her opinions.

 

I don't think that is quite how most scientists would use the words. We do not tend to talk of 'genetic conditions', except as a loose term, but if we do it would cover complex polygenic situations if they were the only or more or less only determinant of risk. So ankylosing spondylitis is now thought to be a very largely 'genetic condition' but this results from the effects both of HLA-B gene alleles and cytokine receptor gene alleles and maybe other genes too. It is not Mendelian.

In simple terms I think the difference between a genetic condition and a familial condition is that in the former if you have the right mix of genes, however many that might need to be, you get the condition and if not, you don't; in the latter the genetic risk is not absolute. So for identical twins with a familial condition one may have it and the other not. For a genetic condition the presumption is that they will match.

Nina Moorhead said 'heritable condition' which I think could either imply genetic or familial although I guess we would most often refer to conditions like rheumatoid arthritis as partially heritable.

 

I agree with Barry that the main confounding issue is whether members of a family share environmental factors like a particular style of cooking or playing too many video games or whatever you like. Twin studies are pretty good at correcting for that but it is still theoretically possible for identical twins to have higher shared risk if they wear identical clothes from a factory in the far east that contaminates its products with mercury or something weird like that.

The recent study I referred to was flagged up by Chris Ponting I think through Simon M maybe. I think it looked at twins and found a strong suggestion of genetic risk.

On the other hand we know that the risk for first degree relatives for ME/CFS as a whole is not particularly high - certainly not in comparison to Mendelian dominant conditions.

 

I was not aware that NICE had ever called ME/CFS or FM physical illnesses.

I would expect NICE committees to be made up of people who did not think that was a meaningful category - either because they were BPS or because they are mainstream scientists who consider all cause and effect relations, including mental ones, as physical!

 

I do not think we have a substantial disagreement on this point. Perhaps you did not read my entire post (nor look at my embedded links--as I used the same terms as the NIH in case I did not fully recall the exact terminology from school).

Edit: I did not actually take the "familial" description from NIH. That must be something a doctor said to me recently? I do not recall a term from school.
NIH is calling this "complex or multifactorial disorders" and saying nearly every disease falls into this category.

But the misunderstanding came from missing this bit:

 

Time to create the NIH Metaphysical Illness Division

 

Some people say this as a special case in ME, to reassure listeners that they do not mean that people are malingering, somatizing, or have any kind of factitious illness. I agree that the wording could be better, as I also agree that psychiatric illnesses have a physical basis.

 

HLA variants associated with ME/CFS

 

Sorry for the confusion. I did read through your post several times and was a bit unsure what went with what. It seemed that the quoted bit about non-Mendelian patterns came under familial rather than genetic and that was what I was differing on. Non-Mendelian inheritance can still give rise to a 'genetic condition' in the sense of exhausting the causality.

Complex and multifactorial tends to mean a mix of genetic, environmental and stochastic causal components although it could perhaps be used for polygenic inheritance as in non-Mendelian familial conditions like ank spond (also in a sense a genetic condition) and RA (not a genetic condition since there is a major stochastic component).

 

Answer to question 3 in Q&A with Chris Ponting (https://www.s4me.info/threads/science-for-me-written-q-a-with-prof-chris-ponting.4743/#post-84998): “We know that ME has a biological component (formally: the heritability of ME/CFS is not zero) as well as non-heritable biological causes so this type study is fully justified.”

Guest post by Chris Ponting on @Simon M ‘s Blog: Analysis of data from 500,000 individuals in UK Biobank demonstrates an inherited component to ME/CFS: https://mecfsresearchreview.me/2018...emonstrates-an-inherited-component-to-me-cfs/

 

I would like to see the source of that. People have been looking for HLA associations with ME/CFS for at least ten years, maybe 20 and at least up until a year or two ago there was no definite signal. As far as I know nothing came up on the UK Biobank study that pulled out a prolyl hydroxylase gene. I have a feeling even Simon Wessely looked for HLA associations in ME (or CFS).

 

There was something more recent than that from the USA I thought.

 

Ah!, but the strict definition of metaphysical is 'pertaining to the study of what exists' or 'pertaining to the fundamental questions about existence that underly (are meta to) physics'.

 

Re family connection, In one wing of my family, my fathers side, my dad had a CF/S, very different to mine as no immune symptoms but would meet some criteria, his brother RA, his sister sjogrens, me his daughter ME and my cousin, daughter of mother with sjogrens, lupus. I got significantly sick in my teens as did my cousin though we have different illness, that’s quite rare. We hardly saw my cousin or aunt but genetically, looks/interests I’m very similar to my cousin. I think that the family connection being genetic is pretty strong. In families where multiple children or parent child get it it would make sense if all ate poorly or got same infection but if they didn’t and got Ill at different years I think that likely be biological cause unless you’re blinded by psychological interpretations to these type illnesses as some are. Even if deprivation or stress potentially contributes to poor outcomes within a family, lots of people have deprivation and stress and don’t get severe chronic, physical illness, fortunately.

By physical illness I mean physical symptoms, muscle exhaustion, muscle pain, neurological pain, temperature control issues, nausea and headaches, flu symptoms etc. I think it’s right to call and defend ME as physical and if you don’t you allow psychological or behavioral interpretation to persist. ME doesn’t present as mood or behaviour disorder so AFAIC it’s not psychiatric, it does present with many sickness symptoms. Afaic my illness is as physical as my relatives and more debilitating and it’s helpful to assert that. If my cousin with lupus started saying the use of the distinguishing term was meaningless for her illness I’d think it odd and it seems only in CFS that there’s a call for removal of distinction. Psychiatric illnesses might have a brain or inflammation basis but they present chiefly with mood or behaviour disturbance don’t they, OCD seems to me very different to FM even if brain issues ultimately cause both. Obviously psychiatry and neurology have over Lap but I think that the distinction in presentation for most conditions is useful. With severe ME, if I was in a flare and I had to go to hospital it would be entirely inappropriate to put me in a mental hospital, if I had severe schizophrenia or psychosis and was in a flare up it would be inappropriate to put me in a general hospital.


As there’s the connection, as I’ve suggested in my own family, with other illness groups that’s also important as I think that there’s established family association/increased chance in those.