Genome-wide association study of major anxiety disorders in [Europeans] identifies 58 loci and highlights GABAergic signaling, 2026, Strom+

[Jonathan Edwards]

I thought the B cell mention might be interesting.

The suggestion of synapses in the Zhang paper will probably hold up I think. The anterior midbrain makes sense as somewhere that might be relevant in ME/CFS and my hunch is that all this sifting through is getting us a bit warmer. I am less sure about the lymphocyte clues but they recur.

It looks as if the SNP links for ME/CFS suggest something quite different wrong in this area than in the psychiatric illnesses studied. I am beginning to wonder whether the constant hint of both synapses and lymphocytes, together with the olfactory bit are pointing to cross talk between two systems (brain and immune) that mediate highly complex signalling responses to environment, involving evaluations dependent on memory and cellular cooperation. My idea for autoimmunity was basically that the immune system runs into trouble when recognising molecules that it already uses for recognising other molecules and so on... Maybe these ligand genes have evolved to be used in both systems, maybe as chaperones for business-end steric recognitions.

I am wandering off into random thoughts but I do think the answer must be somewhere in all this. Sitting waiting.

 

[V.R.T.]

cross talk between two systems (brain and immune) that mediate highly complex signalling responses to environment, involving evaluations dependent on memory and cellular cooperation.

This would explain a lot of the more puzzling PEM triggers that esp. severe pwME get.

 

[EndME]

This would explain a lot of the more puzzling PEM triggers that esp. severe pwME get.

In which case it then wouldn't make much sense to me to still think of these things as PEM triggers.

 

[V.R.T.]

In which case it then wouldn't make much sense to me to still think of these things as PEM triggers.

Could you expand on that?

 

[EndME]

Could you expand on that?

In my head: If one would know that the problems come from specific signalling pathways that have gone awry then one doesn't have to necessarily defer to concepts which have historically been perceived as energy related anymore (unless the pathways were to suggest this). To me that means that the problems in severe ME/CFS would not have to be perceived any differently with respect to energy or exertion concepts than how problems in people with epiplepsy looking at bright lights at not perceived as exertion related, but understood at a higher level. I find it possible that many of the problems in severe ME/CFS are probably not related to "exertion" in a meaningful way (similar to how epilepsy is not thought of as a problem of eye lid exertion) rather than specific. If one was to know those specifics there's a chance one could possibly drop the more generalistic concept in the future (unless pathways somehow imply this concept as well or there is an overarching theme on why it has to be kept) and maybe they would become "M" triggers rather than "PEM" triggers?

 

[Utsikt]

If one was to know those specifics there's a chance one could possibly drop the more generalistic concept in the future (unless pathways somehow imply this concept as well or there is an overarching theme on why it has to be kept) and maybe they would become "M" triggers rather than "PEM" triggers?

PEM is just a name, and it already means more than just «post-exertional» «malaise», at least according to our factsheet. It’s a bit like how ME/CFS means something other than «ME» or «CFS».

 

[Kitty]

In which case it then wouldn't make much sense to me to still think of these things as PEM triggers.

Mebbe just triggers?

 

[EndME]

PEM is just a name, and it already means more than just «post-exertional» «malaise», at least according to our factsheet. It’s a bit like how ME/CFS means something other than «ME» or «CFS».

The point is that changes can occur once pathways are untangled. What ME/CFS stands for now is not what it will stand for once pathways are identified. My personal suspicion is that issues in severe ME/CFS will at some point be better described by other means at which point the factsheet may be revisited. I also think that whilst the factsheet is right the practical situation is not yet comparable to "ME/CFS" vs "ME"/"CFS" because whilst some scientists have taken upon themselves to study ME/CFS as symptom based concept, I'm not aware of anything similar happening for PEM (in fact all we tend to see are exercise scientists claiming to be studying PEM and coming up with energy concepts typically without even studying PEM at all).

 

[V.R.T.]

This would explain a lot of the more puzzling PEM triggers that esp. severe pwME get.

To expand, it would explain not just the PEM triggers but the strange PEM symptoms. Light sound, stress and even smell intolerance, temperature dysregulation, other stuff that I literally can't put into words. The way stuff affects you just completely  wrong.

Like watching a stressful film and you start to feel unwell during a chase scene. Or feeling wrong from laughing too hard or being happy. Symptoms arising from sexual activity.

There are so many occasions where it just feels like all then body's circuits are scrambled and it's outputting the wrong response to situations. I can't explain what i mean ironically because im crashed.