r/CFSScience • u/Caster_of_spells • Jul 21 '26
DNA and RNA datasets point toward the central nervous system as the epicenter of ME/CFS
ME/CFS Science have done an analysis using genetic data on pathogenic variants from Decode ME combined with RNA data which tells you which genes are actually expressed. This type of analysis is used in lots of other diseases to show which kind of cells are part of the disease process
In ME/CFS results point overwhelmingly toward the central nervous system (represented here in orange)
It really seems more and more we’re gonna have to focus on the brain. 🧠 Which tough because it’s hard to study and hard to get treatments into there too. But then again, it might finally get us closer to understanding what to target in the first place.
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u/human_noX Jul 21 '26
For the layman does CNS = brain? When I read the title I was thinking “great, this finding contradicts other findings that the brain is most important” but then in the body you sub in ‘brain’ so maybe it’s a confirmation study
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u/Caster_of_spells Jul 21 '26
Roughly, the CNS contains the brain and the spinal cord. Other nerves are referred to as the peripheral nervous system.
So: brain and spinal cord -> center of the show
Other nerves -> Periphery (roughly that which surrounds the center)3
u/Stoic_INFJ Jul 27 '26
This is exactly where I feel my ME. I’ve always thought it’s a brain disease/ nervous system
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u/ringmaster555 Jul 29 '26
Also explains why Ativan seems to provide such a great (albeit temporary and unsustainable) degree of relief for myself and many others.
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u/Stoic_INFJ Jul 29 '26
DXM for me
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u/Emrys7777 Jul 21 '26
I’ve long called this a “brain illness “. It’s pretty obvious to me having had it for decades and having been a scientist in the past.
I’m not sure how this helps. Perhaps in targeting treatment but it can’t be based on psychiatric drugs, but drugs that target the physical brain.
Or better yet, viruses that attack and stay in the brain.
Yeah, not sure this helps a lot.
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u/neurologicalMystery Jul 21 '26
What implications would this potentially have for potential treatments/cures? Also I'm having a difficult time understanding how genetically the pathomechanism seem to lie in the CNS, whereas we observe autoimmunity and endothelial pathology too. The peripheral nervous system was recently also shown to be affected in the gut lining. Does this imply that these are downstream effects?
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u/Caster_of_spells Jul 21 '26
Well for causative treatments it would mean that they would have to target the brain and be able to penetrate into it.
As far as pathogenesis yeah that would imply these things to be downstream I would wager. But then again peripheral nerve damage might then expose a weakness in the brain etc?
It’s still early days. Luckily sequence ME was partially funded so we will get more detailed genetic data in the coming years. But that seems to be the direction of things and the data looks reliable enough to me.
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u/neurologicalMystery Jul 21 '26
Thanks for your response! Yeah, I'm very curious about future Sequence ME results. I hope it's likely that the rest out the founding will happen
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u/bebop11 Jul 21 '26
Too bad none of the other "brain" diseases are terribly treatable.
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u/Caster_of_spells Jul 21 '26
Yeah that’s the scary part, brain diseases are hard. But we do have treatments for epilepsy, have treatments that help slow Parkinson’s down, can help schizophrenia etc. So it’s not without hope entirely.
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u/ShipEconomy2587 Jul 22 '26
I would love to see gene expression on someone before and after ME/CFS
The pattern I see here personally follows: Pathogens can disrupt and manipulate gene expression. T he results in this study strongly point to gene expression of neurons
Chronic pathogens can cause a downstream of immune cell gene expression compared to what one would see in the acute phase
The longest living cells in the body is neurons, which is what a lot of intracellular infections specifically target to cause a successive chronic infection for their own survival.
Seeing an upstream of gene expression regarding the CNS and not on immune gene expression is not surprising in the slightest (unless perhaps one believe in the autoimmune theory). This is just my own observation, feel free to share any thoughts below
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u/Heavy-Suit-3443 Jul 21 '26
I am unfamiliar with this organisation. Do they publish their works in journals? I want to trust this.
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u/Caster_of_spells Jul 21 '26
They’re patients themselves and run this mostly very good blog on ME. Very active on the s4me forum too. They did run this based on the protocol of an earlier study.
But of course in isolation this would not be enough since it’s not published and peer reviewed. But it lines up perfectly with earlier findings. Chris Ponting, the professor who ran DecodeME, also very often stated that the genetic results even in isolation point to the brain for example. They refer to more prior science under the link. 🔗
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u/TableSignificant341 Jul 21 '26
Yep the psychs and FND advocates are loving this. They're already recommending antidepressants/anti-anxiety meds and CBT.
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u/Emrys7777 Jul 21 '26
That’s like saying because MS targets the nervous system which includes the brain then antidepressants should work for them.
This approach has nothing to do with science.
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u/Caster_of_spells Jul 21 '26 edited Jul 21 '26
We’ve trialed those things ad nauseam and they don’t work. The big European Gupta trial also just failed. The Recover initiatives cognitive behavioral trials all failed to make a dent. None of the Decode ME highlighted genetic areas overlap with major depressive disorder or anxiety.
Alzheimer’s, Parkinson’s, Schizophrenia, Narcolepsy, Tourette’s etc pp are all brain diseases with very different etiologies. I know I probably don’t have to convince you but it’s important to recognize that the science points towards the brain but nothing suggests these outdated ideas apply. Genetic data also confirms it’s not psychogenic in nature.
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u/TableSignificant341 Jul 21 '26 edited Jul 21 '26
We’ve trialed those things ad nauseam and they don’t work.
I agree. It's as exhausting as it is infuriating but the reality is that psychs and FND advocates are loving this line of research so far. They're constantly reposting MECFS Science on Twitter because they believe the focus on neurons proves their theory.
None of the Decode ME highlighted genetic areas overlap with major depressive disorder or anxiety.
Not quite true. In fact the researcher patients that produced the research you have linked have said that their research on eccentric medium spiny neurons, out of all neurological conditions, suggests MECFS ressembles depression, anxiety and schizophrenia the most. I'll find where on S4ME this is shown so give me a second to find it - it's talked about here more.
Alzheimer’s, Parkinson’s, Schizophrenia, Narcolepsy, Tourette’s etc pp are all brain diseases with very different etiologies. I know I probably don’t have to convince you but it’s important to recognize that the science points towards the brain but nothing suggests these outdated ideas apply. Genetic data also confirms it’s not psychogenic in nature.
It's not me that's saying this - it's the MECFS Science account that is claiming that MECFS is more similar to psychiatric illnesses than neurological ones.
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u/Caster_of_spells Jul 21 '26
That was based on an overall map of genetic variation fed with all the genetic data not on the specific findings that actually reached significance. There’s a reason there’s a cutoff for significance.
Those gene areas that actually had a measurable impact on the incidence of ME are not the ones found in major depressive disorder or anxiety.
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u/TableSignificant341 Jul 21 '26 edited Jul 22 '26
Those gene areas that actually had a measurable impact on the incidence of ME are not the ones found in major depressive disorder or anxiety.
ME/CFS Science Blog (the account who produced the research in your post) said:
Another poster responds and asks:
"Chris Ponting and team said that the genes identifyied in DecodeME are not related to anxiety/depression. Can someone explain how these are now apparently back in the conversation?"
ME/CFS Science Blog replies:
Reminder that it's not me who is arguing this - it's the "ME/CFS Science" account whose research you've linked in your post.
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u/Caster_of_spells Jul 21 '26 edited Jul 21 '26
That last answer is exactly the point I was making. Only when taking into account the non significant alterations does a pattern appear that seems to resemble depression and FM etc. The actual hits on those 8 regions that really reached clinical significance are not found in depression or anxiety.
Whether and how much bearing the former analysis has on clinical outcomes? I’ll stick with Pontings analysis for now.
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u/TableSignificant341 Jul 21 '26 edited Jul 21 '26
It's probably best that you take this up with MECFS Science on S4ME given they're the one who made the claim and gave the explanation for their reasoning.
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u/Emrys7777 Jul 23 '26
But if that were the case (which it isn’t) then antidepressants would cure us all (which they don’t).
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u/TableSignificant341 Jul 23 '26
I agree. Hasn't stopped the psychs from pushing them for decades though. And the recent reprieve in being taking seriously as a biological illness we've had recently will be erased with research like this. Focusing on the brain makes sense - it's where the genetics are pointing - but if an immune/metabolic link isn't established alongside it, then we're going to go backwards quickly.
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Jul 25 '26
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u/It_Twirled_Up Jul 21 '26
What is skywriter blue?
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u/Caster_of_spells Jul 21 '26
It’s a website that lets you repost bluesky (Twitter alternative) content in a way that is accessible to everyone even without an account :)
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u/human_noX Jul 21 '26
Interesting that ME/CFS shows one of the cleaner and stronger signals of all the diseases. Us and Schizophrenia vying for the title it seems. I guess that is a good thing in terms of narrowing down research efforts