Incidence age is bimodal for [ME/CFS], with higher severity burden for early onset disease, 2026, McGrath et al

Something I have been wondering about is whether susceptibility might cluster around a regulatory shift that works a bit like a software update.

We are very used to the idea that in other types of animals complete software rewrites are obvious. The classic ones are insects undergoing metamorphosis as pupae, re-writing the caterpillar as a butterfly and tadpoles being re-written as frogs.

We know that the immune system undergoes shifts in things like thymic education of T cells but that isn't really a re-write and the timing doesn't seem to fit. Puberty is a sort of software re-write and so is menopause but again, as already mentioned, these do not seem to fit too well with the apparent peaks. People talk of male menopause but it isn't that obvious.

That leaves the possibility that there might be hypothalamic re-writes that we haven't thought of at all but that might make sense. The transition from responding to environment as a child to responding as an adult is quite big. Another shift in mid thirties might seem implausible but from an evolutionary point of view might not be totally unexpected. People's sleep patterns can change quite markedly in mid life, for instance.

Maybe the immune system itself does not change at these time points but the software for neural responses to immune signals that drives epigenetic changes over days, weeks or months undergoes shifts?
 
Totally anecdotal, but looking at the peaks, I realize that they roughly correspond to two major changes in my own course of disease: something went wrong around the time I was 18-19. This didn't disable me, and I probably would not have met most criteria for diagnosis with ME/CFS, but it did mean decades of feeling off, being heavily fatigued, responding oddly to food and exercise (neither made me feel good nor gave me energy, though I was not prevented from pursuing either), and insomnia, eventually leading me to largely depend upon a mix of stimulants (caffeine, nicotine) and depressants (mostly alcohol) to maintain function and any semblance of a daily activity cycle. Things remained more or less stable until around 40, when they fell off a cliff and left me where I am now. Around each transition point, there were a lot of other factors at play, but the peaks do more or less line up. While gradual onset doesn't seem to be too uncommon, multiple decades before serious deterioration does seem to be quite rare. All the same, I wonder if there is anyone else who had a staged progression and, if so, whether those stages might find any correspondence here.
 
Given that many cases of ME/CFS are triggered by infection, could the onset peaks be partly a reflection of two phases in many people's lives when they are most exposed to infections - when they are at school, and when their children are at school?
 
Given that many cases of ME/CFS are triggered by infection, could the onset peaks be partly a reflection of two phases in many people's lives when they are most exposed to infections - when they are at school, and when their children are at school?
Interesting that Germany is reported here with a later age then other countries given that school ends at an earlier average age of 16/17 in Germany.
 
Interesting that Germany is reported here with a later age then other countries given that school ends at an earlier average age of 16/17 in Germany.

Only for those who don't do A levels. About 10 years ago I think there were some experiments where children would start school at 4/5 years old, but that was reverted back to 6/7. Add 13 years of school (now 12) and a third of students leave school aged 18/19.

And then it depends on the state of course. From Wikipedia: "in Brandenburg, school must be attended until the end of the school year in which the pupil turns 18."
 
@Simon M @chillier this looks really interesting, is there a more accessible format of the paper available anywhere or can someone provide the plain text so I can create an audio version?

It looks like there’s only the PDF and it is sadly formatted in way which makes screen readers or other text to speech very difficult and will take a lot of work to clean up. I’d love to dig into the full thing but for now have settled for the abstract and an LLM summary.
I think we were expecting to publish once they had a formatted web version. That is coming, hopefully soon. I'm sorry this is so inaccessible for you.
 
Are there differences in recommended vaccine policies between countries that might explain the stark difference in early onset reports? Some of the meningococcal strains? In the US there’s some strain-specific vaccines that get recommended for infants and others during teens years or before college, not sure how it is in other countries. Just spitballing to see if anything might line up with the data.
 
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