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

[Jonathan Edwards]

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?

 

[DHagen]

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.

 

[Trish]

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?