Protocol Serial Paediatrics Omics Tracking in [ME] (SPOT-ME): protocol paper for a multidisciplinary, observational study..., 2024, Armstrong+

Thank you Chris, @MelbME, and team. Great to see this.

I thought this study was well underway? The good day, bad day study in adolescents? Is this just the delay in getting the protocol through the publishing process?

I like the description of ME/CFS in this paper, better than what was used in the (mostly otherwise very good) UK Biobank paper. I noticed you mentioned the twin peak idea in that paper too, here it is in this paper:

I think the evidence for the twin peaks is very weak, and it's not as if there are not a significant number of onsets in people in their twenties, or even in people older than 39. You say that ME/CFS affects individuals in all age groups, so I really don't think mentioning the twin peaks idea (which probably amounts to a myth created by frequent repeating) adds anything.

 

I'm not sure what you mean by 'illness process'. I interpret that as meaning severity, symptoms and e.g. eventual outcome (recovery, worsening) rather than risk factors for onset. The paper has already noted the 'notable female preponderance'.

ref 2 is the Bakken Twin Peaks paper, I don't think it says anything about a sex difference in the illness process, just some differences that they found in the incidence ages.

ref 7 is a paper about the developing adolescent brain and doesn't talk about ME/CFS or CFS at all. Was this reference meant to be somewhere else? (probably the next sentence)

ref 8 is the 2019 UK ME/CFS Biobank study of risk factors. They found that younger age was associated with severity, but they did not report finding that sex was associated with severity or any particular symptomology. The only sex difference they mention is in prevalence, and they note that there are biases that may be inflating that.

ref 9 is
'The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome'
by some of the authors of this protocol. I guess it's a valid reference for the claim, but I couldn't see anything much in the paper that wasn't speculation or a result from small or otherwise weak studies. Of course it's likely that the menstrual cycle affects symptomology somewhat, but I doubt that it amounts to a difference in illness process. Yes, pregnancy may affect ME/CFS, but I don't think we yet have a clear understanding even of what percentage of people improve, what percentage deteriorate, let alone what might be influencing that change. I haven't yet seen good evidence for any sex differences in ME/CFS (other than probably incidence) that aren't likely to be rather downstream of the core disease process.

There's also a great deal written about cortisol in that paper (as well as the latest UK Biobank paper). Please read the commentary here on the cortisol studies that are cited - the evidence for cortisol being a core part of ME/CFS pathology is, I think, unconvincing. Happy to discuss more if anyone is interested.