This is why every attempt to try and determine a specific cause has failed, because so many things can cause biological/physiological stress on the body and different people will be more susceptible to different things. Every person, with their individual genetic makeup, current health as well as their health and environmental history, etc. has more or less sensitivity to certain stressors, has a higher or lower total stress burden that they can withstand, and can withstand it for more or less time compared to others.
Person A might be very sensitive to certain environmental toxins more than Person B, while Person B because of a previous illness as a child might be more sensitive to certain viruses, etc. You get what I'm talking about.
When enough stress burden for enough length of time is put on that particular person then they hit the tipping point and fall into ME/CFS or potential other chronic related diseases.
I regard this as a possibility, but only a possibility at this point. Its something we should be thinking about though.
There is no question that some people are more vulnerable to some issues than others. Causes range from genetics, epigenetics, toxin exposure, diet, comorbidities, and indeed anything that induces alterations in function expressions of genes.
There are many possibilities as to why the cause has not been discovered. First, it might have been discovered, but we missed it. This is entirely plausible, just look at the 65 years we failed to realize CPET was a good test in ME, aside from the very few researchers who were working on it, and the small number of doctors who followed that research.
Second, it might be something we do not understand yet, or cannot measure. We cannot presume the science is complete enough to include every possible cause.
Third, there may be many different causes muddled together on the basis of a similar final syndrome. The evidence is strongly suggestive that ME is two diseases, not one, but this does not rule out one disease with two different disease expressions. Different disease expression groups are known in other diseases. (This is of course ignoring the heterogeneous hodge-podge of CFS diagnoses.)
When you look at neurally mediated hypotension, especially those who become bradycardic not tachycardic, then you realize there are two response groups to any demand for sympathetic compensation to cope with lowered blood pressure in the brain. The one we hear about a lot is POTS, in which the heart races. The other one, a group I am in, has a massive slow down of the heart, and can lead to the heart stopping. This is a parasympathetic response, not a sympathetic one. Its a big percentage of us. So all that can be said is that either there are two subgroups from two different causes, or again two different expressions of an underlying cause.
The tipping point idea is covered in both catastrophe theory and chaos theory. Its a general mathematical expression. Its probably right, but again the real question is mechanisms. How do we test probable mechanisms? Simply showing there is data that might support a particular view is not enough. This is general problem in much of medical research, and particularly psychiatry. Things do not get tested.
What predictions of a particular model run counter to the current models, and how do we test for them? Thinking of tests, and testing, is useful, because if something can be demonstrated that was not expected in other views its a good basis for evidence.
Low blood volume on the other hand is a topic that has been inadequately explored, and for which the research is sparse. Its one of the things that has not appeared interesting enough to have research funded. Much of which is written is speculation. We know it exists, we know its common in us, but we do not understand it. I find this deplorable.
Th1/Th2 dominance tends to be stable unless perturbed, or at least that is my current understanding of it. Both cause a shift in immune cell subtypes, and the cytokines from those subtypes maintain the immune status. Of course the notion of Th1/Th2 is coming under a lot of fire, as its highly possible that this is an artificial distinction, and the debate in immunology is ongoing. Even Th1 and Th2 is looking too broad and vague, and over-simplification of something very complex and dynamic.
I found your posts interesting and am fine with you using the term stressors (as indeed Rich Van K did). One thing I am not understanding is that you say the Th1 deficiency could be caused by raised catecholamines but you also say that they may only be raised in the beginning of the disease...so what would continue to cause immune imbalance after the catecholamines have dropped?
