It seems widely accepted that “stress” leads to inflammation. “Stress” in this context is always used to denote emotional stress. How does emotional stress lead to inflammation? Is there evidence of how this pathway works? Thanks in advance.
That is not something I recognise as someone who worked in inflammation for 35 years. Who would you think accepts this?
I am so pleased to read your post @Jonathan Edwards. It makes no sense to me. And yet every slightly-less-scientific page I read (web, print, whatever) on inflammation notes that decreasing “stress” (emotional) helps reduce inflammation. I wondered for a long time if I was just not reading the “correct” scientific literature, but now I am thinking it’s not me who is ignorant.
Since neuroinflammation is one of the many theories as being the cause of depression emotional stress is the missing link. Thats sarcasm, i don't know if it does and would be surprised if it does.
It all began with Hans Selye. One of these days I'm going to read the relevant literature. I think it may be possible that these experiments (like Beecher's work on placebo) may have led to misleading or exaggerated conclusions. Because people keep trying to treat disease by treating stress or psychological factors and the results seem to be consistently disappointing. https://en.wikipedia.org/wiki/Stress_(biology)#History_in_research
I think it's correct to say that this began with Selye, even if he focused on the endocrine side of things. Later on other work was done examining cytokine response to stressors and presumably that's where the stress leads to inflammation narrative comes from. My initial feeling (or prejudice), is that this technically correct but probably taken to be more important than it actually is. So, actually looking for relevant studies, I found this: https://www.ncbi.nlm.nih.gov/pubmed/19446599 Looking at this, I wonder if any differences could be explained simply due to differences in exertion. The control group did reading instead which is considerably less demanding than preparing and giving a speech and then doing math. That's a weakness that could invalidate all of their conclusions.
@Jonathan Edwards I've had eczema on my hands for most of my life. As a teenager at school and a student at university, upcoming exams would send the eczema crazy. Sometimes I could barely bend my fingers, and the skin would crack and bleed if I tried. My fingers were often swollen. Inflammation ran rampant. Once exams were over the inflammation and skin soreness would slowly fade back to my usual level. I've suspected in recent years that the stress of the exams might have been increasing my cortisol and adrenaline, and that was the source of the worsening of my eczema and the associated inflammation. Is that likely?
This 2012 article https://www.sciencedaily.com/releases/2012/04/120402162546.htm suggests The proposed mechanism is decreased tissue sensitivity (and specifically immune cells) to cortisol. This is presumably a result of prolonged periods of high cortisol due to chronic stress. Cortisol would normally dampen down inflammation; if cortisol isn't having an effect, inflammation runs amok. The link between the two studies mentioned as leading to this conclusion and the conclusion doesn't sound very strong to me. But, if our problem is inflammation, and if the inflammation is a result of cortisol insensitivity, that would surely be an easy thing to prove? I'm not too sure how cortisol insensitivity can be responsible for everything from cardiac disease, to asthma, to autoimmune diseases to heightened cold symptoms as well as ME, but only one or some of those diseases in any one person. And why not everyone who has endured, for example, a civil war or a prolonged series of earthquakes develops ME. Is this when we wave our hands around vaguely and say 'genetics'?
Genes Brain Behav. 2007 Mar;6(2):167-76. Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome. Link to abstract here (With apologies to all of you who have lived through this or at least know this already.) This 2007 study with authors including Unger, Vernon and Reeves seemed to find that people with CFS shared polymorphisms of the glucocorticoid receptor gene (NR3C1). I haven't read the full text but even in the abstract the HPA axis gets a mention. There were only 40 participants with CFS. I wonder how supported this finding has been in subsequent genetic investigations.
I’ve had psoriasis since I was 18 and any type of stress, physical, mental, or emotional, will likely trigger a flare up if the stressor isn’t short lived. Since getting ME/CFS my psoriasis has gotten worse in every respect and it’s easier to trigger a flare up when there is stress. Stress is a well known trigger of flare ups in autoimmune disorders. So if this is real then I think your op is totally plausible.
Dr Bansal was researching glucocorticoid receptor resistance which suggested cortisol resistance. Research has not been published, so i don' t know if it is a null finding @alex3619 was interested in it. Dr Bansal retires from NHS this year. It was explained in the LIME conference in Sweden 2014, which was posted on another thread. Prolonged fight or flight is not good for anyone, epigenetic changes have been suggested which modulate gut, ( including triggering leaky gut and inflammatory response to LPS) vitamin absorption, blood pressure, glucose metabolism.If the body cannot keep up supply to meet demand then it will impact onto endocrine system , and other systems. I think the argument is that since this response is literally survival instinct that long term exposure to stress rewires things to cope with a dangerous environment- a kind of evolutionary reboot. But our bodies can' t distinguish between stressors so a combination of physical and emotional stress may be more detrimental. I did a flow chart when my daughter was being bullied to try and understand the effects.i will try and dig it out and you can all tell me where i have gone wrong! Gene expression ( and the ability to switch this off and on ) may be the difference between developing one illness over another when all other variables are factored in. Cortisol as far as i know ( i am not scientific) does not have the " nested control" mechanism of other hormones/ compounds, with multiple feedback loops, which may explain why it has such potential to wreak havoc.
True, but surely we would see a massive rise in the incidence of ME in places where the citizens have all undergone a substantial stress if emotional stress was a major factor in ME. True, but my children and I did not have significant emotional stress when we developed ME and the illness that seemed to precipitate the ME was not very severe. This 2017 review paper by two Australian endocrinologists https://www.ncbi.nlm.nih.gov/books/NBK279099/ is a bit odd in places and completely wrong in some others. However, it does cover the stress causation theory in great detail with lots of references. I do not understand how the assumption of low cortisol in people with ME prevails when the studies show the majority of PwME have cortisol levels in normal range.
I think there are many roads into this illness, which is part of the reason it is so hard to crack. My daughter's base cortisol is low, so perhaps a subset.
The only thing that I'm aware of that is more or less clear (I think) is the connection between stress and mast cells. Not saying that mast cells have something to do with mecfs, but they might. They likely have something to do with eczema and many other skin conditions though. E.g.: Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor. or Mast cells and inflammation But the more interesting thing is that at least in this study, they found that CRF (which is released under stress) does not really lead to MC secretion on it's own, but potentiates it: I think it plays quite well into what we see in the real world. Healthy people can handle enormous amounts of stress and have little to no problems, but people who have some kind of susceptibility may react negatively to it.
Yep, just as people who are non anaphylaxis can eat nuts and non diabetics can eat sugar etc. The mechanism of the disease is not the trigger and the triggers are not the cause.
Even minor distress puts you at risk of chronic disease https://www.medicalnewstoday.com/articles/322464.php
So if you diagnose people wrongly with anxiety or depression then they get a later diagnosis of MS or Cancer does that mean the first claim was wrong?
Flow diagrams - pre ME and scientific paper referencing - screenshots as pdf too large I was trying to understand the symptoms as they manifest themselves. I know they are pretty basic - helped me at the time> I find graphics easier to get my head around
The study is here: https://www.jpsychores.com/article/S0022-3999(18)30047-3/fulltext#back-bb0150 I don't even know how to explain this part: That's a lot of messing about to mangle the data into a mess! (They could have used the income data to measure socio-economic position). Their method makes somebody getting unemployment benefits have the same socio-economic position as somebody earning a full wage. Nevermind assuming (wrongly) that the categories have the same socio-economic status differences. If you assume that an income of £75 per week is the same category as say, £1,000 per week, and that moving from one to the other does not affect your socio-economic status (or amount of stress and anxiety), I don't really know what to say.