I've heard it phrased "Stress wrecks the body in strange ways." It is one of the best aphorisms I've been given. A physiologist friend told me this years ago when I was remarking how it seems like psychological stress seems to cause every subsystem of the body to freak out, yet there's no obvious connection between these things - why should the brain, which is evolutionarily "late", affect such deep subsystems?
This paper offers a clue into just such a connection. Immuno-psychiatry might be the next big thing.
This is also the reason why a lock-down against a virus is not always the best option for healthy people. A lock-down causes stress and this weakens the immune system.
Personally I think it is obvious why the connection between stress and 'subsystems' is there.
Stress puts the body into survival mode. Heavy breathing is an example. But when the stress holds on for too long it exhausts your body causing all kinds of trouble. The most extreme example is a burnout.
That is one aspect of a lockdown. But there are others and they are different for each person.
In the Netherlands it was estimated that a lockdown would save 150000 life years but would cost 650000. This takes into account a huge number of factors. For example health, but also job safety, happiness, and so on.
A lockdown causes stress for a lot of people. It seems you are not one of them.
Yes I'm not denying that it causes people stress. Just putting my thoughts in.
I think because I'm not stressed about it I'm definitely in a position of privilege. There are people who could not work during lockdowns - and I can completely understand why such people would be stressed. Not being able to make a living, and not knowing what's to come.
I think modern-day type of sustained, prolonged stress is just not something we've experienced much of prior to x,000 years ago, so there are simply no failure modes evolved yet.
A lot of the bad aspects of the stress response come from prolonged periods of not being able to do anything about it. If your village is raided, and you escape unharmed, you will be very stressed for a short period of time, but generally return to your baseline quickly after that. That's normal. That's what "stress" is for.
The modern world has the ability to stress you out over things you can do nothing about (or at least, not very directly and quickly), for long periods of time. Sit down and watch three hours a day for a week of whichever news channel pisses you off the most if you want to see. Some of you reading this already do that, so you may not even notice how pointlessly stressed that makes you because that's how you live. It also has a bunch of other humans who find it advantageous to stress you out that way and bend a lot of time and effort to the task of continually stressing you out, because they prefer that you not be able to carefully think about things but that you react less thoughtfully. You spend more money that way, among other effects.
Past life would spike the stress levels more often, sure, but it generally lacks the low-grade continual stress you can't do anything about. The exceptions that leap to mind (sieges! famine!) would generally be exactly that, exceptions. And in those cases... I'm sure the continual stress of sieges and famines wouldn't be good for them, either!
You don't actually have to be in conditions of siege or famine for them to be stressful. They merely have to be a threat. And what would a common person (i.e. peasant) have been able to do about that threat?
If your village is raided and you escape harm (quite the assumption), why would you generally return to "baseline"? What if the raiders took all your food and you can't feed your family? What if your family was murdered or raped? What if your village was destroyed and you're now a vagrant?
You are making the cognitive mistake of seeing the exceptions as the default, because the exceptions are what come to mind.
As I said, when constant persistent stress was occurring, I'm sure it wasn't any better for them than for us. But those were the exceptions. History writes about the famines and the sieges precisely because they're the interesting exceptions. Most people, most of the time, were not in a siege or a famine or under any particular threat from a neighbor.
Today, millions upon millions experience this mid-level persistent stress all the time, for decades. In the 21st century first world, it is the norm, rather than the exception. I don't think that's how it used to be. It especially didn't used to be that way when the danger of famine or siege is as low as it is now, making the stress response even more mal-adaptive.
I guess we just have different reads on history. I don't think it's a mistake to view hard times as the default for most of history in most places. They were of course not constant and there are accounts of exceptionally hard times. But I think the background level of hardship for the common person throughout the world >1000 years ago would probably drive most people currently living in the modern first-world to catatonia or suicide.
That's an oversimplification. The threat of war was not an everyday occurrence and really only became a thing when tribes evolved into nations and countries. Burnout is an example of the types of stress that are not like anything experienced in those thousands of years prior.
The threat of violence in the form of intra-tribal and inter-tribal violence was commonplace, even though nation states weren't a thing. I can't imagine that being less stressful than today where we have very close to zero chance of being murdered.
Hence the "predators and inclement weather". You can't imagine experiencing "burnout" with regards to incessant cold and rain preventing your tribe from effectively hunting/foraging? Or a pack of starving wolves harassing your camp at night for weeks?
Take this a step further and consider vaccine mandates.
However flawed or not the antivaxxer's reasoning, imagine the stress of having to choose between yours and your children's livelihood or being forced to inject a substance you consider risky into yours or your child's body.
The bulk of that fear comes from ignorance about how vaccines work, and there's enough reputable sources to get educated for free, learn how they have worked in the past, and make an informed decision.
It's more stressful to be sick two weeks and struggling to breathe because you got COVID, and I'm saying that as an asthmatic who is not scared of mild difficulty to breathe.
There is no sensible posture to rationalize antivaxing, but every country has a percent of the population who hesitates about vaccination, and a percent that not only refuses it, but stubbornly refuses to practice hygienic measures. This should be taken into account when designing future health programs.
I dont know if the brain should be considered so late. These subsystem would never have existed if not for the command center helping them to survive and evolve, even if you argue there was a soup of mono cellular machines for very very long.
People who have more background than me: What does this have to do with memory and recall of immune responses?
So they infected a mouse, monitored the mouse’s neurons to see which ones are active during inflammation, then waited a while, then hit those neurons again and observed inflammation even though there’s no disease the second time.
If they hit the “same” neurons in a mouse that never had the disease in its lifetime, wouldn’t they observe inflammation without memory? (I don’t think they tried it)
The prevailing knowledge about the immune system says that immune responses are stored in T-cell reservoirs, not in the brain, and that immune cells are produced autonomously from the bone marrow in response to immune cell activity in the body. The brain doesn't inform or control this system.
This research seems to indicate that not only are specific immune responses stored in some area of the brain, the brain can trigger such a response by itself.
That’s a really good question. I didn’t read the full paper yet, but I think one of the important discoveries here is that there’s a direct causal relationship from brain->immune system in the first place that would allow them to trigger specific responses.
It’s also probably hard to target those same specific neurons without first triggering the immune response since that’s part of their method for finding them.
"Side effect" is perhaps not the right term, since the effect loops back into the processes; evidence for that is that we are talking about consciousness.
Do we know this is true? Could the loop back also be an illusion? From a cursory glance it seems like "free will" is massively exaggerated. However, the belief of free will seems to be healthy.
There is no largely accepted obvious place where free will emerges from, while at the same time superdeterminism is not proven as you say.
So it's fair for some to say that physics as we know it doesn't allow free will, while at the same time it's fair for others to say that obviously they have free will thus it must exist.
free will is very inefficient in a power/performance sense: most decisions are made by your subconsciousness and your free will rational self will just accept the outcome if it is barely plausible. you have to focus to even be aware that it's happening.
I’ll get downvoted for this pseudoscience, but I sometimes wonder if free will is the feeling of the infinite number of universes splitting and your “choice” is merely which branch you ended up in…
this gives a tiny sliver of credibility to stories about people focusing really hard for really long on imagining tumors being eaten by their immune system and this actually happening. used to sound like total crap, now... just crap? it'd be amazing if it wasn't.
Neurons and the immune system are deeply linked. They found that anxiety is caused by a weak immune system and strengthening the immune system will lower anxiety.
They have been injecting viruses into animal brains and doing gain of function edits on viruses for understanding fear responses in mammals and making them more infectious to mice and apes to study their brains after viral infection. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568141/
>The use of viral vector technology to deliver short hairpin RNAs (shRNAs) to cells of the nervous system of many model organisms has been widely utilized by neuroscientists to study the influence of genes on behavior. However, there have been numerous reports that delivering shRNAs to the nervous system can lead to neurotoxicity. Here we report the results of a series of experiments where adeno-associated viruses (AAV), that were engineered to express shRNAs designed to target known plasticity associated genes (i.e. Arc, Egr1 and GluN2A) or control shRNAs that were designed not to target any rat gene product for depletion, were delivered to the rat basal and lateral nuclei of the amygdala (BLA), and auditory Pavlovian fear conditioning was examined.
If anyone doubts the effects of infection on the brain and just says its just a mouse experiment consider the effect of mental effects of untreated syphilis. Its been observed throughout history. They only do experiments on rodents but many have been "humanized" like giving them genetic diseases like making rats that are genetically prone to depression, obesity or having fatty liver disease. They have even used human stem cells to transplant human livers into rats. https://www.upmcphysicianresources.com/news/060220-mini-live...
I think more technically it is nocebo effects which cause the (bad) immune response, whereas the placebo effect cancels or at least ameliorates it.
Paul Garner has described how worry about covid helped to maintain his long-covid / ME/CFS symptoms, and he was finally able to recover after addressing those fears:
I managed to fully recover from ME/CFS myself 20 years ago with a similar route (with no symptoms since). In my case I don't think there was any significant worry about the illness itself, it was more pre-existing life stressors that I had to deal with, with the viral infection being the final straw for my body.
I think that some people have post viral mental disorders. Or just general mental problems after going through anything out of the ordinary with their body. After going through Thyroid Cancer I generally don't give two thoughts about much of anything, while people at work are 25 years old and getting boosters for Covid. Some kind of mental thing going on here.
One thing I also found out during this pandemic is people generally don't get sick which was surprising to me since I have 2 kids and have generally been sick with a cold every 2 to 3 months for a decade. Maybe that's why Covid wasn't that bad for me? Although it did put me on my ass for 2 days.
Placebo is such an interesting phenomenon. I had a certain physical pain difficult to describe that I could’ve sworn to have felt, but after addressing my perspective I’ve no longer had any such symptoms. Not sure if related, but I still don’t understand it.
I find it a rather disturbing phenomenon, to be honest. Governments, scientists and media insist that we place enormous faith in the outputs of medical trials and studies. Anyone who expresses doubt about these is ostracised and forced to comply regardess. Yet every single one of them has to control for this entirely mysterious, inexplicable force that magically heals people with no actual medicine. This effect is so real, large and standard that it's mandated by law to take it into account yet we understand basically nothing about it (often even what the placebo was chosen to be is opaque), it's barely researched and the total lack of ability to explain it doesn't seem to bother anyone. Least of all regulators, who are meant to ensure the effect size of trials are correctly interpreted.
It feels like there's this enormous, sophisticated scientific edifice that can draw pictures of proteins and explain how they interact, and in the centre of it all is a giant rotating question mark that everyone by convention ignores and pretends isn't there.
It's not like they don't try to figure it out. But as you said:
>> "This effect is so real, large and standard that it's mandated by law to take it into account yet we understand basically nothing about it"
What would you prefer doctors do? Not use life-saving and life-improving treatments that are proven more effective than placebo after rigorous trials just because they don't understand it 100%?
The problem is we currently tend to ignore certain biases in our process which are known to introduce errors. Once it becomes a recommended medical practice that medical professionals use, medical opinion often trumps common sense and patients have trouble defending themselves even when they, personally, are certain this is harming them.
Doctors will outright suggest you are mentally ill and need to see a therapist if your life is on the line, you aren't satisfied with their course of treatment and you question what they are doing and/or express concerns that this could kill you. Once they more or less declare you crazy for questioning them, you lose even more control over your body, your health, your life and your right to actively make decisions for yourself.
There is definitely room for improvement in our current process.
That western medicine is often full of itself, deeply [insert -ism or -phobia] in practice, and frequently misguided is all very true and reasonable criticism. The person I replied to was essentially writing off the entire foundation of western medicine because doctors and medical science people don't always fully understand why things work.
It would be like someone writing off Newtonian physics before quantum mechanics was a thing because a lot more of the how wasn't yet understood. The practice of medicine has moved past the "if she floats, she's made of wood, and that means she's a witch" phase even if it still sees anyone other than cishet white dudes as witches.
I don't know. But how can we really claim things are "proven" or the trials are "rigorous" when they literally assume some sort of magic in their fundamental design? I mean we should at the very least dial down our certainty in medical claims until scientists can satisfactorily explain why they think new age woo/homeopathy/etc is beyond the pale neanderthal stupidity, up until the moment it's relabelled "placebo" when suddenly it can work.
I mean we're in an environment where the US President is forcing an entire nation to take an experimental medical treatment on the back of (failed!) trials, simply because politician's faith in "science" and the medical establishment is 100% unshakeable. Largely because scientists themselves hardly seem to admit to the true levels of uncertainty in their own work (replication crisis etc). There's a huge mismatch between people's perception of study rigor and "sometimes people think themselves better lol magic innit", which is basically the state of our understanding of the placebo effect.
(don't want to put words in GP's mouth, this is my interpretation of it, and my experience)
I do skateboarding and had multiple ankle sprains. What happens every single time is that the wound heals, physiotherapy proceeds and strengthens the whole joint system, and then I'm left with an ankle that is still in pain when it should not physically be anymore since it has fully recovered.
That is, until I literally "decide" the remaining pain is a construct of my mind, and then the pain vanishes overnight, and the ankle that I felt brittle and was scared to use to its full extend suddenly feels as strong and stable as ever, if not more.
In a nutshell, the idea that there's a straightforward causal link between something being physically broken in your body and you feeling pain is simply wrong. Sometimes people feel pain in various body parts without any detectable physical changes and sometimes classical training injuries, like herniated spinal disks, can be found by medical imaging without the person feeling any pain at all. Also the common advice to rest until the pain subsides is often - but no always - wrong; there are plenty of anecdotes of people with completely fucked up knees or ankles or back starting heavy powerlifting program and suddenly healing from their injuries or at least learning to use their body in such a way that the injuries don't bother them anymore.
I dont know about rapidly resuming the activity that caused the injury, but I totally agree that stopping all activity to exclusively rest and recover is terrible. You have to try to walk a bit at the very least.
I participated in a chronic pain study where I personally learned that there are times, much more often than not, that one should not second-guess their joint that is having a flare-up and continue to walk a similar amount each day. I can't overstate how empowering it is to not be in a thought loop on a case by case basis and trust the learned system.
Increased blood flow, released endorphins, usage of muscle, flexing of connective tissues and operation of joints often addresses the issue (if it is not an acute injury that really does need our body's regenerative abilities). We evolved to walk.
Physical activity -- muscle movement -- also increases the flow of interstitial fluid back to the circulatory system. This is how the body "takes out the trash" which is essential to the healing process.
I have a serious medical condition. I sometimes go for a short walk when I feel awful because I know from long experience that doing so frequently makes me feel better and I've gotten good at telling when I feel awful in a way that will likely be helped by taking a walk.
This connects the dots even further! I had a time where I went on a walk and thought it would be an extremely short one. After I thought I had been hitting the wall and I was sure I was making it worse, my joint started feeling much better. I extended the walk and returned feeling like the flare-up I had been experiencing before the walk had rapidly dissipated. That was a defining learning moment for me.
Placebos generally aren't sugar pills, unless there is sugar in the medication itself (which I don't think is generally the case). They are designed to be impossible to tell apart from the active medication.
The pain-killing effect has nothing to do with sugar.
Not to say Wikipedia is infallible. I'm sure it's not. Just checking how clueless I am and the internet suggests my understanding is "common knowledge."
Perhaps you can share more of your knowledge about what placebo pills typically contain and enlighten us? (Citations welcome should you choose to share.)
Actually, I did some searching and it seems that most RCTs don't actually list the contents of the placebo pill. I found this article which describes the problem:
Thank you. Very enlightening and happily agrees with both your statements (that they usually aren't sugar pills) and mine (that placebos themselves may have medical impact).
> For example, in the COVID-19 vaccine developed by the University of Oxford, the control group receives a meningitis and septicaemia vaccine as a placebo.
> The benefit of using an actual vaccine as the placebo control is that it will cause a similar reaction at the site of the injection as the COVID-19 vaccine, such as muscle pain and soreness. This prevents patients from knowing whether they are getting the placebo or the real treatment.
It'll be interesting to see if this validates the bizarre claims of the Wim Hof method. I'm skeptical, but the evidence _seems_ to suggest a lot of conscious control over some autonomic functions.
The wikipedia article on wim hof where they quoted the study seems a lot more believable:
" . . . forceful respiration results in increased sympathetic innervation and glucose consumption in intercostal muscle, generating heat that dissipates to lung tissue and warms circulating blood in the pulmonary capillaries. Our results provide compelling evidence for the primacy of the brain (CNS) rather than the body (peripheral mechanisms) in mediating the Iceman's [Wim Hof's] responses to cold exposure.[28]"
By hyperventillating you are just flexing your intercostal muscle and that's warming your body. If you sat there flexing your quads or your core over and over you would probably get a similar sensation.
That's in response to cold. He has also been tested for effects on immune response:
"It was shown that this individual was able to voluntarily activate the sympathetic nervous system through a self-developed method involving meditation, exposure to cold, and breathing techniques. This resulted in increased catecholamine and cortisol release and a remarkably mild innate immune response during experimental endotoxemia compared with more than 100 subjects who previously underwent experimental endotoxemia."
Given the brain’s regulatory role in virtually every aspect of homeostasis, I’m surprised that folks are surprised that by mental exercises autonomous functions can be influenced if not controlled. Wim Hof is interesting, but any Hindu can tell you that yogis have been performing similar feats for millennia.
I think its worth nothing that the Wim Hof method also includes both cold exposure and breath holds, both of which I believe are physiologically linked to the immune response.
Though the article does seem to suggest that focusing your thoughts in a particular way could be involved as well. Pretty cool!
It seems the immune response of Wim Hof method occurs as a result of intentionally creating an adrenaline response in the body. Apparently other breathing techniques do this prior to Wim Hof (Tummo breathing). Andrew Huberman, a neuroscientist at Stanford talks about the science of this https://youtu.be/JPX8g8ibKFc?t=2161 (at that timestamp he talks specifically about adrenaline breathing)
Yes, but any type of memory decline linked to immunity decline would be interesting, as memory performance is known to decline in older adults, who also have a decline in immune function.
What’s really interesting, thymus involution becomes more or less clinically relevant just around the time cognitive performance begins to decline.
Fair enough. We should be cautious but meanwhile almost every gene found in mice so far has been found in a closely related form in humans. Of the approximately 4,000 genes that have been studied, less than 10 are found in humans but not in mice.
This paper offers a clue into just such a connection. Immuno-psychiatry might be the next big thing.