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Psychological factors and IBS

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
This paper claims to support causation being psychological, but I tend to think the reverse in at least many cases - gut dysbiosis causing psychological disturbances, notably anxiety and depression. This can occur through the tryptophan pathway switching to producing kynurenine, for example.

Again, I don't have time to read the paper, and can't access the full text, but would be interested in what others think. I know that @alex3619 is interested in this issue. I suspect that @Jonathan Edwards will take issue with the claim "stress affects the immune system."

(Edited to add link!)
 
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A.B.

Senior Member
Messages
3,780
These articles are usually predictable: "we found a correlation between psychological factors and disease, and therefore the psychological factors are causing the disease". Alternative explanations or concrete evidence will be absent.
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
These articles are usually predictable: "we found a correlation between psychological factors and disease, and therefore the psychological factors are causing the disease". Alternative explanations or concrete evidence will be absent.

On the nail A.B.
 

user9876

Senior Member
Messages
4,556
These articles are usually predictable: "we found a correlation between psychological factors and disease, and therefore the psychological factors are causing the disease". Alternative explanations or concrete evidence will be absent.


There is often an additional problem. They way they assess psychological factors is through a questionnaire but the question answers could sometimes follow from disability rather than from psychological problems.

So in any work like this they should carefully justify that questions and answers are independent from the effects of the other problems they are talking about. However, they normally don't look at the actual questions but hide behind a 'scale' name.
 

Hutan

Senior Member
Messages
1,099
Location
New Zealand
Some of you might be interested in this radio item from Australia's Radio National on the gut problems causing psychiatric problems.

http://www.abc.net.au/radio/programitem/pez4DqMobD?play=true

There's a transcript too.
Cutting edge science is discovering that to an extraordinary degree, not only physical health, but brain and mental health is dictated by what goes on in the gut.
...
The microbiome is the collection of bacteria in the GI tract, and for years we always thought that our thoughts and our feelings affect our GI tract, so we might get stomach aches, we might get diarrhoea when we are nervous. But over the past 20 years or so we now understand that the gut can affect brain function. The amount of bacteria that we harbour in our GI tract is massive. There are more cells, more bacterial cells in our gut than there is in our entire body, three to four pounds of total weight of bacteria, and what we are finding is that this collection of bacteria, this microbiome if you will, has tremendous neurophysiological effects on mood and behaviour and appetite.
...
It was renowned Greek physician Hippocrates who said that 'all disease begins in the gut'. Today we take a closer look at how scientists are starting to see the gut as our second brain.
...
We know that the gut, for example, makes more than 90% of very important neurotransmitters, like the happy chemical serotonin that is the reason people take antidepressants, to raise that chemical. More than 90% of that is made in the gut. The gut plays a huge role in detoxifying the body, keeping the brain in a healthy state. The gut manufactures various vitamins that are critically important for the brain.
...
So when we see changes in the gut bacteria resulting in inflammation, driving down available serotonin, it gives us a strong connection in terms of our understanding as to why depression is now looked upon as representing an inflammatory disease.
...
One of the most studied is the action of a chemical that lives in the gut, it's called LPS, it stands for lipopolysaccharide. When it gets through the gut wall, when the gut wall isn't functioning appropriately, in other words when the bacteria are imbalanced or when we've consumed certain foods that challenge the gut lining or take certain medications that challenge the gut lining, then this LPS gets out and stimulates certain white blood cells that then go on to create the chemical mediators of inflammation called cytokines. So this is a process by which changes in the gut through this chemical LPS get out of the gut into the systemic circulation and amp up inflammation.
...
James Greenblatt is unusual, being a psychiatrist who treats the gut for mental health issues, but he says that the scepticism in his field is decreasing.
...
There is not a robust level of research indicating the effectiveness of, for example, probiotics. But I think the exciting part for me as a clinician, as an individual dealing with patients all the time, and that is that I think the door is open to a whole new area that we never conceptualised before. Now I think I can at least say that I for one as a brain specialist am very hopeful that there are new opportunities to treat patients, but I think that it needs to be done in a very measured, careful, safe way.
 

A.B.

Senior Member
Messages
3,780
Another problem here is that people were assessed during the outbreak, not before. This means that people had already come into contact with the pathogens.

Maybe the anxiety was simply the symptoms of exposure, and the IBS the long term consequences? There is certainly no shortage of patients who say that changes in gut health result in surprising changes in mental and emotional health.

Another explanation along the same line is that the people with anxiety already had some gut problems, which got worse due to the outbreak.

Just to add some alternative explanations to the discussion.
 

Hutan

Senior Member
Messages
1,099
Location
New Zealand
While you are at Radio National, there's another item on gut flora that is interesting.
http://www.abc.net.au/radionational/programs/bodysphere/your-microbial-body/6722600#transcript

Amanda Smith: Well Rob, you and I are 99.99% identical in our DNA, as are all human beings. How similar are you and I as far as our microbes go?

Rob Knight: We might only be about 10% the same in terms of our dominant microbial species. So, there's this tremendous similarity at the level of our human DNA but whereas our gut microbes, one person to the next, are very different.
...
And the healthy microbes helped to reduce the inflammatory response. COPD, a big part of that is inflammation. So these results, where you can cause a positive response in a disease that's in the lungs by manipulating the gut microbiome, are promising. And we hope to follow this up and maybe a therapy will come out of it down the track.
...
Tim Spector: It's going to soon revolutionise how we look at food and diet. Because in comparison we've been spending billions of dollars on genetic research (and I'm a geneticist by training so I'm not trying to knock it deliberately, and we've found hundreds of genes), but if you give me a blind test of a fat person and a thin person and you give me their microbes or their DNA, the DNA will be pretty much useless in predicting which one is which. Whereas I'll get the fat person and thin person right 95% of the time.

Amanda Smith: With their microbes.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
There is certainly no shortage of patients who say that changes in gut health result in surprising changes in mental and emotional health.

Myself included. Been anxious for most of my life. Changed my diet in my late 50s, added some supplements, gut function improved dramatically, as did sleep, and anxiety decreased significantly. Whenever my gut gets messed up again, mood, sleep, skin, sinuses and other things take a turn for the worse.
 

jimells

Senior Member
Messages
2,009
Location
northern Maine
ABC said:
So when we see changes in the gut bacteria resulting in inflammation, driving down available serotonin, it gives us a strong connection in terms of our understanding as to why depression is now looked upon as representing an inflammatory disease.

Is there evidence for any of this? As I understand it, there is no evidence for the "Serotonin DeficiencyTheory" of depression and that it is actually a marketing story to sell drugs that barely work better than placebos. So that kinda blows a hole in the bacteria -> inflammation -> serotonin deficiency -> depression theory.

I have no opinion or knowledge of bacteria causing/ not causing depression, but here they are building on a foundation of beach sand.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Is there evidence for any of this? As I understand it, there is no evidence for the "Serotonin DeficiencyTheory" of depression and that it is actually a marketing story to sell drugs that barely work better than placebos. So that kinda blows a hole in the bacteria -> inflammation -> serotonin deficiency -> depression theory.

I have no opinion or knowledge of bacteria causing/ not causing depression, but here they are building on a foundation of beach sand.

Serotonin may be a red herring, as other things are affected too. See this quote from this paper:
Up-regulation of TRP – KYN metabolism limits availability of TRP as a substrate for minor pathway of TRP metabolism, i.e, biosynthesis of serotonin and other methoxyindoles: N-acetyl serotonin and melatonin [4].

TRP = tryptophan and KYN = kynurenine.

Although the source paper for that quote is about people with HCV receiving interferon-alpha, the source of the quoted info (reference 4 cited above) is more generally about the serotonin-kynurenine hypothesis of depression.

The first paper also states that indoleamine 2,3-dioxygenase (IDO) is even more strongly activated by interferon-gamma, which was found by Hornig and Lipkin to be high in the first 3 years of ME/CFS. It also says that IDO is
the rate-limiting enzyme of TRP conversion into kynurenine.

So more interferon = more IDO = more kynurenine = possibly an increase in depression risk.


EDIT

It was interest in this issue that led me to start this poll, but it hasn't supported my hypothesis! Maybe poorly worded/controlled/not enough participants.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
there is no evidence for the "Serotonin DeficiencyTheory" of depression and that it is actually a marketing story to sell drugs that barely work better than placebos
Actually its very clear that replacing serotonin does not remove depression. Pharmacologists knew this in the 80s. It is very much a marketing ploy.

The first part of the issue is that Selective SRIs are NOT selective by biochemical criteria. That's marketing hype. What is the case is they were designed to be a bit more selective than the previous generation of drugs.

When I was learning the pharmacology of SSRIs, circa 2001, nearly all of which I have forgotten, it was pointed out they knew that the serotonin reuptake was not why these drugs could work. It restores serotonin levels in hours, but depression takes weeks to resolve. Other candidate drugs, which were highly selective under biochemical criteria, failed. What we did not know is whether or not the serotonin might have been important in conjunction with a second mechanism induced by the drugs.

The more biochemically selective the drug, the less it worked. These more effective serotonin restoring drugs never made it to market.

This is quite aside from the growing evidence that for most patients, most of the time, SSRIs are a placebo. Its a minority of patients with very severe depression who respond best, and massively increase the effect size in studies. Its a subgroup.

This does not mean, however, that other mechanisms are not at work. It just means that serotonin, by itself, will not resolve depression. Other things, other pathways, may have an effect though, the science is just not evolved enough.