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Researchers Find Further Evidence That Schizophrenia Is Connected to Our Guts (discovermagazine.com)
274 points by prostoalex 4 months ago | hide | past | web | favorite | 169 comments

There is good reason to be skeptical of the claims in the article. This twitter thread [1] is a good, articulate criticism of the issues around the paper.

To quote a segment from the series of tweets by the author, Kevin Mitchell (a neurogeneticist from Trinity College, Dublin)[2] :

"1. A supposed mechanism in search of a phenomenon... (What is the microbiome supposed to explain here?)

2. No actual mechanism.

3. No actual findings. Just lots of exploratory blips, unconstrained by prior hypotheses, uncorrected for multiple tests, and unreplicated.

4. Massive hype.

Just because the genetics of complex disorders is complex and just because the neuroscience of the highest functions of the human mind is complex, doesn't mean we need to go looking for new kinds of biology to explain them"

[1] https://threadreaderapp.com/thread/1095012297200844800.html

[2] https://www.kjmitchell.com/

[edit: formatting]

Shameless ad-hominem here, since there's not much to grab onto in that guy's argument:

Be careful who you believe. This grumpy genetic determinist is clearly out of touch with an entire field of emerging research about the gut-brain axis.

Apparently this guy you're quoting is also skeptical of epigenetic inheritance. (http://www.germlineexposures.org/blog/no-convincing-evidence...)

Why should I listen to him again?

He's hung up on finding a singular "actual mechanism" in a complex, nonlinear system? I know almost nothing about this guy but I suspect he's another a drug company biologist, desperately holding onto shattered dreams of genetic determinism.

So, if you actually read the 3-4 blog articles [1,2,3,4,5] on epigenetics that he's written, I don't interpret them as him suggesting epigenetic changes do not occur.

Rather, I think he is challenging the notion that epigenetic inheritance is the driver of / underlies behaviour change in mammals.

I disagree with your assertion that he is skeptical of epigenetic inheritance. I think he's skeptical that epigenetic inheritance can drive multi-generational neuro / psychiatric behaviour change, which is a far more nuanced position to take.

For instance, had you made the effort of actually checking his blog, [5] is a response to the article you linked / cited:

To quote him:

"So, in case I have come across as merely unpleasantly grumpy, let me spell out my general grounds for being skeptical of the claims of TGEI in mammals."

And further, in the context of behaviours and neuro disorders, and their inheritance in humans.

That's what he is commenting about. Not epigenetic inheritance in general. In as much as you didn't actually check his writings and painted his position with such a broad brush and value judgements, then yes. I would agree this was shameless and an ad-hominem attack indeed.

Now, I don't know this guy. But his arguments, especially the lots of different ways in which biologists mis-interpret and mis-apply statistics rings true. His arguments are cogent, and his analysis reasonable and conservative. Which, in science (the conservative interpretation) is an excellent thing, IMO. So yes, I do choose to consider his opinion carefully.

I think, in all this hype and buzz-wordy social media noise that appears to be driving everything including research and politics, it's important to identify and defend the voices that are saying, slow down, let's not read too much into these things yet; let's not get carried away.

Jill Escher, whose article you linked to, is a lawyer by training. This guy is a neuro-biologist and a professor at Trinity College, Dublin. Who do you think has more credibility here?

This suggests to me that you didn't even look the people you were citing up, or who you were criticising. Surely, you can do better?

[1] http://www.wiringthebrain.com/2013/01/the-trouble-with-epige...

[2] http://www.wiringthebrain.com/2013/01/the-trouble-with-epige...

[3] http://www.wiringthebrain.com/2014/04/the-trouble-with-epige...

[4] http://www.wiringthebrain.com/2018/05/grandmas-trauma-critic...

[5] http://www.wiringthebrain.com/2018/07/calibrating-scientific...

[Edit: added excerpt and replaced "crap" with "noise"]

I don't think a Twitter thread is an adequate response to an academic paper. Twitter is the equivalent of the homeless man yelling at the bus stop.

Eh, homeless people are occasionally right and a little less hysterical. Twitter is the equivalent of a small dog yapping at the homeless man yelling at a bus stop.

Various polls over the last few years show Twitter is the 2nd or 3rd most popular social media site for news. Right behind The FB.

This is as good as it's probably going to get from here on out.

I think the most obvious question is “does schizophrenia cause an abnormal gut microbiome or does an abnormal gut microbiome causes schizophrenia?”

My bet is it’s the former, not the later.

Then you need to explain how the fecal transplants triggered similar symptoms.

Maybe schizophrenia is not a sickness, merely a epi-genetic adaption to bad circumstances. Have a little civil war? Turn yourself into a twitching little zombie and walk it off?

So if you transport the message, you get a universal reaction.

Definitely. Eating patterns, sleep and many other things change. Even medications like lithium. What's lithium do to bacteria? My anxiety makes eating hard sometimes so i eat bad foods just to get calories in.

It is sad, because there is certainly a link, it’s not just the direct one that all academia is jumping to conclusions.

You pretty much nailed all those studies. Those type of hard to characterize, very complex, and poorly understood diseases, are the only candidates that you will see a “microbiome can cause/cure it” type of paper.

At the end of the day, they see a mouse, bearing a set of mutations that is not even close to mimic the disease population, adopt some new behaviors, and then they miraculously cured everything.

On top of that, VC have started to invest massively in that field, even starting their own company. On one side, I hope this will bring some much needed robustness to the current lack of rigor. On the flip side, since the biotech VC model is to IPO whithin 5 years, I doubt they will do better.

Or, more likely, they are both effects of the same root cause...

Or is there some third factor that causes both such as stress, high levels of innate immunity activation, etc.

Or it could be a feedback loop with multiple possible starting points.

I don't understand how these could possibly be mutually exclusive.

The professors behind this work are well known and credible.

Which is good but also not enough.

It’s a different league than a twitter thread.

It's reasonable for a twitter thread to point out methodological issues in a study even without prior credibility.

If the original research were in a twitter thread rather than a publication, it would be unreasonable to consider it seriously.

Where we'll known and credible.

Then they reversed causality for some wild theories.

Also worth mentioning that Science Advances is a relatively new open-access journal, which is distinct from and significantly lower status than the journal Science. Although I can't speak to the reputation of Science Advances, Nature has a very similar sister journal, Scientific Reports, that is distinctly mediocre.

Aside: I think this whole "status thing" is hurting scientific progress. You want to work in academia? Better publish x papers a year in a "reputable journal". This attitude is what leads to quantity over quality approach, and results in all the p-hacking and overhyping. Negative results are likely to go unpublished.

Here reputable = discriminating

And these low-reputation journals are poorly discriminating. Status here has a reason.

>Just because the genetics of complex disorders is complex and just because the neuroscience of the highest functions of the human mind is complex, doesn't mean we need to go looking for new kinds of biology to explain them

After decades of looking for brain abnormalities and finding none it really is time to look elsewhere.

Not to mention that "new kinds of biology" are becoming hugely credible. There's a massive body of work emerging about the gut-brain connection.

This Mitchell guy is in denial.

I did my thesis on one possible cause of this illness 20+ years ago and then never looked at it again.

After just reading up on the possible causes of schizophrenia it seems many more discoveries have been made which has only resulted in more confusion and we're basically nowhere near having a clue.

One of the most important points that rarely come up in these discussions is that schizophrenia is not one illness but a bunch of different ones grouped together that we haven't figured out how to differentiate. You can find several patients that share very few symptoms.


> One of the most important points that rarely come up in these discussions is that schizophrenia is not one illness but a bunch of different ones grouped together that we haven't figured out how to differentiate. You can find several patients that share very few symptoms.


I remember meeting someone at an alumni networking event who worked with mentally ill people, including schizophrenics. He explained to me that a lot of his patients had extreme sleep apnea, and their CPAPs were turned up much higher than a typical sleep apnea patient.

His theory was that some of his patients were mentally ill due to their sleep disorder.

My grandfather started having hallucinations (auditory mostly - i.e. hearing voices and carrying on conversations) and showing signs of paranoia (like thinking his house had been broken into when it clearly had not, thinking people were spying on him). We were afraid it was dementia or Alzheimers.

He went to multiple doctors to verify the cause, but wasn't getting anywhere - didn't seem to really be either thing, but exhibited similar symptoms. He was eventually diagnosed by a super competent neurologist with extreme sleep deprivation due to sleep apnea.

When tested it was determined that his sleep apnea was waking him nearly once a minute, but he wasn't becoming fully conscious and therefore wasn't aware he was constantly waking up. He was never entering deep sleep at all. It was more like moving out of dozing into almost-awake and then back again rapidly all night long. He knew he was tired, but had no memory of really restless sleep.

He started using a CPAP and the symptoms started declining immediately. He was back to himself within a couple of weeks. It was really astonishing - I had never heard of anything like this - and of course it was an enormous relief for everyone in my family.

Yeah that was happening to me. I was being woken up a little less than half that (average of 27 times an hour). I was constantly seeing and hearing things, but they were too indistinct for it to be called something like "hearing voices".

It was more that I really often saw a flicker of motion in the corner of my vision or thought I heard someone mumble or say something that I didn't quite catch. These hallucinations were easy enough to rationalize away - maybe the people near me just took a breath weirdly and I thought it was a word, or a bird flew nearby or something.

I didn't realise any of the above were symptoms until I I noticed they weren't happening to me any more a few years after I had started treatment and hadn't happened in quite some time.

I can easily see myself ending up like your grandfather after a few more years of living with severe sleep deprivation. Ironically I got treatment when seeking help for insomnia (because it took me a ridiculous time to fall asleep and could basically only do it when I was completely exhausted)

And a high intensity cpap was inducing a sleep disorder?

Couldn’t he easily test that by having the patients reduce the intensity?

I interpreted GP's comment differently:

Unusually high CPAP intensity indicates unusually severe sleep apnea, suggesting a connection between sleep disorders and mental disorders.

Reflecting on the impact sleep has on my mental health, that makes intuitive sense.

The opposite: The high intensity CPAP was treating the disorder.

I was rather scared at the time, as my CPAP was almost up to the level of the patients. (I got surgery shortly afterwards.)

But I will admit this: There was one time, prior to my CPAP, where I had trouble knowing if a memory came from a dream or real life. Makes me wonder if some mental disorders are just about having difficulty differentiating between dream state and awake.

I think that’s the case for pretty much all of the major psychological diagnoses. Depression, autism, attention deficit disorder. They’re as much a disease as fever or a rash are diseases.

I think we’re still maybe a step or two beyond the theory of humours in how much we understand the brain and what effects it and how it effects us. We’ll look back at how we’re treating a lot of those symptoms today as barbaric in a few decades, I think.

Most if not all brain illnesses may be due to high oxidative stress/neurotoxicity and brain inflammation. A weak/imbalanced gut microbiome may be incapable of dealing with that, which is why we may be seeing the "connection" between the two (brain illness = weak gut).

To me the most interesting and convincing part is that fecal transplants from schizophrenic patients to mice changed the mice's behavior in ways that are similar to schizophrenia, as well as changes in glutamate levels. This shows some kind of causal link more than just correlation.

I feel like all the comments are ignoring this part of the blog post

from a twitter thread [1] critiquing the paper, by a neurogeneticist [2]:

" And we can test them on a whole range of behaviours, without correction for multiple tests, without a hypothesis of which should show an effect, and again without a replication sample In this case, the ones getting a SCZ fecal transplant showed greater activity, but less anxiety and less "depressive" behaviours. Why? Who cares? You can spin these kinds of findings any way you want. We all love a good story."

Please read the cited thread.

/disclaimer: I am not a neurologist / neurobiologist. My training was in genetics & molecular biology, and I've since moved out of active research / life sciences. But bad statistics and gross over-interpretation bothers me immensely; folks read such breathless reports & then start doing all kinds of harmful stuff because it's been proven! But it's not. It may be a hypothesis (and this report may not even qualify as that). And cruel as it is, we still don't understand nearly enough about so many things in biology to be able to address these disorders.

[1] https://threadreaderapp.com/thread/1095012297200844800.html

[2] https://www.kjmitchell.com/

I'll take one well-designed and peer-reviewed study over 100 random Twitter threads.

What about twitter threads from well-respected researchers in the field? What about a poorly-designed study (for the reasons pointed out in the thread)?

I don't see any reason to believe that guy is well respected outside of the pharmaceutical industry.

I don't know if the Twitter thread is from a well-respected researcher, or whether their criticisms of the study are valid. That's my point.

It sounds like you're not the target audience of either the paper or the twitter thread.

Again, you make it sound like these are somehow equivalent. Why even have peer-reviewed journals in the age of Twitter?

Because this is how science has always been done, it's just visible on twitter now. Someone submits a paper to be published. A few scientists look it over and check for basic correctness. Then the paper is published and people read it. If the paper is interesting, they start talking about it. They use the breakroom, email, twitter, facebook, science journals, backs of envelopes, and anything else that's convenient. This conversation about a paper is a critical part of the community absorbing a new piece of evidence. From these conversations, subsequent experiments are planned and published and science keeps moving forwards. These conversations are not as formal as a journal publication, but they are much more formal and structured than laypeople usually realize. Comments are worded in particular ways, and only certain kinds of objections make sense. Proving things about nature is an excruciating task that requires an enormous level of care and evidence.

the point of the twitter thread is that it is not a well designed study.

Yeah, but I'm not a scientist in this field, so I have zero idea of whether the Twitter thread itself has any credibility. So I'll ignore it.

One problem, my cousin has schizophrenia and often seems plenty confident and happy. The only time I’ve seen him otherwise is during a migraine, which made sense.

It really feels like recently someone developed a new method to characterize the microbiome, and now people are correlating that meassure with everything like the probability that people eat green m&ms (no correlation) that they eat blue m&ms (no correlation) yellow m&ms (no correlation) have scitzophrenia (slight correlation!). And publish what ever hits a notisable p-value. But it all leaves me skeptical of everything to do with the microbiome.

We all know green m&ms cause acne.

But it is a problem. Lots of people publishing just to publish (a consequence of how academia is laid out), and then sensationalist media who doesn't understand what's actually being said, or why to be skeptical (or maybe they do, and just don't care) , takes over and runs with it.

But isn’t this how science works? We discover a new way to measure something, and then we start evaluating its usefulness as a measure. When and where we find interesting relationships, report that out, and then start looking for causes. Perhaps the new ruler is broken, or perhaps we learn something we didn’t know before. Regardless, I see reports such as this one as interim findings necessary to either justify or pursue additional funding.

VC and SV entrepreneurship is pretty much the same game. That’s why you have the “Uber for X” syndrome. Sometimes it sticks, sometimes it doesn’t. We are all human search functions reporting back to the hive mind.

It’s not exactly how science is supposed to work. New measurement technology should result more from a pull than a push. That is, the scientists studying mental diseases probably want a better/more specific way to measure brain activity, because most of their mechanistic hypotheses revolve around brain function. In this case, they’ve been told that there’s a new way to measure gut microbe populations, and the cool part is the technique produces so much data from a single sample. Somethings gotta correlate!

Now I don’t actually think the gut microbiome is just an automatic p-hacker - most studies are measuring pretty standard aggregate measurements of “diversity”, not just finding one class of the billions of bacteria that happens to correlate, so I’d agree with the OP that the question is more one of causality. And since a fecal transplant from an ill mouse caused signs of illness in an otherwise healthy mouse, then there’s reason to follow up.

I think it's a chicken-egg problem, so we are likely to not find agreement.

Sure, sometimes you have a hypothesis and you go searching for a way to measure something.

Other times, you find a new way of looking at things, or you come across some new fascinating data. This helps you generate hypotheses for which you need to design new studies, not least of which is to ensure that the new measuring tool is measuring what you think it is.

I definitely agree with the sentiment that the product of research such as this shouldn't be policy or a change in world view. It should be hypothesis generation and new testing.

that is the opposite of how science is supposed to work. Using the method described you will statistically always find false correlations in data sets. This is because you can find patterns in any set of data.

You have to start with a hypothesis and then come up with the measures and expected outcomes based on it. Then you design the experiment to determine if the hypothesis is false.

absolutely. I think what's happening is the "let's see what sticks" approach. I'll throw every possible symptom and try to draw correlations in every possible way. We can always come up with a hypothesis later.

Which, while its an effective way to do science when we don't know what we don't know, has to be interpreted with lots of caveats & caution, and should only be considered to be the 1st step in a long, deliberate investigative process. And that doesn't seem to be the case, particularly in how pop-sci articles communicate the results.

Yep. it s a trendy subject. I would wait 3 years before taking any of them seriously

> and now people are correlating that meassure with everything

You consider the fecal transplants to be mere correlation?

People underestimate the industry involvement with this hype. Microbiome drows lots of water.

Most of these types of correlations turn out to be nothing. Don't get your hopes up.

If a study shows A and B are correlated, it could be any of:

1. A causes B. 2. B causes A. 3. They are both caused by a third factor C. 4. Random chance. 5. Bad experimental design. Science is hard. 6. Fraud. 7. Probably other things I can't think of right now.

As far as I know, the gut microbiome is most directly affected by what you eat. Do schizophrenics have different eating habits than non-schizophrenics?

Would you believe that peoples' appetites could be affected by their microbiome?

Anyhow, it's perfectly reasonable that people suffering Schizoaffective disorders might have different interactions with common foods that are considered tolerable by "most people".

I have no trouble at all accepting this. Our gut is loaded with neurons. To imagine this, consider that when you are feeling happy, they said its like "butterflies in the stomach". Now consider a situation when someone cannot feel this due to fucked up gut. That on situations when you are supposed to feel happy, you are attacked by anxiety instead, which are also a distinct sensation in the gut. Your life will become a nightmare. I've been there myself, thankfully my gut is good now.

On the flip side, there are people out there with super gut, that feel happy no matter what life throws at them. Just a dose of optimism to lighten up the mood.

> I have no trouble at all accepting this

That's not how science works. If something is proven and reproducible via the scientific method, it must work(used to make verifiable predictions) whether you accept it or not.

Let's never forget https://en.wikipedia.org/wiki/Diederik_Stapel . His M.O. was to fabricate results that would be easy for his peers to accept.

And if we take into account all the dangerous pseudo-scientific hype around the gut(leaky gut, cleansings, etc) we should be twice as careful.

Understood and agreed. This is more apt a reminder in a thread about schizophrenia too.

I predict that over the next decade or so we're going to find that almost every medical issue has some microbiome component, just like pretty much everything has some level of genetic risk factor. The human body is too interconnected to expect anything else. I just don't want people to throw out the baby with the microbiome-quackery bathwater that's coming as well.

absolutely. I would hope people don't now start doing fecal transplants for treating depression, or Alzheimers, or schizophrenia. These results, interesting though they may be, are not a cure; they may not even be diagnostic.

But clearly, diet, the gut microbiome, the immune system, at the very least, are linked, and linked tightly. So it would not be surprising at all, that there's a microbiome component. But we don't know what it is; how it affects the underlying disorder, and how to approach it for treatment as of now.

And as you alluded to with "genetic risk factor"; its well possible that though there is a component of the microbiome involved in the disease; it may not be significant enough to act as a vector for treatment. Or that it is just a comorbidity. We just don't know!

>I would hope people don't now start doing fecal transplants for treating depression, or Alzheimers, or schizophrenia.

Why not? That would be a fast way to find out if it works.

Because if they keep eating a poor diet that encourages an unhealthy biome, they're going to defeat the point of a fecal transplant.

And you don't know what downsides fecal transplants may have. There's clear preliminary evidence that gut microbiomes can drive obesity. Imagine giving someone who is not obese / diabetic a fecal transplant to treat depression.

That doesn't work (the treating depression part), but suddenly, this person becomes more susceptible to obesity / develops diabetes.

These things must not be rushed into!

I'm not sure if you're alluding to this, but it's supposedly already happened.


Damn. Thanks for the link. I was just speculating..

I don't think the authors are drawing a casual effect here; in effect, this is scientific anecdata: hey, we tried this and this happened. We think you should know.

I think it's great they published the result, even if the n=1.

Assuming this is due to the fecal transplant, it just goes to show, we are messing with a major functional system in the body. And we should tread very very carefully. Scary..

The most direct connection between Schizophrenia and the gut is the neurotransmitter Serotonin. Which plays a central role in the mechanics of the disease as well as in the bowels. This is by the way also the reason why consumption of psychedelics (which are mostly binding to the serotonin 2a receptor) will usually cause bowel irritations from flatulences to nausea.

We basically have a huge bioreactor in our stomach. Surely it is possible to introduce some gene into the collection of bacteria there that could cause the production of metabolites that are destabilizing to mental health.

Would be curious to see if some kind of gut bacteria intervention could ameliorate symptoms.

From what I understand about Schizophrenia, I would expect limited potential here at best. The schizophrenic brain is structurally different: for instance the hippocampus of schizophrenic people is disorganized, and schizophrenic people have less gray matter than neurotypical people.

It's plausible that to some degree these changes could be reversed to some degree long term of they're the result of a tonic stress from the gut biome, and it's also possible that acute schizophrenic episodes could be ameliorated if it turns out they're triggered by the gut, but it's highly unlikely that replacing the gut biome of a schizophrenic person would give you a neurotypical person.

The other thing about schizophrenia is that people usually develop the disorder in their late teens or early 20s with an acute episode. If there is indeed a link to gut bacteria, and if you could identify pre-symptomatic, high-risk individuals, I would imagine this could create a very compelling vector for preventative treatment.

Even if correlation doesn’t imply causation maybe there’s that link in this case as they have done a controlled experiment. They seem to just have stopped short of claiming that schizophrenia is caused by a bacterial gut infection. I wonder why they didn’t claim that?

Probably because it's only a comorbidity. We seem to want easy answers to all these question but the reality is that humans are complex organisms. Having one issue (i.e. an infection) without another (i.e. some specific genetic corruption) will not result in the individual developing a disease however the combination of 2 or more factors results in the development of a disease.

People with schizophrenia get put on anti-psychotic medication. One of the side-effects is significant weight gain. It's likely that this weight gain is affecting gut-microbiome.

It's nice to see they're being a bit cautious.

Are there any really, really extra-sane people to serve as fecal donors?

In the future I'm guessing fecal donors could become a thing like plasma donors are - as in it could become a paid "side hustle?"

These sane, rational folk should surely flock to that opportunity!

One nice experiment showed the big difference biota make may be choline absorption. https://medium.com/@russjj/choline-is-it-the-key-to-modern-i...

I second this. Great book. One of my faves.

I know this is dangerous close to the nature /nurture no-man's land but my own pet theory is that schizophrenia is a loop deformation. Every habitat swings, as in the circumstances are unstable going from a plenty of food to no food, zero disease to plague, nil predation to over predation. All this happens in evolutionary short time, meaning it should be invisible to the blind and deaf process that stupidly adapts to whatever is not worst enough for the circumstances. I found that schizophrenia beeing one of these specializations to a swinging habitat, as a theory, had a lot of explanationary power. Unfortunately it has sad implications. If you are adapted to circumstances, it makes only sence to prolong these circumstances. If the habitat swings back, the dormant version will lie in wait looking for epi genetic triggers, that allow this loop adaption to pre-emptive return and attempt to spread displacing other loop adaption. I do not know if a discussion on this can remain civilised.

Anyone interested in a theory of schizophrenia that actually explains the logic behind these behavior patterns would do well to learn about Bateson's "double bind" formulation.

Dr. Stanislav Grof's essay "Mind, Nature and Consciousness" provides a very lucid introduction to this theory (http://www.stanislavgrof.com/wp-content/uploads/pdf/Gregory_...):

"The basic idea of Gregory Bateson's theory of schizophrenia is that this disorder basically represents a breakdown of metacommunication [messages about messages, indicating how the communication should be understood, i.e. a wink to indicate that this is a joke, /s for sarcasm, etc]. Psychogenetically, this problem can than be traced to a specific disturbance in the communication between the mother and the future schizophrenic which involves what he called a "double bind.”

The basic characteristics of this situation are the following:

1. The child is in a relationship of vital dependency, where it is critical to identify correctly the communication from the mother.

2. He or she is receiving from the mother messages which are contradictory, since the qualifying metacommunication denies the verbal content or is otherwise incompatible with it.

3. The child does not have the opportunity to ask questions to clarify the communication.

4. The child cannot leave the field. Under these circumstances, he or she is forced to distort his or her perception of the outer world and of the inner feelings, and is incapable to develop meta-communicational skills.

Gregory's favorite example was a situation in which a mother, annoyed by a child who is active and noisy, tries to get rid of him by saying: "Darling, it is very late and you must be terribly tired; mommy will put you to bed. You know I mean well for you." The message misrepresents the truth about the matter. It says "you are tired and need to sleep" instead of "I really need some space for myself." Messages and situations of this type force the child to deny or disregard his or her inner clues and accept what the mother is saying.

Metacommunication is extremely important in human communication and individuals who do not master it tend to have great interpersonal difficulties. Metacommunicationally inept persons who are incapable to read subtle signals, understand jokes, and decode hidden meanings become easily victims and scapegoats of their peers. There has been much discussion, whether this mechanism is sufficient to explain serious psychopathology encountered in schizophrenic patients. Gregory Bateson himself believed that much of schizophrenic symptomatology can be understood as a total breakdown of metacommunication."

This theory is total bunk. It is widely considered to be discredited and a great example of fanciful psychological theory with no scientific backing.

I mean, if this theory was true, you would expect to find schizophrenic families--after all, they all had the same mother. It also doesn't line up with the timing of onset at all.

You provide absolutely no evidence of this theory being widely discredited. The reality is it seems to be very difficult to test empirically. The most comprehensive survey I have found to date is here: http://www.goertzel.org/dynapsyc/1997/Koopmans.html

"I mean, if this theory was true, you would expect to find schizophrenic families--after all, they all had the same mother."

First of all, maladaptive social behavior of the kind that is labeled as "schizophrenia" (or other so-called mental illnesses e.g. "bipolar", "depression") does tend to cluster in families. This is why doctors screen for things like "family history of depression."

Secondly, there are major differences in siblings' roles and how they are treated, despite having the same mother. The birth order concept is the most obvious version of this. There is another concept of the "identified patient" which explains how in some cases one family member plays the role of the "sick one" as a way to maintain stability of the family unit as a whole.

"It also doesn't line up with the timing of onset at all."

I don't see how this theory conflicts with whatever timing of onset you are referring to. Perhaps you can clarify or provide citations for what appears to be a very strongly held opinion.

> does tend to cluster in families.

Yes but not necessarily at the sibling level, which is what you'd expect if this was a problem caused by bad mothers.

Also, you would predict that siblings should be highly correlated regardless of their genes if it was "mothering" but instead what you find is this (from the study you cited):

Monozygotic Twins 44.3

Offspring two schizophrenic parents 36.6

Dizygotic Twins 12.1

Siblings 7.3

Offspring one schizophrenic parent 9.4

Half-siblings 2.9

So a half-sibling raised with the same parenting is barely correlated on schizophrenia, but a twin has a 44 percent correlation. That puts the schizophrenogenic mother theory 100% off the reservation in my book. Reasoning past that damning fact is just wishful thinking.

> I don't see how this theory conflicts with whatever

The average age of onset is 18 in men and 25 in women. If this disordered thinking style is created in say 6 year olds, it seems odd that it takes 12-20 years to cause a problem.

Anyhow theories are a dime a dozen, and the burden of proof is on those proposing the theory to prove it, and that has failed rather spectacularly in this case.




Separated twins show high concordance for schizophrenia (why would this be if it is due to parenting?) https://www.ncbi.nlm.nih.gov/pubmed/2285075

Another study: https://journals.sagepub.com/doi/pdf/10.1177/140349481039656...

The important bit: It was concluded that genetic factors are important in the transmission of schizophrenia, whereas there was no evidence for environmental influences in the rearing family.

Do you have a citation for wide discreditation? Wikipedia is more circumspect

> Bateson's double bind theory was never followed up by research into whether family systems imposing systematic double binds might be a cause of schizophrenia. This complex theory has been only partly tested, and there are gaps in the current psychological and experimental evidence required to establish causation [citation?]. The current understanding of schizophrenia emphasizes the robust scientific evidence for a genetic predisposition to the disorder, with psychosocial stressors, including dysfunctional family interaction patterns, as secondary causative factors in some instances.


(Which makes me wonder: if the predisposition is genetic, why don't we have schizophrenic families? After all, they have the same genes!)

I think it's highly unlikely that there is any meaningful causal link between a particular parenting style and Schizophrenia.

We currently have a very robust physiological understanding of the disorder, and the symptomatology is linked to observable structural changes in the brains of Schizophrenic individuals.

As with many psychological disorders, there appears to be a stress component: i.e. individuals may be more or less predisposed to the disorder, and therefore some individuals will only ever experience symptoms if triggered by a high level of stress, while for others it's unavoidable.

So in some cases, yes it's possible that a problematic family life was the stressor that pushed them over the edge to develop full-blown Schizophrenia, but that person might have equally been effected by being mugged at gunpoint, or going through prolonged sleep deprivation during basic training in the military.

The causal mechanism is almost certainly an interaction with Cortisol or other stress hormones, or some other well understood biological pathway. It's outdated pseudoscience at this point to take seriously the idea that Schizophrenia is the result of mixed messages during childhood.

> We currently have a very robust physiological understanding of the disorder, and the symptomatology is linked to observable structural changes in the brains of Schizophrenic individuals.

While I agree overall with your point, I think your wording emphasizes a common but mistaken view that psychological experience can't induce physiological changes in the brain. This is obviously false.

Yeah I absolutely agree that there is a feedback loop by which neural activity actually shapes physiology. But there’s also a degree to which psychological disorders are contributed to by errant thought patters, verses being the result of a functional problem with the brain as an organ. For example, with some forms of depression cognitive behavioral therapy (changing your thought patterns about certain things) can be very effective, while in the case of serious bipolar disorder, medication may be the only way to mitigate manic episodes.

For lack of a better analogy, there’s a degree to which different disorders are the result of a software problem or a hardware problem, and all the evidence points to Schitzophrenia as being firmly toward that hardware end of the spectrum.

I again agree with everything you've said, but to tie this all back to the article and the microbiome, while the body does have discrete, specialised organs, we have to recognise that they are leaky abstractions.

Microbiota could influence psychology and thus physiology, or it could directly affect physiology and thus psychology. The fact fecal transplants triggered schizophrenic behaviours in mice shows there's some direct connection here that needs explanation.

> Microbiota could influence psychology and thus physiology, or it could directly affect physiology and thus psychology.

On maybe it's neither and also both. Personally I think Physiology vs Psychology is the wrong terminology to use: Psychology's domain is the mind which is a somewhat abstract concept, and usually refers to things in terms of thoughts and emotions. Our "psychology" is an emergent property of our physiology, but to me it seems like the wrong abstraction to use as a reference point when speaking about the pathology of something like Schizophrenia.

Rather, what I think we're more concretely talking about is the division between nervous system structure (physiology), and activity (which includes, but is broader than psychology).

To me, saying the physiology affects the physiology implies the wrong interpretation: i.e. it would be inaccurate to say that the gut bacteria made rat feel certain emotions or have certain thoughts, and those led to long term structural damage. However, it might very well be the case that the gut biome causes a neural activity pattern which leads to long-term pathological adaptations in nervous system structure.

If I had to guess, there's probably not a one-way causal relationship, but these systems likely feed back on each-other in a way which results in the symptomatology we describe as Schizophrenia.

> The fact fecal transplants triggered schizophrenic behaviours in mice

What are schizophrenic behviours in mice?

They discuss this in the article and the linked study which did the transplants. You're best off consulting those.

That was an interesting read, thanks!

In HN you will find a very hostile audience towards the idea that an _inner world_ exists at all. This is unfortunate, when I denied my inner world I lived only half of what I experienced, and I insisted that all my problems could be resolved with pills and external stimulus. This leads to a barren emotional life and a distinct sensation of being stuck in the same place, which eventually leads to depression.

The problem is which of the billion _Inner worlds_ ideas to accept. I mean, isn't religion/spirituality good enough for you? Why should we pollute science with such stuff?

If you have an opinion or idea that isn't reproducible, verifiable or testable and the only thing you can do is "accept" it based on how good it sounds to your ears then it doesn't belong in science.

So please, leave that stuff out of science, it's our last barricade.

'such stuff', subjective and irrational as it is, was the foundation of all science last time i looked.

You checked in the wrong place then.

Why are you spreading such nonsense?

i know some people who think math is nonsense. turns out that they don't know any. So i must ask if its nonsense to infer that you have no experience with families and people other than your own circle, no experience with subtle factors of any kind?

if so, you'd be quite vulnerable the next time someone offers you a double bind.

Math is science, so no one cares if they don't believe in it. The above is not.

All of your remaining assumptions are wrong, so no reason to even bother.

This is fascinating. I've wrestled with anxiety and depression my whole life. It seems quite intuitive to me that there is a gut link. I frequently experience "butterflies' in my stomach. I frequently have gas, too. I wonder if I could participate in a study? I'd be happy to.

As someone with both IBS and anxiety, this is slightly scary

I have suspected IBS and suspected Borderline (diagnosed MDD and Anxiety) and I swear to god my stomach health is related to my mental health. Correlated, perhaps, but there's definitely some sort of relation based on my experience.

ps; probiotic yogurt makes me very happy

Same with the yogurt; I'm actually planning to start taking probiotic supplements to simplify that aspect, as well as a fiber source called phylum husk.

Sorry to hear about the Borderline. Just remember that mental health diagnoses are less rigid than traditional medical diagnoses. You've heard of mind over matter; mind over mind is even more effective.

I take a fibre powder I make myself, but there are premixed versions:

Rice bran, oat bran, psyllium husk, ground linseed, and slippery elm powder.

Typically equal proportions, but it varies depending on how much of what I’ve got left when it goes in to the mixing bowl.

I also regularly buy not continuously take a priobiotic and / or Greek style unsweetened yogurt.

Lots of Vitamin D. I also need to supplement essential fatty acids or my skin tears at the edges of my nails.

Plus running and lifting heavy things. Also dogs. My dogs are well trained, they know our routines, and they make me laugh out load a lot!

Take a look at VSL #3, a heavy duty probiotic.

Also, check out partially hydrolyzed guar gum which has some promise for IBS. It is a prebiotic fiber (feeds your beneficial bacteria) and also like psyllium husk does not produce a lot of gas which is bad for IBS.

Hope you feel better! :)

This might sound crazy but if u are able to fast for 2-14 days straight it will help so much . It seems to have had a very long term effects .

First try doing OMAD and see how u react . Basically fast for 23 hours and eat for one hour . If u think you can handle doing that for a week. do it a few days straight

Fasting for 14 days does sound crazy. I remember hearing of a diet that simulated fasting though. Anyone has experience with that?

Borderline is rough. I feel for you!

You might find this interesting:


Interview w/ a doctor focused on the links between gut, autoimmune, and mental health.

It actually points to a possible solution: If you get your IBS under control, your anxiety may improve.

You might look up the term somatopsychic (assuming you don't already know it) and start thinking of mental health issues as probably at least partly rooted in physical health issues.

I'd be curious to know if anyone can anecdotally confirm a slightly different, but similar connection to IBS: chronic pain.

I have read that IBS is implicated in fibromyalgia, including shoulder pain, but I am interested in the reverse causal direction: can a painful shoulder injury cause IBS?

If nerves and the gut are tightly connected, it seems plausible that pain receptors would also be implicated in both directions. (Of course, going back to the link to the central nervous system, your brain doesn't have pain receptors, but it is connected to every nerve in your body.)

I don't have chronic pain personally, but anecdotally (from friends, not just myself), there tend to be general correlations between anxiety, depression, food intolerances, allergies, chronic pain, migraines, chronic tiredness, eczema, etc., which of course makes intuitive sense. It's not surprising that mental health has an effect on these other things; it's more surprising that the opposite could be true. It really just seems like everything is much more connected than we'd like to think

The idea that our minds and bodies are deeply connected is frowned upon despite clear evidence:



...I'll blame Cartesian though and the idea of free will for this.

It really just seems like everything is much more connected than we'd like to think

I think you're right. So much so that my doctor actually suggested prescribing SSRIs for the IBS, even in a patient (such as myself) having no signs of clinical depression. I didn't take the prescription, so I couldn't say if it would have helped in my case, but I went home and read a study that SSRIs have been shown to alleviate IBS. Pretty interesting.

I can't anecdotally confirm that, but could speculatively postulate a possible explanation for such a phenomen, assuming you are interested.

I am in fact rather interested! A few years back, I went through a lot of physical therapy for a shoulder injury, and within a month or two, I had a year and a half long bout of IBS and leg cramps. Ultimately I controlled the condition (somewhat) with diet, but I can't help but think the real problem was simply that my pain was the original trigger.

Since the problem has only mostly subsided, I'd be thankful for any ideas about just what was going on.

Cartilage has no blood vessels. It gets all its nutrients from osmosis. Wastes are removed the same way.

Osmosis is a less efficient means than direct blood supply, so joints probably tend to accumulate wastes firsts if they aren't all being removed from the body for some reason. Anecdotally, cartilage and nervous system tissues are the last things to heal. Everything else has to improve first.

Also, some infections, like strep, are known to settle in the joints. The shoulder is one of the larger joints and has a fair amount of cartilage and similar tissues.

So, you injure a major joint and old infection hiding out in the joint gets released into the blood stream. This impacts the entire body.

But the gut is where you find 70 to 80 percent of immune cells in the body. My hypothesis is that it is because food is the single largest threat we deal with on a daily basis.

So you have what amounts to an internal toxic spill and it stresses the gut because that's the largest concentration of cleanup crews. Dealing with this crisis taxes the entire immune system, but you are most aware of impact on the gut because that's where the vast majority of your immune function is found.

That's a very interesting theory. I had assumed that the immune-system hadn't been implicated in my case (all the immune-system bloodwork came back normal), but now you have me wondering just a bit, so thanks for sharing.

Your body goes to enormous lengths to normalize your blood because you rapidly die if your blood leaves a fairly narrow pH range. So it will strip your bones of calcium, leaving you with osteoporosis, to keep your blood as close to normal as possible.

I am skeptical about the value of blood tests. It seems to me that by the time a blood test shows a problem, things have to be pretty bad. I think reliance on blood tests probably misses a lot.

/More speculative postulating

Edit: I was almost certainly barking up the wrong tree here: calcium levels have nothing to do with how much your joints pop. :-)

Hmm, well that part about calcium is quite interesting, at least in my case. I say this because right around the time I started getting leg cramps, my joints started popping like crazy.

My working hypothesis was always that the tight muscles were pulling on the joints, causing them to pop more easily. But maybe now I was actually being slightly deprived of calcium? I say slightly because the calcium blood levels were normal.

Eat more yogurt and relax. You're going to be okay.

This is one of the sweetest comments I've ever read on hacker news

It’s misguided and incentive. Gut diseases aren’t cured by yogurt.

For many yogurt would be a bad thing to digest. For others it works perfectly. Depends on what bacteria you have/need. Too complex for a one liner.

Ymmv, but I've found it helpful.

Even if well-intended, I think it's condescending.

One improvement to my life is assuming positive intent. If there is a way I can interpret someone's comment in a positive light, I do so. I'd rather occasionally seem like a fool who didn't realize he was being insulted than hurt somebody by falsely accusing them of being mean.

As a bonus, I am insulted a lot less ;)

Fwiw I didn't take it as condescending

Telling people with anxiety or depression to "relax" or "just be happy" is pretty insulting.

A person with asthma or a broken leg is usually not told to just breathe or just go for a walk.

Okay I definitely agree with you in situations where people are being invalidating.

Tone is hard to read on the internet. Personally I read that comment as reassuring rather than invalidating. (Of course it wasn't directed at me). I get anxiety quite regularly and have battled depression since age 10 after experiencing something very traumatic. When someone manages to successfully reassure me, I'll take it. It can help break me out of my digging.

I got severe IBS, depression and anxiety after gastroenteritis. By changing my diet I solved the three problems (among others).

There is something called gut-brain axis that does not seem to be mentioned here. It is a relatively new discovery. But this finding, gut-schzophrenia, is not something surprising at all. Gut-brain axis is such an important part of our biology that it's probably connected to everything in one sense or another. Schzophrenia, depression, our psychological health, you name it.

C4 gene led to a greater risk of developing schizophrenia https://www.economist.com/science-and-technology/2016/01/30/...

I'm genuinely curious what yogurt might do to someone with schizophrenia. I also wonder what their dairy consumption looks like and their diet to see if there's relations.

There's also genetic relations with schizophrenia. I've always wondered if these had to do with nature or nurture. Often studies simply say they check a person's mental health background. Is it really genetic? Perhaps it could also be what gets taught and passed down to us or the home we live in.

Perhaps the mental illnesses that our society experiences is nothing more than poorly regulated drinking water, mold in the walls, a bad diet, Mom's spaghetti, or spices that don't agree with us.

I find this research very interesting. The bacteria change could be a side effect of something but since the bacteria is atypical, it leads to a very interesting question: How did it get there?

What foods carry this bacteria? Does this bacteria kill other healthy bacteria? Does it serve a purpose?

I'm not a biology specialist, but I would love to know if nutrition is related.

I'm guessing it's an interaction between your genetics and how you react to food. Just like how some people are more prone to diabetes or don't every really get fat and don't manage their diets consciously.

Are you implying that people who dont really get fat, who dont manage their diet consciously, are more prone to diabetes? I never heard of this...

I think they were giving the example that given the same diet, one person might develop diabetes while another would maintain a healthy weight due to predisposing genetic factors.

But actually it does seem to be the case that the ability to put on fat is in some ways protective against diabetes. In other words, people that easily store calories as fat don't have the metabolic problems associated with diabetes, since their body is able to effectively store any extra calories they take in. Diabetes develops in individuals who are not effective at converting excess sugar in their blood stream into fat, so instead they suffer metabolic damage. That's not to say that they don't put on fat, but if you see someone who has an enormous amount of excess fat, they are likely to have a much higher threshold before they develop the disease.

good to know, since i can.not put fat no matter how hard i tried (admittedly not very hard).

I'm schizotypal (schizophrenia lite, essentially). I eat tons of Greek yogurt. Dairy is my favorite food group. I really struggle with thought disorder, and when I eat well, I feel a lot less crazy and mentally disorganized. Definitely eat better than the stereotypical American.

So Schizophrinia should be curable by clearing the gut bacteria? Sounds like something we already would have known if it was the case. Don’t strong antibiotics clear the gut? And isn’t the microbiome changed within days of traveling to a new country?

A gut cleared of bacteria is not a healthy one. The microbes are necessary, and the genetic makeup and relative populations of microbes have some powerful consequences for a person's health. Fecal transplants are an effective treatment for a number of things.

...”if those things are gut related illnesses “

Finished your sentence.

You're right, of course it is limited to gut-related things.

Probably not. I elaborated more in another comment, but Schizophrenia is characterized by long-term structural changes to the brain. Clearing the gut bacteria is unlikely to reverse those changes.

But as a preventative measure it could be interesting. If this theory is correct, there could be people out there who never developed schizophrenia because they did a course of Cipro at the right time and nuked their dysfunctional gut biome. We would have no way of knowing.

And mainstream people still think the idea of high fructose corn syrup, gluten, etc. affecting mental capability is just people being OCD...

One thing that is fascinating is that the Danes are supposedly the happiest people on earth. I wonder what their microbiomes are?

This is only tangentially related but has anyone here read the book 'The Fiber Menace', and if so, what are your thoughts?

Is there a link between gut bacteria and diet?

Is there a link between gut bacteria and diet?

Yes. There are lots of articles (based on studies) on this. For example:


For those who haven't already read this book Alanna Collen's Book is a good start on the significance of microbes for human health [1] https://www.amazon.com/10-Human-Microbes-Health-Happiness/dp...

The next possible conclusion can be that antibiotics cause schizophrenia.

They can depending on the class. Fluoroquinolones yes. Penicillins not likely.

What makes you say that?

Apparently there's research. I did a search, low and behold this is known.

There is no credible evidence that antibiotics "cause schizophrenia". On the contrary, there are trials to use antibiotics to treat it.


Here's a case of Levofloxacin inducing acute psychosis. For someone at risk of developing chronic psychosis, acute psychosis can trigger an avalanche.

There are other cases in which this has happened, and it's to the point where the FDA has administered a warning:


Schizotypal disorders are dynamic and non-deterministic. So I agree with your skepticism around the word "cause". But in this case, I think it would be unwise for someone with a history of schizotypal symptoms to use fluoroquinolones.

I fear the incoming online information war between everyone and anti-antibioxxers.

Anti-antibioxxers? Have you been reading quackwatch on the wayback machine again?

Wasn't schizophrenia fairly recently attributed to an off-by-one error in the brain while deleting old brain cells, taking more than necessary, essentially a natural algorithm gone wrong?

It’s a long-studied and complicated condition, I don’t think we’re anywhere near having such a concise explanation of its causes yet (etiology). There are many competing theories each with different levels of support. There is also reason to believe that schizophrenia is multiple disorders that are currently lumped into the same category because we’re not good at differentiating them (similar to the way different types of cancer are lumped under the label “cancer”).

Trust the science, but don’t trust the science reporting.

I was talking about this (pruning of synapses):


This study pointed out 90+ days of taking minocycline/doxycycline during adolescence "had a significantly reduced risk of a subsequent psychotic disorder diagnosis than did those receiving other antibiotics." - from their 10-years sample of electronic records.

I had a suspicion that as you say "schizophrenia" might be an umbrella term for many distinct diseases with similar symptoms.

But, is that a symptom of schizophrenia? Does it cause other symptoms? Is it caused by other symptoms? Is it common to all forms of schizophrenia?

For me as a computer scientist with interest in medicine (using Deep Learning to beat humans in detecting diseases), this was a cool finding pointing to a possible algorithmic reason behind schizophrenia. Now it might be just a small part of the puzzle, intertwined with other mechanisms we don't understand with overly complex interactions, not mentioning it likely misses other, completely different diagnoses sharing the same label.

So yes, your questions are perfectly adequate, though for me personally that finding is exciting, as I can potentially apply supercomputing on that problem.

The comments on the website are a good laugh.

I don't see how that could be possible, unless it is a transmissable disease that infects the brain.

And if it's not the microbiome it's probably something to do with quantum entanglement.

I knew it! The CIA really has been fiddling with my guts when I sleep! Just wait until the aliens in my teeth hear about this.

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