Woah. Does this imply that a fecal microbiome transplant, from a source with zero-to-low levels of Ruminococcus gnavus, would be sufficient to cure schizophrenia?
It would have to be the right protocol—heavy antibiotic pretreatment, moviprep for good measure, anaerobically prepared donor material etc.—but yes. There may be alternatives to FMT, though; a bacteriophage active against gnavus, maybe some things that are antagonistic to its growth or the activity of the AADC enzyme. I suspect that hydrocinnamic acid and indole-3-propionic acid play a role in keeping gnavus down in a healthy microbiome. Stay tuned.
I would love to see this tested. But to pre-interpret a possible negative result: Even if you're correct that these microorganisms are causative, they can be a relatively distant immunological or systemic trigger, and the actual symptoms could be caused by neurological damage which will not be treated by removing the bacteria.
Nah man, the whole point of what I'm saying is that this bacterium produces a full agonist at the 2A subtype of the serotonin receptor! And because a lot of work has been done to figure out why some compounds are psychedelic and others are not, we can say with a pretty high degree of confidence that anything which activates 2A is likely to be a hallucinogen.
Exactly my question. As readers of Skolnick likely aware, DIY FMT (as treatment for C Diff infections, oither bowel maladies, or other issues) is controversial but not that hard.
At least *some* schizophrenics likely have sufficient awareness & desire for improvement to consider self-experimentation here. That might quickly hint enough improvement to then do more formal studies.
There *are* consumer fecal biome test offerings – 'TinyHealth' is one – that can give a read on whether a person's R Gnavus is high or not.
But, I suspect you'd need a bunch more data from a broad population of the healthy to have a strong opinion as to whether high R Gnavus – alone, without any other entangled genetic/biome/diet/environment factors – is a reliable indicator of risk in someone who otherwise has no symptoms.
I was wondering when someone who knew about lower GI vasculature would show up! It's a good point, and it raises the question: how long does a bolus stay in that part of the colon?
So, as I understand it, the rectum is a holding pen: we don't poop whenever a bolus of food reaches the end of the GI tract, typically we poop when stretch receptors in the rectum reach a certain degree of pressure. And if someone poops once a day, that means that—if a bolus happens to reach the rectun right after a defecation—it might spend another 24 hours there. Or it might spend no time at all in there, like the last trash bag you load into the can before taking it out to the curb on garbage day.
And suddenly this seems like a double pendulum, the simplest demonstration of chaos theory. If it were as simple as "X hours after you eat high-protein foods, when they reach your rectum, you start to feel crazy", maybe we'd have figured it out by now (although X is probably close to 25h on average, which is just long enough to be really hard to notice without keeping a detailed food x mood journal).
But add in the complication that—if a protein-rich meal was eaten roughly X hours before a dump, it *doesn't* turn into a tryptamine slow drip—and suddenly it's a maddeningly random-seeming thing. Even worse when X+2h is a recipe for 20 hours of tryptamine/phenethylamine infusion, and worse yet when you stop eating because the phenethylamine is suppressing your appetite; idk if you've ever watched Survivor, but a regular feature of every season is people complaining for the first few days about not pooping, since the sudden shift to a starvation-tier diet causes the little food that is eaten to dwell way longer.
You argue persuasively, but it's a really bold claim. Given the fact that case studies have claimed cure (or reduction of symptoms) in bipolar with FMT a similar thing could be happening there (on that note, you should really get samples of Alex Dudley's stools to identify what he has that seems to cure it).
The only flaw in your argument I can think of, assuming your chemistry is right, is that this means we should expect schizophrenics to spontaneously recover with the right sorts of antibiotics, which nobody has reported happening. Unless there's literally nothing that reduces it, which seems unlikely.
Well, in one respect this is another mayonnaise problem (see my other comment on this post): if you have a few psychotic episodes and, after a course of antibiotics, never have another...well, that must not have been schizophrenia, because schizophrenia is by-definition incurable and lifelong once it starts. The book "Brain on Fire" is a spectacular case study; a journalist goes insane for a month or two and spontaneously makes a total recovery. The doctors retroactively diagnose it as some kind of autoimmune encephalitis IIRC.
Interestingly enough, the book contains a scan of a handwritten note she took during one of her doctor's visits during the episode. It's largely incoherent, but one thing that jumped out at me was the disconnected phrase "put be antibiotic" scrawled on the page, which sounds like what I might write if I were trying diligently to take notes while on 50mg of 2C-E and someone told me "We're going to put you on an antibiotic". It's not mentioned anywhere else in the text, presumably because antibiotics are such a common thing that even she—in poring over her own case file for clues from the time which she has no memory of—didn't think it was relevant.
I should also point out that many patients experience years-long remissions where their positive symptoms are more or less fully under control, but typically they don't stop taking their meds. Because a severe dopamine depletion appears to be a major component of the negative symptoms, and the drugs used to treat the positive symptoms are dopamine antagonists...you can see why it'd be hard to suss out the recovery signal from the noise.
See my previous post on MS as well for a tangential but related discussion of why you might not expect spontaneous recovery where an organism has a solid fitness advantage, like the ability to burn the most complex and energetically expensive amino acid, to prevent any potential competitors from using it.
I want to be sympathetic to the anecdote but I'm struggling to find the handwritten note evidence very compelling. People in psychosis say and write a lot of random stuff for reasons you'll never understand.
Admittedly in the future we'll probably see most mental illnesses not as distinct disorders but as syndromes, but for psychosis in particular it's already known there are many diverse reasons why it may occur, even if the mechanics aren't well understood. Lack of sleep and loneliness among them. But you can narrow down and isolate a more 'pure' schizophrenia by setting the criteria to having 2+ psychotic episodes plus evidence of negative symptoms, no drug use and no mania. Plus a loss of cognitive function, particularly cognitive flexibility, after every episode. This does cut out a lot people who probably do have schizophrenia, but it's a criteria that I suspect has the highest sensitivity, so that works for what we're talking about. I've never heard of such a case achieving full remission off medication.
You can be fairly certain that it's not the drugs masking it for two reasons. 1, because it's actually it's very common for people to go off antipsychotics (as you can imagine, they're not very pleasant, people become convinced they've recovered now etc) and then experience another episode, or experience another episode after a period of time while taking the meds anyway. 2, because the negative symptoms are often far more severe than the dopamine antagonism caused by antipsychotics (otherwise people who take them for bipolar or those who are diagnosed with schizophrenia without negative symptoms would complain about gaining much more severe negative symptoms than they do), so people would still report relief after the right antibiotics.
There could be something to the idea that somehow R. Gnavus in people who suffer psychosis is stronger than its neighbours and that's what's causing the problems. But then you're moving the argument into that it's more an ecosystem problem, which while I find it more convincing, but is much less simplistic. It would also explain why schizophrenics seem to fare better in the developing world, where their diet is probably better.
But there's still problems even with that hypothesis. Like, why haven't we heard any case studies of people recovering from schizophrenia with FMT like they do from bipolar? Why isn't it showing the pattern of increasing strongly over time, like most other conditions where there's a suspected microbiome element like most other mental illnesses, chronic conditions etc. Why is it more prevalent in men?
Hey, okay—it sounds like you're pretty well versed in this stuff. Maybe you're even a psychiatrist! If not, imagine for a moment that you are. And imagine that one day, one of your patients comes in and says to you: "great news, doc—I have cured myself! I no longer need to take my antipsychotics, because I ate my friend's shit, and now I'm all better."
Your first thought is not "wow, if that's true it would be historic", or even "let's run through the PANSS to see if he's for real". Your first thought is "oh I'm in deep shit; I should have had this guy institutionalized months ago. I've failed in my duty of care and if anyone finds out about this I could lose my license." Practically the only course of action that *doesn't* leave you open to a malpractice lawsuit is to discreetly reach for the button that summons the orderlies with a straightjacket.
And I'm not even saying it's happened and we just haven't heard about it—probably nobody has even tried it, because unless you're on the bleeding edge of microbiome science, it sounds fucking crazy! It sounds *cuckoo bananas*, and if you have a diagnosis of schizophrenia, you don't have the social license to get away with "it's just crazy enough to work 😈".
I mean, imagine you had a sibling with schizophrenia, and they asked you to shit for their home FMT.
Would you do it? What percent of the population do you think *would*?
You have to be both well-educated on this particular topic and ballsy to the point of recklessness to try something like that when it's a total dead zone in the literature—unless the case is mild enough that you're not really worried about them, in which case it probably wouldn't meet your standard for "actual schizophrenia" anyway.
All I'm saying is that the number of people in a position to even try it is so vanishingly small that the absence of positive reports is not a good argument against its plausibility.
Okay, a little skepticism I appreciate to the extent that that it helps us probe things out, but at this point it seems like you're not reading carefully. I have read the bipolar case report, dude! And what I'm saying is that, because these are considered two different diseases, people with them are treated very differently when they start saying crazy-sounding things. And perhaps more importantly: they often *think* quite differently. You say it yourself: Schizophrenia is uniquely associated with cognitive deficits and cognitive rigidity. A home FMT, meanwhile, is probably the most high-agency thing a person can do: it requires rationally overcoming some of the absolute strongest social taboos! So when you then ask "why haven't I heard of anyone with this disease curing themselves", it's a little like asking "why are there no quadriplegic neurosurgeons fixing their own spines?"
Sorry, this would probably been a much better discussion to have in person. I'm not a psychiatrist, but I have worked in the field. It's easier to courteous with someone and point out that they don't really understand the topic their discussing when you can give body language signals and interrupt them before they say something that's less constructive. Apologies if I come off hostile, I'm trying to attack your position, not you.
How many schizophrenics have you met? How many have you read about? By your own admission they can recover with medication, so therefore be reliable sources on their own internal experience. The link I posted shows that psychiatrists can take FMT seriously, and in a similar condition they can observe the results and accept them, even though bipolar is considered a lifelong disease. You could make a similar argument that psychiatrists could dismiss any patient with bipolar claiming to be cured to be manic.
The reason they can trust that someone is not manic is the same reason they can trust someone is not psychotic. It's usually pretty obvious, especially if you have a positive rapport with that person. And even if you think their ok when they're not, within the ensuring weeks you'll find out because their life will fall apart.
Even if you cannot be certain that a person has been cured or their condition has been improved by FMT, we should by your logic expect an improvement in negative symptoms. Psychiatrists would take that report very seriously, and will most likely be able to be able to observe the change just through behaviour. As you can imagine, psychiatrists rely heavily on observing behaviour for their assessments, so if a patient's behaviour suddenly improves for any reason they take that very very seriously, just like they do for anything that causes a degradation in behaviour.
Schizophrenics are not the drooling invalids you seem to make them out to be. I wanted to find an old article I had read about a psychologist who subsequently developed schizophrenia, recovered with medication and then returned back to work. I wasn't able to find that, but I found this, https://www.glamour.com/story/this-is-what-its-like-to-live-with-paranoid-schizophrenia which shows a similar story of someone who still seems to have been able to life a fulfilling life inbetween their episodes of psychosis. Here's another one https://yennpurkis.home.blog/. Despite their simple style of writing, their actually quite accomplished.
I have not. From a brief skim of the promo site for the book, it seems like he's on the right track but missing some key pieces of the puzzle, in terms of why metabolic dysfunction would induce this particular phenotype, and what separates those who are struck by it from those who aren't.
The man is simply on the wrong side of the Dunning-Kruger curve here. He and I both know a great deal about biological psychiatry and the genomics of schizophrenia. But he knows next to nothing about the gut microbiome, so he doesn't know what a rock solid hit he is writing off as "pshh, it's probably the clozapine, they say it right there in the paper!".
I'll do a point-by-point teardown when I'm done with lab stuff for the day. Sign up to stay posted!
I'm curious if anyone knows a good resource (or resources) to start learning about all the things mentioned in this article - namely interactions between compounds, how the body uses all these different types of things to regulate itself etc...
I find that I get the basics but once enzyme and molecular names come out I quickly lose myself in the weeds and I would love to get a deeper understanding of it in a way that doesn't require me to do a full biology university degree.
To a very large extent, schizophrenia is postural (and I rely on personal experience here). There are two types; hyperextended/flatback (shoulder collapse) and bicameral (shoulders up, tailbone up and back, chin up). My diet is perfectly fine; I don't think schizophrenia has anything to do with diet.
The proof of this is that the purpose of the chin (as a sleeping rest) is censored in academia/search engines.
This is all pretty unlikely. For one, there is very rapid down-regulation of 5HT2* as any user of psychedelics knows.
Another: the experience of schizophrenia and especially the first experience is nothing at all like the serotonin-receptor psychedelics. This was very well researched in the 50s and was abandoned for this and many other reasons.
More damning: long term stimulation of 5HT2A directly causes coronary valve disease (sorry, microdoser) and there is no evidence I can find that schizophrenics have a higher incidence.
Okay, so if you want to get into the nitty gritty: I just saw a talk on this at this year's Winter Conference on Brain Research in Tahoe, and it looks like you only get valve disease when the half life of the agonist is long enough that concentrations in the bloodstream never drop to zero. I'll try and find my notes from it so I can get you the researcher's name, but my takeaway was that this is why daily methamphetamine use is so much worse than daily amphetamine use for CV risk.
I don't think that is correct. In both the MDMA and fenfluramine cases it goes to zero and yet we have observed the disease.
Fitzgerald LW, Burn TC, Brown BS, Paterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW. Possible role of valvular serotonin 5-HT2B receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol. 2000;57:75–81.
Really interesting. Have you seen this paper from 2003 that predicted that schizophrenia would turn out to be caused by microbes? https://muse.jhu.edu/pub/1/article/44812/summary. Part of the evidence they cited was higher incidence of schizophrenia in people born in the winter. Do you know if Ruminococcus gnavus has any seasonal fluctuations in prevalence that could explain this?
Another interesting point: the strongest human genetic signal for schizophrenia is in the HLA genes. As are most infectious diseases, if run a GWAS for them.
Holy shit you might have actually done it. If you're right about this you deserve a Nobel prize.
Woah. Does this imply that a fecal microbiome transplant, from a source with zero-to-low levels of Ruminococcus gnavus, would be sufficient to cure schizophrenia?
It would have to be the right protocol—heavy antibiotic pretreatment, moviprep for good measure, anaerobically prepared donor material etc.—but yes. There may be alternatives to FMT, though; a bacteriophage active against gnavus, maybe some things that are antagonistic to its growth or the activity of the AADC enzyme. I suspect that hydrocinnamic acid and indole-3-propionic acid play a role in keeping gnavus down in a healthy microbiome. Stay tuned.
I would love to see this tested. But to pre-interpret a possible negative result: Even if you're correct that these microorganisms are causative, they can be a relatively distant immunological or systemic trigger, and the actual symptoms could be caused by neurological damage which will not be treated by removing the bacteria.
Nah man, the whole point of what I'm saying is that this bacterium produces a full agonist at the 2A subtype of the serotonin receptor! And because a lot of work has been done to figure out why some compounds are psychedelic and others are not, we can say with a pretty high degree of confidence that anything which activates 2A is likely to be a hallucinogen.
I hope you're right and it's a direct cause that can be directly remedied.
Exactly my question. As readers of Skolnick likely aware, DIY FMT (as treatment for C Diff infections, oither bowel maladies, or other issues) is controversial but not that hard.
At least *some* schizophrenics likely have sufficient awareness & desire for improvement to consider self-experimentation here. That might quickly hint enough improvement to then do more formal studies.
How might I use this information to help someone I know (or test whether they could be helped)? Or test whether someone is at risk?
US-based? Shoot me an email, I'll send the metagenomics sampling kit.
There *are* consumer fecal biome test offerings – 'TinyHealth' is one – that can give a read on whether a person's R Gnavus is high or not.
But, I suspect you'd need a bunch more data from a broad population of the healthy to have a strong opinion as to whether high R Gnavus – alone, without any other entangled genetic/biome/diet/environment factors – is a reliable indicator of risk in someone who otherwise has no symptoms.
The vast majority of the colonic venous return still undergoes first pass metabolism. Only the distal part of the rectum bypasses it.
I was wondering when someone who knew about lower GI vasculature would show up! It's a good point, and it raises the question: how long does a bolus stay in that part of the colon?
So, as I understand it, the rectum is a holding pen: we don't poop whenever a bolus of food reaches the end of the GI tract, typically we poop when stretch receptors in the rectum reach a certain degree of pressure. And if someone poops once a day, that means that—if a bolus happens to reach the rectun right after a defecation—it might spend another 24 hours there. Or it might spend no time at all in there, like the last trash bag you load into the can before taking it out to the curb on garbage day.
And suddenly this seems like a double pendulum, the simplest demonstration of chaos theory. If it were as simple as "X hours after you eat high-protein foods, when they reach your rectum, you start to feel crazy", maybe we'd have figured it out by now (although X is probably close to 25h on average, which is just long enough to be really hard to notice without keeping a detailed food x mood journal).
But add in the complication that—if a protein-rich meal was eaten roughly X hours before a dump, it *doesn't* turn into a tryptamine slow drip—and suddenly it's a maddeningly random-seeming thing. Even worse when X+2h is a recipe for 20 hours of tryptamine/phenethylamine infusion, and worse yet when you stop eating because the phenethylamine is suppressing your appetite; idk if you've ever watched Survivor, but a regular feature of every season is people complaining for the first few days about not pooping, since the sudden shift to a starvation-tier diet causes the little food that is eaten to dwell way longer.
You argue persuasively, but it's a really bold claim. Given the fact that case studies have claimed cure (or reduction of symptoms) in bipolar with FMT a similar thing could be happening there (on that note, you should really get samples of Alex Dudley's stools to identify what he has that seems to cure it).
The only flaw in your argument I can think of, assuming your chemistry is right, is that this means we should expect schizophrenics to spontaneously recover with the right sorts of antibiotics, which nobody has reported happening. Unless there's literally nothing that reduces it, which seems unlikely.
Well, in one respect this is another mayonnaise problem (see my other comment on this post): if you have a few psychotic episodes and, after a course of antibiotics, never have another...well, that must not have been schizophrenia, because schizophrenia is by-definition incurable and lifelong once it starts. The book "Brain on Fire" is a spectacular case study; a journalist goes insane for a month or two and spontaneously makes a total recovery. The doctors retroactively diagnose it as some kind of autoimmune encephalitis IIRC.
Interestingly enough, the book contains a scan of a handwritten note she took during one of her doctor's visits during the episode. It's largely incoherent, but one thing that jumped out at me was the disconnected phrase "put be antibiotic" scrawled on the page, which sounds like what I might write if I were trying diligently to take notes while on 50mg of 2C-E and someone told me "We're going to put you on an antibiotic". It's not mentioned anywhere else in the text, presumably because antibiotics are such a common thing that even she—in poring over her own case file for clues from the time which she has no memory of—didn't think it was relevant.
I should also point out that many patients experience years-long remissions where their positive symptoms are more or less fully under control, but typically they don't stop taking their meds. Because a severe dopamine depletion appears to be a major component of the negative symptoms, and the drugs used to treat the positive symptoms are dopamine antagonists...you can see why it'd be hard to suss out the recovery signal from the noise.
See my previous post on MS as well for a tangential but related discussion of why you might not expect spontaneous recovery where an organism has a solid fitness advantage, like the ability to burn the most complex and energetically expensive amino acid, to prevent any potential competitors from using it.
She had anti-NMDA encephalitis iirc; it is very very specific but the antibody test is almost never done.
I want to be sympathetic to the anecdote but I'm struggling to find the handwritten note evidence very compelling. People in psychosis say and write a lot of random stuff for reasons you'll never understand.
Admittedly in the future we'll probably see most mental illnesses not as distinct disorders but as syndromes, but for psychosis in particular it's already known there are many diverse reasons why it may occur, even if the mechanics aren't well understood. Lack of sleep and loneliness among them. But you can narrow down and isolate a more 'pure' schizophrenia by setting the criteria to having 2+ psychotic episodes plus evidence of negative symptoms, no drug use and no mania. Plus a loss of cognitive function, particularly cognitive flexibility, after every episode. This does cut out a lot people who probably do have schizophrenia, but it's a criteria that I suspect has the highest sensitivity, so that works for what we're talking about. I've never heard of such a case achieving full remission off medication.
You can be fairly certain that it's not the drugs masking it for two reasons. 1, because it's actually it's very common for people to go off antipsychotics (as you can imagine, they're not very pleasant, people become convinced they've recovered now etc) and then experience another episode, or experience another episode after a period of time while taking the meds anyway. 2, because the negative symptoms are often far more severe than the dopamine antagonism caused by antipsychotics (otherwise people who take them for bipolar or those who are diagnosed with schizophrenia without negative symptoms would complain about gaining much more severe negative symptoms than they do), so people would still report relief after the right antibiotics.
There could be something to the idea that somehow R. Gnavus in people who suffer psychosis is stronger than its neighbours and that's what's causing the problems. But then you're moving the argument into that it's more an ecosystem problem, which while I find it more convincing, but is much less simplistic. It would also explain why schizophrenics seem to fare better in the developing world, where their diet is probably better.
But there's still problems even with that hypothesis. Like, why haven't we heard any case studies of people recovering from schizophrenia with FMT like they do from bipolar? Why isn't it showing the pattern of increasing strongly over time, like most other conditions where there's a suspected microbiome element like most other mental illnesses, chronic conditions etc. Why is it more prevalent in men?
Hey, okay—it sounds like you're pretty well versed in this stuff. Maybe you're even a psychiatrist! If not, imagine for a moment that you are. And imagine that one day, one of your patients comes in and says to you: "great news, doc—I have cured myself! I no longer need to take my antipsychotics, because I ate my friend's shit, and now I'm all better."
Your first thought is not "wow, if that's true it would be historic", or even "let's run through the PANSS to see if he's for real". Your first thought is "oh I'm in deep shit; I should have had this guy institutionalized months ago. I've failed in my duty of care and if anyone finds out about this I could lose my license." Practically the only course of action that *doesn't* leave you open to a malpractice lawsuit is to discreetly reach for the button that summons the orderlies with a straightjacket.
And I'm not even saying it's happened and we just haven't heard about it—probably nobody has even tried it, because unless you're on the bleeding edge of microbiome science, it sounds fucking crazy! It sounds *cuckoo bananas*, and if you have a diagnosis of schizophrenia, you don't have the social license to get away with "it's just crazy enough to work 😈".
I mean, imagine you had a sibling with schizophrenia, and they asked you to shit for their home FMT.
Would you do it? What percent of the population do you think *would*?
You have to be both well-educated on this particular topic and ballsy to the point of recklessness to try something like that when it's a total dead zone in the literature—unless the case is mild enough that you're not really worried about them, in which case it probably wouldn't meet your standard for "actual schizophrenia" anyway.
All I'm saying is that the number of people in a position to even try it is so vanishingly small that the absence of positive reports is not a good argument against its plausibility.
https://www.microbiomeinmind.com.au/
Okay, a little skepticism I appreciate to the extent that that it helps us probe things out, but at this point it seems like you're not reading carefully. I have read the bipolar case report, dude! And what I'm saying is that, because these are considered two different diseases, people with them are treated very differently when they start saying crazy-sounding things. And perhaps more importantly: they often *think* quite differently. You say it yourself: Schizophrenia is uniquely associated with cognitive deficits and cognitive rigidity. A home FMT, meanwhile, is probably the most high-agency thing a person can do: it requires rationally overcoming some of the absolute strongest social taboos! So when you then ask "why haven't I heard of anyone with this disease curing themselves", it's a little like asking "why are there no quadriplegic neurosurgeons fixing their own spines?"
You need hands for that!
Sorry, this would probably been a much better discussion to have in person. I'm not a psychiatrist, but I have worked in the field. It's easier to courteous with someone and point out that they don't really understand the topic their discussing when you can give body language signals and interrupt them before they say something that's less constructive. Apologies if I come off hostile, I'm trying to attack your position, not you.
How many schizophrenics have you met? How many have you read about? By your own admission they can recover with medication, so therefore be reliable sources on their own internal experience. The link I posted shows that psychiatrists can take FMT seriously, and in a similar condition they can observe the results and accept them, even though bipolar is considered a lifelong disease. You could make a similar argument that psychiatrists could dismiss any patient with bipolar claiming to be cured to be manic.
The reason they can trust that someone is not manic is the same reason they can trust someone is not psychotic. It's usually pretty obvious, especially if you have a positive rapport with that person. And even if you think their ok when they're not, within the ensuring weeks you'll find out because their life will fall apart.
Even if you cannot be certain that a person has been cured or their condition has been improved by FMT, we should by your logic expect an improvement in negative symptoms. Psychiatrists would take that report very seriously, and will most likely be able to be able to observe the change just through behaviour. As you can imagine, psychiatrists rely heavily on observing behaviour for their assessments, so if a patient's behaviour suddenly improves for any reason they take that very very seriously, just like they do for anything that causes a degradation in behaviour.
Schizophrenics are not the drooling invalids you seem to make them out to be. I wanted to find an old article I had read about a psychologist who subsequently developed schizophrenia, recovered with medication and then returned back to work. I wasn't able to find that, but I found this, https://www.glamour.com/story/this-is-what-its-like-to-live-with-paranoid-schizophrenia which shows a similar story of someone who still seems to have been able to life a fulfilling life inbetween their episodes of psychosis. Here's another one https://yennpurkis.home.blog/. Despite their simple style of writing, their actually quite accomplished.
Curious if you have read Brain Energy by Chris Palmer and if yes, how do you situate your theory in relation to his work?
I have not. From a brief skim of the promo site for the book, it seems like he's on the right track but missing some key pieces of the puzzle, in terms of why metabolic dysfunction would induce this particular phenotype, and what separates those who are struck by it from those who aren't.
It's literally called Ruminococcus. Ruminate. For people hearing voices. Nominative determinism strikes again!
Nominiative determinism is naming an organ the "appendix" before you knew it actually maintained a list of everything in the biological book lol.
Sorry, I just don't think that this really works for all of the reasons Scott points out here: https://www.astralcodexten.com/p/contra-skolnick-on-schizophrenia
Very curious if Skolnick has a response to AC’s pretty damning takedown of his theory.
The man is simply on the wrong side of the Dunning-Kruger curve here. He and I both know a great deal about biological psychiatry and the genomics of schizophrenia. But he knows next to nothing about the gut microbiome, so he doesn't know what a rock solid hit he is writing off as "pshh, it's probably the clozapine, they say it right there in the paper!".
I'll do a point-by-point teardown when I'm done with lab stuff for the day. Sign up to stay posted!
Look forward to the back and forth
I'm curious if anyone knows a good resource (or resources) to start learning about all the things mentioned in this article - namely interactions between compounds, how the body uses all these different types of things to regulate itself etc...
I find that I get the basics but once enzyme and molecular names come out I quickly lose myself in the weeds and I would love to get a deeper understanding of it in a way that doesn't require me to do a full biology university degree.
(Perhaps a book or lecture series or something?)
Thanks in advance if you know anything!
Molecules and Mental Illness by Samuel Barondes. I'll send you my copy if you want
I'll find a copy myself. Thanks for the rec!
https://archive.org/details/moleculesmentali0000baro_l6q3
Looks like you can check it out for free on Archive.org!
To a very large extent, schizophrenia is postural (and I rely on personal experience here). There are two types; hyperextended/flatback (shoulder collapse) and bicameral (shoulders up, tailbone up and back, chin up). My diet is perfectly fine; I don't think schizophrenia has anything to do with diet.
The proof of this is that the purpose of the chin (as a sleeping rest) is censored in academia/search engines.
what about IBS and related anxiety? Is there a treatment
Any idea of correlation with GERD or Borderline?
This is all pretty unlikely. For one, there is very rapid down-regulation of 5HT2* as any user of psychedelics knows.
Another: the experience of schizophrenia and especially the first experience is nothing at all like the serotonin-receptor psychedelics. This was very well researched in the 50s and was abandoned for this and many other reasons.
More damning: long term stimulation of 5HT2A directly causes coronary valve disease (sorry, microdoser) and there is no evidence I can find that schizophrenics have a higher incidence.
>there is no evidence I can find that schizophrenics have a higher incidence
Look harder.
They have lots of cardiac issues, often due to smoking, _but not that one_.
Okay, so if you want to get into the nitty gritty: I just saw a talk on this at this year's Winter Conference on Brain Research in Tahoe, and it looks like you only get valve disease when the half life of the agonist is long enough that concentrations in the bloodstream never drop to zero. I'll try and find my notes from it so I can get you the researcher's name, but my takeaway was that this is why daily methamphetamine use is so much worse than daily amphetamine use for CV risk.
I don't think that is correct. In both the MDMA and fenfluramine cases it goes to zero and yet we have observed the disease.
Fitzgerald LW, Burn TC, Brown BS, Paterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW. Possible role of valvular serotonin 5-HT2B receptors in the cardiopathy associated with fenfluramine. Mol Pharmacol. 2000;57:75–81.
Montastruc F, Montastruc G, Vigreux P, Bruneval P, Guilbeau-Frugier C, Cron C, Bagheri H, Delisle B, Lapeyre-Mestre M, Pathak A, Montastruc JL. Valvular heart disease in a patient taking 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'). Br J Clin Pharmacol. 2012 Sep;74(3):547-8. doi: 10.1111/j.1365-2125.2012.04252.x. PMID: 22364182; PMCID: PMC3477357.
I'm curious if you suspect this is also applicable to bipolar I. Would love to test my shit.
Very probably, at least in some cases! Either way, curious to get a look at what you've got going on. Shoot me an email, sdskolnick@gmail.com
Really interesting. Have you seen this paper from 2003 that predicted that schizophrenia would turn out to be caused by microbes? https://muse.jhu.edu/pub/1/article/44812/summary. Part of the evidence they cited was higher incidence of schizophrenia in people born in the winter. Do you know if Ruminococcus gnavus has any seasonal fluctuations in prevalence that could explain this?
Another interesting point: the strongest human genetic signal for schizophrenia is in the HLA genes. As are most infectious diseases, if run a GWAS for them.
this is fascinating stuff! also check this out - https://www.sciencealert.com/an-early-warning-signal-of-a-silent-killer-cancer-may-hide-in-your-poop