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We don't know her full family medical history because her dad was adopted. I do know that she was "microdosing" and macro-dosing hallucinogens for years. Mostly acid and shrooms as far as I know. She followed the band Phish around with a group of friends. I can't imagine most of those shows were sober.

We've also seen a few incidents of paranoia when she was under the influence of drugs/alcohol going back decades. So it feels like this was always there in some form, but maybe the estrogen was holding it back before menopause hit. I read an article about women who get schizophrenia after menopause that suggested this could be the case.

Anyway, whenever I see wellness healers and the like extolling the virtues of psilocybin, I want to point out that there could be a downside. We don't know that all of her hallucinogen use over the years contributed to this. But it's certainly a possibility.

The only conclusions I've come to are one of the following.

1. They improve cognitive abilities in some way we aren't good at measuring. 2. There is something about our modern environment that is more likely to trigger schizophrenia which has more recently increased the fitness penalty these genes confer.

https://www.psychiatrymargins.com/p/the-evolutionary-genetic...

In any case, a fascinating read and well-worth it to explore the linked citations, especially by Crow and Nesse.

90% of the time she is truly the most amazing, compassionate, full of life and thoughtful person one can ever meet. Then there are times when it’s truly awful. She can barely sleep at all, leaves house without telling anyone seemingly thinking the presence of third person around. And she strongly feels others around are judging her hard, giving non verbal communication. It’s truly awful.

I didn’t know to the full extent her symptoms when we started dating. But one thing that was clear was she could barely sleep at night. Or sleep too long. There was no “normal sleep cycle”.

Over the time, some triggers are noticeable. Places with crowds, bright lighting, or sometimes stress at work. Aripaprazole so far seems to be holding up, no one knows for how long. I hear meds become resistant at some point. I don’t know what future holds. Kids are probably not an option. Although she very much wants it.

Content gets more engagement as it gets closer to the "policy line" of getting banned, and in a competitive information environment (an engagement maximizing algorithm) you end up with a lot of content close to the border of what's allowed.

For me psychosis feels like pattern matching going on extreme overdrive, while at the same time memory goes to shit. It's truly an awful illness, and what's worse is that the current medical treatments are bad. I've been fortunate enough where I can get by on a low dose olanzapine, but for many people they simply don't work at all.

Even though I'm doing well enough to function normally and hold down a good, well paying job, it's impossible to find a partner. If I were to have kids, I would have to go through one of the embryo prescreening services. I am strongly in support of these screening services - the disease is truly horrible.

There has been little progress on treatments for schizophrenia, the mechanism of action of these drugs has remained the same for decades. The side effects are almost as bad as the disease, which is why so many schizophrenic stop taking them. The only novel medication recently released is Cobenfy, which I have not tried yet.

Personally I am holding out hope that schizophrenia has some basis as an autoimmune disease. There was a cancer patient who had a bone marrow transplant and ended up being cured: https://www.nytimes.com/2018/09/29/opinion/sunday/schizophre...

Right after the time I was diagnosed (~36), I started to become weirdly good at some stuff.

Music, for example. I've been playing for almost two decades and couldn't progress after a certain level. This changed almost overnight, and I started to learn new instruments very quickly (now I play guitar, bass, drums and piano). I'm not a genius at them, it's not what I'm trying to say. It's just that the pace at which I learn is very different from when I was younger, I can do things I never imagined being able to do.

Somehow, I also acquired some ambidextry. This might be due to learning the instruments. I now can write with both hands (not at the same time, dominant hand is still faster and more acurate). I also developed a second, completely different handwriting (now I have two "fonts" I can use naturally).

I got worse at dealing with people. Everyone seems to be in a haze from my point of view, and it discourages any kind of meaningful relationship. I can pretend though.

I am highly skeptical of the idea that any genetic component is involved in all of this (my father was ambidextrous though, but he acquired it in childhood), it seems purely psychological. I am also skeptical about the stereotypical triggers people often associate schizophrenia to.

Last year I was reading about Havana Syndrome. That was the thing that most resonated with the kinds of psychotic events I had. Weird sounds and voices that seem to come from nowhere, dizziness, balance problems, insomnia, headaches. By the time I got to a doctor, these effects were not there anymore (they last a very short time, at least for me). I was diagnosed by describing them to the psychiatrist. Since the first episode, it has happened again a handful of times. I have learned since that Havana syndrome is not a thing anymore, but there are no official explanations other than "it's likely to be psychogenic". I also wouldn't qualify for it (apparently, only diplomats and spies had it).

During that period I spent an unhealthy amount of time alone. I also spent tons of time reading. During that time the ability of my brain to free-associate seemed to absolutely explode. I felt like I could see a pattern or form a connection between almost anything whatsoever. I read symbolism in everything. The few times I did see friends during that time, I remember them being kind of shocked at the callbacks, linkages, etc. that I was able to fire off instantaneously at the board game table.

My brian no longer works like this. I underwent several lifestyle changes and it seemed to really rewire me. I'm much more logical in my thinking now, but it's taken practice, and the shift was gradual. Every now and then I kind of miss the "semiotic aptitude" I had in those days, but I wonder if I was really just teetering on the edge of a cliff. Maybe a few more months of isolation would have pushed me over the edge.

A schizophrenic member of my family argued in divorce court that her husband, a leading physician at one of the most famous medical institutions in the world, was secretly involved in outrageous nefarious activities.

The stories were all fiction but she was so convincing that the judge awarded her a ruling in the divorce that ruined her husband financially and took an emotional toll.

" We must remember that we are living in an age in which the ground is shifting and the foundations are shaking. I cannot answer for other times and places. Perhaps it has always been so. We know it is true today. In these circumstances, we have all reason to be insecure. When the ultimate basis of our world is in question, we run to different holes in the ground; we scurry into roles, statuses, identities, interpersonal relations. We attempt to live in castles that can only be in the air, because there is no firm ground in the social cosmos on which to build."

"Sanity today appears to rest very largely on a capacity to adapt to the external world — the interpersonal world, and the realm of human collectivities. As this external human world is almost completely and totally estranged from the inner, any personal direct awareness of the inner world already entails grave risks."

https://en.m.wikipedia.org/wiki/Edge_of_chaos

Homosexuality is interesting from this perspective too - common enough that evolution has to be selecting for it, yet basically fatal to reproduction, so what are the benefits that evolution is selecting for? Is it advantageous to groups, or maybe the same genes confer an individual benefit to non-homosexuals?

https://en.wikipedia.org/wiki/Schizotypy

It also does not take into account the huge amount of human relocation that’s taken place over the last 200 years. For example, we have a large number of Africans that are now living in climate that are much colder than what they evolved to live in. The same as truth for northern Europeans, who lived in cold, cloudy climate now living in sunny, warm climates. Does anyone hear really think that that wouldn’t affect the populations mental health?

We know schizophrenia genes are almost always risk genes, meaning their polygenic, or they don’t cause schizophrenia, and everyone who carries the genetics. There are a very few number of cases of people who carry genes that directly caused schizophrenia.

So it’s quite possible that schizophrenia did not exist as frequently as it does in the modern world, a world filled with pollution, stress, drugs, aldehydes, bad food, and on and on and on.

But let’s just take migration. It is a well-known risk factor for schizophrenia. See the paper below.

https://psychiatryonline.org/doi/pdf/10.1176/appi.ajp.162.1....

So no schizophrenia is not the price we pay for mine poison near the edge of a cliff, it’s the price we pay for technology. The technology that enabled not only all the wonderful things to get, but also all the horrible things that come with it.

I had schizoaffective disorder, and I have essentially cured it. But I really can’t say it’s a cure because what was happening was there was a Mitch match between my genetics in my environment. It’s like curing yourself from celiac by not eating wheat. Celiac is only a disease if you eat wheat.

So I am one of these involuntarily relocated people because of capitalism. My great great grandparents on my mother side were Sami and I still carry those genetics. Changing my environment and changing my diet changed my life. Frankly, I’m tired of these articles saying that there’s no cure for mental illnesses and it’s just a price we pay.

... Okay, but you already acknowledged that

> The process will be slow, but it will happen (this is not the same as saying schizophrenia itself can be eliminated, since it is highly polygenic and the pool of risk genes is not static).

So how do we know that modern-day schizophrenia isn't caused by a different set of genes? Maybe the Neolithic ones have been dying out from the gene pool, but new ones have consistently managed to keep replacing them. New genes can start contributing to the incidence of schizophrenia right away; even if they're otherwise neutral, they but won't die out due to the marginal effect on schizophrenia incidence for a very long time (much longer than the calculation above - since each one is, as we already established, causing only part of the loss in reproductive fitness). They don't need to be under positive selection, unless I've misunderstood something.

https://pubmed.ncbi.nlm.nih.gov/38041862/

I am not an expert by any means, but this analysis only makes sense if we assume there is a strictly linear relationship between alleles. It will not capture nonlinear relationships.

All schizophrenics I know didn’t start as obvious psychopaths, but rather have their personal „cliff“ usually around an age associated with hormonal changes (eg early twenties, menopause).

So in other words the negative selection effects aren’t there until after reproduction.

I wonder if schizophrenia (or perhaps psychosis) could be in some way analogous to the LLM temperature function becoming disregulated?

I mean, what is the extreme opposite of psychosis? If it is matter of degree, which it seems to be, then there is probably a tuning mechanism. Perhaps too little and you fail to account for factors that might not be apparent but might be guessed or inferred, too much, and too much seems plausible.

If so it would be possible to have a great deal of different “causes” given the tight and complex coupling of biological mechanisms.

For me, I don’t like that this is about a mathematical model. I don’t want a mathematical model. I like the theory, and I think it’s interesting. I don’t need further digressions into a model. I want to see the real thing. Prove it, replicate it, codify it.

What if the number we experience now IS 1/10 of what it used to be? Would explain a lot of religious talking to God in the past.

Much the same could be said for gayness. If it were genetic, it should have been eliminated by evolution by now. Which suggests that it's not.

There are some differences in incidence of schizophrenia in populations.[1] Birth order matters, slightly, with prevalence higher for firstborns. (This is the reverse of homosexuality and left-handedness.) Migrants have higher rates of schizophrenia than non-migrants. Women vs. men, about the same. Rural vs. urban, about the same.

What the original paper suggests is that they didn't discover anything significant. It's more like a discussion of feedback control problems near a cliff, but by people who don't know about that part of control theory.

The title is overly dramatic for the results.

[1] https://journals.plos.org/plosmedicine/article?id=10.1371/jo...

how much schizophrenia is actually going to manifest in peak procreating years?