I have schizoaffective disorder, induced by a bad trip from marijuana. It was like the 3rd time I had tried weed, and I naively took too much.
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...
As someone who is currently dating someone with history of psychosis, I have vested interest.
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.
Isn't it due to synaptic pruning going wrong, a sort of off-by-one error of a gene tagging synapses for deletion?
Very worth it to read the follow up research paper that moves away from this cliff-edge hypothesis, highlights other ambiguities, and attempts some self-correction.
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.
If genes that increase schizophrenic risk increases cognitive abilities you should find people who have high polygenic scores for schizophrenia without having schizophrenia test well on these cognitive abilities. I'm not aware of any of data that shows this in a convincing matter. I think I've seen a few small studies but nothing that replicated this on a large scale. And most of the studies show they score worse on cognitive abilities.
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.
Is it possible that the pro-schizophrenia genes persist because they offer other (non-neurological) benefits, e.g., lower risk of cancer? Siblings of patients with schizophrenia are less likely to develop cancer, and in several studies these patients had lower risk of developing cancer despite higher prevalence of smoking.
For your consideration: the theory of "Positive Disintegration" developed by Kasimir Dabrowski does help to explain the capacity and reality of schizotypal disorders. The easiest way to explain it, is that human brain potential for "over-excitation" leads to personality development; this is natural and human. The stages of personality development are not guaranteed to succeed and proceed correctly. Most cases of schizophrenia may be a result of failed re-organization, or a failure to develop the final, executive, function. In cases of "arrested development," this process may be delayed till later in life. This is the so-called mid-life-crisis, which also can fail, and then you get adult onset schizophrenia. This is all emerging research thats usually locked up in foreign language journals. Almost no medicine to be sold here, AMA and APA are not interested...
Maybe this could explain why mental illness & creativity seem to be so closely related? Just as one example, James Joyce's daughter was schizophrenic.
The article suggests a possible model where the schizophrenia is an extreme linear progression. But the inability to find a culprit genes suggests something more complex. It is possible that there are is a group of genes that all have variations that confers benefit, but when those variations are all together negative effects occur. That makes the positive variants overall beneficial, and keeps them in the gene pool. This is why it is dangerous to presume that when we correlate genetic variants with disease and then presume they should go away. In fact, nearly any inherited disease that has survived may be conferring value to other individual when in proper partnership with other genetic profiles.
After reading this article, I’m really curious how you would model all kinds of other reproduction reducing behaviors that have become popular in recent years and how they many generations it will take them to be squeezed out of our culture. Like say taking care of a pet instead of having a kid in Korea.
Though it doesn’t mention it by name exactly, I think a related idea for systems that are optimized close to a point of phase change is “the edge of chaos”
>The persistence of schizophrenia is an evolutionary enigma
how much schizophrenia is actually going to manifest in peak procreating years?
I think people should study the RCCX gene cluster and link to giftedness more, I have TNXB SNPs which results in hEDS, but C4 SNPs have a similar effect and is likely to result in Schizophrenia. There are some cross over symptoms such as dopamine dysregulation and flat affect. I think dysautonomia and auto-immune plays a big part. Our lifestyles are very different than they used to be and this could be exacerbating auto-immune issues and as we get better at treating auto-immune conditions I expect we'll get better at treating Schizophrenia.
Schizophrenia can coexist with extreme levels of intelligence and lucidity.
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.
Why does no-one dare say "schizotypy?"
I wonder if Autism would be even simpler to explain with a cliff-edged fitness function. Because there seems to be a high correlation between extremely intelligent people and people on the spectrum. Maybe the group of genes rewarded for high intelligence/creativity/quantitative ability also, by accidental design, inhibits social capacity.
Completely anectodal:
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).
Random layperson musing:
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.
Julian Jaynes' theory is always interesting to think about. I self-diagnosed myself as schizophrenic in my late teens and I still stand by my diagnosis 20 years later. I do believe it is a spectrum though and the degree to which one is schizophrenic is not static, and I don't think it's even necessarily a bad thing.
The cliff theory is an interesting one. I don't have any kind of schizo propensity, to my knowledge, but I did, for a brief period of my life, have what I call a "firemind" experience.
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.
As expected a lot of the comments here are anecdotes. I’m assuming there exists a class of highly technical articles that get posted regularly that incite ancillary discussion, but no real contribution involving the article.
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.
Interesting article. Also a good amount too high above the paygrade for me to decipher all concepts in it, but as someone who had close contact with schizophrenics a lot, I was missing one aspect in particular:
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.
The problem with this whole line of thought is that the human environment since the neolithic period has changed.
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.
Schizophrenia is genetic. So you're born with it. This makes zero sense. Maybe you mean shizo-effective which usually has to do with traumas.
I've lost one of my best friends to what I think is schizophrenia. We don't know because she's cut off all contact with friends and family and refuses to see a doctor. It's definitely psychosis. She thinks she's in some kind of Truman show that she calls "the game". Since none of her friends or family are willing to admit to it, then we must be in on it.
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.