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Posted by Anon84 6/28/2025

Schizophrenia is the price we pay for minds poised near the edge of a cliff(www.psychiatrymargins.com)
262 points | 396 commentspage 3
bryanrasmussen 6/29/2025|
>The persistence of schizophrenia is an evolutionary enigma

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

rozab 6/29/2025||
Reproductive fitness does not end as soon as offspring are born. Maximising the likelihood of genetic continuation is a lifelong endeavor.
throw-qqqqq 6/29/2025||
I have two relatives with schizophrenia. Both had onset in their mid 20s.
bryanrasmussen 6/29/2025||
yeah but a sizeable part of the discussion here has been about women with menopause starting to show schizophrenic behaviors. So that might be a significant amount of the schizophrenic cases in the population.
throw-qqqqq 6/29/2025||
> So that might be a significant amount of the schizophrenic cases in the population

I dont think they are. Most are diagnosed in their teens or early twenties. Women slightly later than men.

Women diagnosed in their menopause are not a majority of diagnosed schizophrenics; far from.

I understood that part as merely a curiosity.

bryanrasmussen 6/30/2025||
OK, I just figured if there were specific large groups of schizophrenics that manifested outside of prime procreative years that it might be a reason for it to not be such an evolutionary mystery. Of course it was unlikely this was the case as surely some of the people claiming evolutionary mystery would have thought of it and ran the data.
user395929935 7/2/2025||
This makes good sense in my experience. I was struggling socially and academically in college so they proctored an IQ test to look for things like ADHD etc. I scored in the 98th percentile for verbal comprehension. Only 2 years later did I have my first psychosis and was diagnosed with Schizoaffective. Luckily after a few rough years I'm doing well on the lowest dose of an antipsychotic and can function in society again. But there are definitely cases of highly creative or people with strong language skills that the expression goes too far like this post suggests.
daft_pink 6/28/2025||
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.
sandspar 6/29/2025|
One plausible explanation is that birth and childhood have become much less dangerous. Before 1900, children with poor genes died; since 1900, children with poor genes survive and have children of their own.
rixed 6/29/2025||
My understanding of high child mortality rates in the past is that it has little to do with genetics, and more to do with infectious diseases and poor hygiene.
sakoht 6/29/2025||
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.
FollowingTheDao 6/29/2025|
This is true for every population. For instance, the price of protecting many African populations from malaria is sickle cell disease.

But I think environment plays a bigger role in modern society to increase the risk of mood disorders than genetics alone.

Mistletoe 6/29/2025||
> Let’s say schizophrenia is associated with a 50% loss of reproductive fitness in 1% of the population (and there is no offsetting benefit in the rest of the population), then it would take roughly 180 generations to cut the rate in half and about 560 generations to reduce it to one-tenth of its original value (Mitteroecker & Merola, 2024). We’ve had a comparable number of generations since the Neolithic era, but as far as we know, the prevalence of schizophrenia has not decreased in the manner anticipated.

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.

cjbgkagh 6/28/2025||
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.
PaulHoule 6/28/2025|
Is there some puzzling chronic condition that isn’t on this list?

https://me-pedia.org/wiki/RCCX_Genetic_Module_Theory

cjbgkagh 6/28/2025||
Of course there are. I'm guessing you're insinuating two things, it's highly improbable that individuals can have this many simultaneous issues, and it's impossible for medical researchers to miss such an anomaly. The Ehlers Danlos subset is shorter but still covers a huge amount of issues (https://ohtwist.com/about-eds/comorbidities).

Well there is a reason why doctors kept telling me I am a hypochondriac, but I do have a whole zoo of conditions simultaneously, and this is a pretty common state for people with hEDS and I'm on the extreme end of it. So while milder versions of it are ~2% of the population the extreme versions of it are < 1/20K.

And yeah, medical researchers are in fact in the aggregate really bad at their jobs. Look how long it took to convince surgeons to wash their hands. But a lot of the genetic stuff relies on Linear Regression for GWAS which assumes independents of SNPs, otherwise you get multicollinearity problems, this is not a safe assumption and they've confused their results as confirming their assumptions. Instead of listing everything they get wrong a much shorter list is what they get right, Dr Jessica Eccles (https://x.com/BendyBrain) does great research into Long Covid and Generalized Joint Hypermobility which should put to bed the theory that GJH is benign - still good luck trying to talk a doctor out of that train of thought.

If you find someone who has hEDS the odds are they have a very large number of those things and most of them don't even know the names of most of the conditions, just one or two that bother them the most. The RCCX / hEDS list is a distinct subset of all possible things, the list of all medical maladies is far longer. It becomes highly improbable that a set of people have the same set of maladies - doctors tend to chalk this up to social contagion but that doesn't bear out. Genetic and behavioral causes have distinct diffusion patterns.

It's confirmable with WGS which I've done and I've encouraged many others to do and it turns out that you can indeed predict with a great deal of reliability if someone has TNXB / CYP21A2 SNPs. Unfortunately it's harder to find people who have C4 since they're likely to have schizophrenia.

gavinray 6/29/2025||
Do you have a list of which SNP's are related to this/are pathological?

I have an Ancestry partial genome that I've imputed to expand. Would be curious whether those SNP's are present in the data.

cjbgkagh 6/29/2025||
They are listed as benign, since I find the people first then get the sequence I think that classification is incorrect.
cjbgkagh 6/29/2025||
There are many TNXB SNPs and many are not rare, while I can theorize that the number and severity of the SNPs can explain a spectrum I don't have enough data to prove it. The data that I do have is highly improbable to be from random chance, but not impossible so I'm still collecting and am open to being wrong.
Raphell 6/30/2025||
I know someone who had a clear psychotic break and still hasn't fully recovered. The scariest part wasn't when he lost control. It was that he truly believed everything made perfect sense. The more you tried to care for him, the more he thought you were acting and trying to manipulate him.
r33b33 6/29/2025||
If you have caution and paranoia about potentially being schizophrenic, does that mean it's less likely to manifest due to extreme self-awareness? I have been diagnosed with BPD, psychosis (sometimes) and depression, but I think I'm too aware when it comes to shizhophrenia.
storus 6/29/2025|
Isn't it due to synaptic pruning going wrong, a sort of off-by-one error of a gene tagging synapses for deletion?
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