Schizophrenia: The new etiological synthesis | Hacker News Reader

Schizophrenia: The new etiological synthesis

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97 pointsbesmirch121 comments

Fascinating. I self-diagnosed myself with schizophrenia once. A horrible 6 months locked in an alien world where all I could think about was time and space (at about a million miles a second). I would hear chatter in my head and was convinced I was overhearing random conversations people were having and was even certain of the locations they were having these conversations. The idea that we all shared one consciousness and that time and space was an illusion would give me constant panic attacks every day. I would look at tv and faces would warp, become big and small. It was like living inside a nightmare.

But then I broke out of it in an instant 6 months later whilst I was trying to distract my thoughts by focusing on the shoes that peoples were wearing inside a busy train station - I started to find it amusing how silly people looked in certain styles etc. Who knows, I was out of my mind. What a feeling.

I have PTSD from extremely bad psychedelic trips and this comment made me cringe (my PTSD must be getting better because I think at one point it would have given me a panic attack). I don't think I could have handled 6 months of that.

It begun for me after smoking weed one night - in a flash I was outside my body with an extreme panic attack and the sudden belief that I was inside essentially a game. This first panic attack lasted around an hour or two. It was horrendous. Your PTSD is something you can manage, I have it too. It gets better and weaker as the years go on. For myself, this all happened 18 years ago but it made me a stronger person.

Marijuana actually triggers panic attacks in a similar way for me. None of the other psychedelics trigger it as bad as marijuana. Even then it’s a different type of management if it’s from shrooms or lsd. The marijuana one feels psychotic with short term memory loss vs just experiencing a different reality.

Any time you feel the onset of a panic attack, tell yourself it’s just a panic attack. Make yourself think of a happy thought and stay with it. Repeat a mantra in your head “Everything will be alright in the end, if it’s not alright, it’s not the end”. Try to go up and down the alphabet, maybe skipping letters - every 2 letters at a time; a, c, e, g… And backwards. Multiply numbers, etc. And do not smoke bongs, smoke only single skin joints which aren’t packed. These are a few of my techniques.

Cannabis is a very strong (and often unpleasant) psychedelic for someone I know — rivaling LSD if not stronger. I’ve heard of this being true for other people too; I wonder how common it is.

This is why I can only smoke the tiniest bit. And only a couple of times a year - it’s not the same as LSD or mushrooms, but it’s just as intense what it does to my mind.

I always wanted to face my fears instead of run from them. Cannabis definitely gives me super powers, my brain races with a million thoughts and brings out a part of me which needs to escape from time to time - it brings out the best in me (strangely enough).

This is true for me, mainly because the major effect of psychedelic drugs for me is completely 'internal' to my mind. Actually most of my trips are basically just extensions of the last one because I just revert to the same (psychotic) thought patterns. It's a pretty awful place to be which ultimately led to me getting PTSD after smoking a joint and believing some awful stuff about my existence.

You're not the only one, how many of us out there?

Seems like we were the only ones!

I wouldn't have been surprised if there was more though. I think the kind of people on here probably think too much/overanalyze stuff to begin with and my impression is that trait doesn't mix super well with psychedelics.

At least I feel like the fundamental cause of my PTSD inducing trips is wanting to explain the inexplicable.

Hope everything's going well for you though. I think it's especially hard to have this kind of PTSD because people don't take it very seriously and it's either socially embarrassing or triggering to try and talk about it to begin with.

Mine was a long time ago now (~7 years), I was pretty horribly messed up and dysfunctional for the first 2-3 years but I'm mostly okay now. I have HPPD too but that's also mostly subsided, and things only flare up for me if I go without sleep or am under a lot of stress.

Hope you're doing alright too!

I also take Buspirone, which I've found helps a ton with general anxiety.

I can share the sentiment. I got stuck in a few loops on psychedelics and it was tumultuous to say the least. Overall it was a net positive effect but it’s certainly not the only way for “enlightenment.” It’s perhaps the most masochist path to enlightenment. Perhaps Alan Watts said that.

Well we have to learn not to lie to ourselves, one way or another.

Ain't that the truth.

Dang, this did give me a panic attack. The sort of thing OP describes is my greatest fear, and I have a hard time dealing with the fact that it really happens to some people.

To be fair, I suffered anxiety since I was 7 or 8yrs old and had a shitty start at life. That snapping experience was a long time coming for me. Don’t be worrying it will happen to you, cause it’s pointless unless it has happened and it’s not worth the worry.

What you are describing sounds like a protracted psychotic break. Schizophrenia doesn’t just come one day and disappear 6 months later.

Maybe you are right. I watched a Netflix doc on schizophrenia a few days ago, and it was ‘check, check, check’ for nearly every symptom. I suppose there’s a lot of overlap with the more extreme mental health issues.

Having a quick look through this thread just about nothing your describe fits well with traditional psychiatric disorders.

For example panic attacks almost by definition do not last more than 15minutes.

Although self diagnosis is near impossible, I mean how can you expect to be an objective observer of your self when you can barely watch TV? It's possible a trained psychiatrist would be able to make a snap diagnosis for you if they were able to watch and listen to you at the time.

That was just my very first, introductory panic attack.

I did have another which lasted a very very long time when I was outside, but I was given a shot of adrenaline for that one.

The thousands of others have been under 15mins.

You were given a shot of adrenaline for a panic attack?

Not exactly. More like a solo first time trip on 5 acid tabs going horribly wrong. It wasn’t meant to be a solo trip, but my ‘friends’ abandoned me. I tried to go outside because I was absolutely freaking out walking around a busy town, thinking I could distract myself. Then shit hit the fan even worse. It was a terrible trip, put it that way. So more like an extreme long lasting panic attack on top of visual hallucinations. I was 19 and dumb clearly masochistic!

Oh fun fact: When an ambulance was called and they basically dragged me into the hospital bed. As they injected me with adrenaline, that scene from Matrix happened to me as real as day (obv not tho) of when Neo touches the mirror and it goes up his arm and over him - I hallucinated that it was happening to me, watching the cold metalic liquid travelling up my arm. It was quite out there stuff!

None of this makes sense.

Venous delivered adrenaline is used to close down peripheral circulation during cardiac arrest to encourage the poor flow to perfuse the heart, lungs and brain. Maintaining tissue viability until recovery.

Intramuscular adrenaline is used in anaphylaxis.

Either makes sense in the context you describe. I must be missing something.

Are you misremembering stuff?

I have been certain for 17 years that they said it was adrenaline.

If it wasn’t adrenaline, what else could it be? I went in and out of waves of in outside this world to inside the room to outside this world and inside the room. Until I was firmly inside the room and out if the trip. It was fast.

And it was into my vein, they tied a rubber hose around my arm. I watched the needle go in. And I had to hide my arm for weeks cause it looked like I injected - all bruised and stuff. Few holes. Must have missed with me moving about.

I also have a vivid memory of the heart beat monitor showing 240!

Adenosine? Used to revert a supraventricular tachycardia.

Name sounds enough like adrenaline to mix them up, and would have felt like death. Adenosine is rapidly metabolised so it needs to be delivered into a reasonably large vein and pushed with a bolus so I can't imagine it wrecking your arm where the cannula was placed.

I think you might be onto something with the name mixup. I reckon you might be right - thank you!

And I looked up cannula and bolus, but I only remember a syringe with a needle attached to it. My memory might be wrong though.

That scene (the matrix mirror) sounds more entertaining than my pulp fiction reenactment (the OD scene - I died and then sat up just as they were gonna stick me with the atropine).

I would prefer yours for sure. Back from the dead… that is out there!

Not usually, but schizophrenia is a waxing and waning disease like MS - patients tend to get episodes of worsening symptoms then remission (partial) where symptoms get better. Then they’ll get another relapse and often it’s worse, eventually resulting in a state of chronic symptoms.

Treatment with antipsychotic medication can actually “pause” the cycles and prevent the disease from getting worse if started early. It’s definitely a progressive disease.

I always thought of schizophrenia as a disease you just got and always had.

Schizophrenia is a degenerative condition where positive symptoms start to be replaced by negative symptoms over the course of years. I've worked in acute adult mental health, and did a few shifts in the long term wards and the difference between people earlier on in the course of their illness versus the end stages are stark.

I would so love to chat with someone with your experience. I developed tourettes / ticking a few years ago when I was around 32 and I wonder whether it could be related to the psychosis I once had. When I researched sudden onset ticking I couldn’t really find much about it! There hasn’t been a day in past 4 years I’ve not ticked and it is worse than ever.

https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_s...

Curious if you've heard about socially-induced Tourette-like behaviours? There was a HN post about it not too long ago, one of the signs was sudden onset later in life: https://news.ycombinator.com/item?id=33878155

Funny you mention this, because it was only when that story came out that I could even find info about sudden onset Tourette's in people. Mines is the full vocal and movement ticks. But ticks only happen when I get memory flashbacks, which are approximately 50-100 times a day.

I'm not fully convinced here, I bet those long term patients were on antipsychotics nearly all of which have extrapyramidal side effects, pretty identical to negative symptoms.

It’s worth mentioning here that antipsychotics have come a long way since lithium. (Posting from the US with our unfortunate (relative to the developed world) healthcare system.)

There’s a handful of antipsychotics and mood stabilizers that have been developed in the last couple of decades that have had unprecedented success with Schizophrenia and Bipolar Disorder. They typically cost $20,000.00 per year before insurance (mine is $0.00 per year after insurance and a coupon, and they get cheap when their patent expires (the patent-clock is 20 years and starts when development starts)). I get to lead a normal life thanks to my medication, and I have experienced no side effects besides the typical mild brainwashing (totally worth it when compared to the alternative). I have friends on other similar newfangled medication, and they have similarly wonderful results.

Please forgive the Lisp-ish parentheses. I figure it’s halfway acceptable on HN.

> Please forgive the Lisp-ish parentheses. I figure it’s halfway acceptable on HN.

Haha it did make me wander if there was an Emacs HN client with paren mode.

> It’s worth mentioning here that antipsychotics have come a long way since lithium.

It's not really related to your comment which is interesting and useful to hear in of its self.

But Lithium is not a antipsychotic it's a mood stabiliser and remains to this day a good one. It remains to this day the best evidenced for suicide reduction and intractable depression.

Mood stabilizers haven't progressed much (valproate a favoured one is now out for fertile women due to risk of ASD and birth defects).

Antipsychotics have shown astounding progress as you say, the reintroduction of clozapine in the 90, introduction of second generations, then Aripiprazole(as a partial D2 agonist was a warning shot we didn't know as much as we thought), quetiapine (made us reassess what a second generation even means as it has even less D2 affinity), pimavanserin (! No D2 but some 5HT-2a activity) And future like SEP-856(!! What the fuck is TAAR1?!).

Represent astounding progress. Should SEP-856 get a market authorization it'll turn decades of the dopamine hypothesis fully on its head.

I lump the two groups of medications together because I’m under the impression that lithium was the most popular option for schizophrenia/bipolar 50 years ago (typically associated with the diagnoses that result in the need of a mood stabilizer or antipsychotic today). Not to mention depression. Am I missing something here?

I also assumed that lithium would have been responsible for the comment to which I was replying talking about the side effects of the medications. (Lithium is known to significantly alter personality over the long term, yes? (Once again, often worth the alternative.)) The intended use of my comment was to clarify that the side effects of drugs prescribed for schizophrenia/bipolar have calmed down a lot.

You sound knowledgeable, and I’m expressing my curiosity. It’s such a soft science relative to something like cancer that I really have no idea what’s going on (I’m just a code monkey). I’m really not aware of any popular antipsychotics being prescribed 50 years ago, but I’m open to having my ignorance fixed.

Even if you did call my comment useless :(

Oh god so sorry! I meant useful. I found it useful to read of your personal journey.

Regarding Lithium for schizophrenia, I believe it's use only is to manage affective (mood) changes rather than psychosis.

Personality change is very hard to objectively consider. Personalities change with time, so it's harder to compare if a drug will alter someone's personality compared to being untreated for decades in an objective way.

All that said, it's commonly described that people feel different on some medications and I think that has to be accepted. Even if it's hard to objectively measure, and hard to quantify.

We often think of mental illness as distinct from personality (yet we also often see personality disorders as mental illness a paradox).

Of course then we should expect treatments will alter personality.

That said we seem to see personality changes claimed with a number of medications, from antiepileptics to statins used for cholesterol, and beta blockers.

Thanks for the clarification!

Putting people on drugs that disable their cognition and brain function and calling it progressively effective is nothing but a crime to me. Have a good day sir.

Isn't TAAR1 related to some of amphetamine's mechanism of action?

Do you enjoy being on a dopamine antagonist? Are you happy?

It was always my observation that the extrapyrimidal side effects of the meds didn't help but that the negative symptoms - burning out if you like - is also a real thing.

What do you make of the thus-far success of the Soteria Houses/paradigm?

I think the proponents of this method of treatment and practitioners involved would argue that schizophrenia is not a lifelong disease, and true improvement is possible without the standard treatment methodology commonly seen in psychiatric hospitals.

Here are some links of interest that I pulled up in a quick Google search - unfortunately research is lacking and widespread implementation is yet to happen in any meaningful amount outside of Europe -

https://www.psychologytoday.com/us/blog/psychiatry-through-t...

https://www.madinamerica.com/2020/10/original-soteria-member...

https://www.wikiwand.com/en/Soteria_(psychiatric_treatment)#...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632384/

Draw whatever conclusions you would like from those links and further research if you're interested, but here are my 2¢:

A for-profit psychiatric hospital, that is basically a prison (with locked doors, restrictions to personal freedom, restraints, forced medication - a place that strips its patients of rights, with almost no recourse for patients if they are unhappy with their standard of care), is incredibly harmful.

Imagine being released from a psychiatric hospital in the USA and having been told that you will be ill (suffer from schizophrenia) for the rest of your life.

You will have to take (sometimes expensive) medication(s) for the rest of your life (and to never skip a dose or it might cause relapse).

You get hit with an exorbitant bill that you likely can't pay. No concrete changes to your life (besides massive debt) were made by the psychiatrist/therapist/support staff. Your family is still the same, your living situation may be the same or it might have been turned upside down. You probably lost your job if you had one, depending on onset/etc.

I'd feel pretty helpless. I'd also be traumatized by the experience, especially if I were involuntarily hospitalized.

I think our current standard of "care" worsens mental illness - especially delusions and persecution complexes. It makes patients believe that they will never truly be better, unless they constantly "seek help" - taking away any shred of confidence, provides no real-life solutions (operates inside a vacuum), bills an extremely vulnerable person exorbitant amounts of money, and is designed to keep the patient coming back.

Medication can have paradoxical side effects which, depending on severity, can only be rectified under controlled circumstances (hospitalization), and as the OP's link points out, schizophrenia is probably a bit more complicated than simply being caused by genes and so-called chemical imbalances.

I believe trauma, lifestyle, diet/nutrition, environment, physical activity levels, isolation/lack of a support system, and medical problems (like heavy metal poisoning), vitamin deficiencies, bad gut biome/digestive issues/food allergies, and chronic, systemic inflammation are more likely the causative agents to point to (that psychiatrists tend to ignore/downplay in favor of medication above all else for whatever reason).

I think that capitalism and for-profit should never go near the word hospital, especially a hospital that focuses on helping people in crisis.

I think what helped me brake out of too is that I learned to accept (and not fight) the possibility that we are all living in an illusion, and that we are all sharing the same consciousness and that it’s the job of all our senses; eyes, ears, etc to keep us efficiently preoccupied. Maybe I was just struck by philosopher lightening! Haha!

In a way, it gives an aroma of truth to reality is all perspective. It’s fascinating to think that mental models affect the rendering of reality. Language enforces a particular constraint on its own.

Sounds like manic psychosis too. My ex loses touch with consensus reality sometimes when she's manic. It's frightening trying to interact with her and it's like she's not there.

I have been in a similar place with a partner too. It is a terrifying state I have never seen in anyone else before… pure catatonic episodes. But there was a level of extreme paranoia and at times I would be accused of conspiring with an ex (who I didn’t know) to ‘get’ her. This particular relationship that I had was extremely tough and left lasting damage on me - enough for me to avoid any intimate relationship for a few years till i could recover. I hope she is doing better now.

While the parasite is found throughout the world, more than 40 million people in the United States may be infected with the Toxoplasma parasite.

Once a diagnosis of toxoplasmosis is confirmed, you and your health care provider can discuss whether treatment is necessary. In an otherwise healthy person who is not pregnant, treatment usually is not needed. If symptoms occur, they typically go away within a few weeks to months. For pregnant women or persons who have weakened immune systems, medications are available to treat toxoplasmosis.

https://www.cdc.gov/parasites/toxoplasmosis/gen_info/faqs.ht...

Maybe we should make it more of a priority to treat it rather than be all "Meh. Not symptomatic. Moving on."

This! So this. We also need to reestablish “chronic” as a word with only bad connotations; not something that means it’s ok to live with chronic diseases like t1d or x-arthritis’. Solving the overactive immune system will solve an outsized portion of what’s afflicting western populations. Depression, chronic fatigue, any auto immune disorder, etc.

I think the main tangible risk is if you have an autoimmune disorder such as HIV.

Seems like the reason for not treating in general is that human guts are already infested with all sorts of relatively harmless bacteria (and protozoa, etc.). And the drugs to treat toxoplasmosis, which are certain antimalarials and antibiotics, carry some risk. A big risk is that, if you nuke your gut biome with 1-3 antibiotics for everything you get infected with, and they develop resistance which spreads horizontally, it could prevent antibiotics from saving your life when you're infected with something serious.

That being said, if there's a link established between t. gandii infection and suicidality, I'd speculate you'll see lots of pressure from the public health folks for treating all infections.

This is not medical advice and I am not a doctor. I have time to sit in an armchair and argue about toxoplasmosis on a Friday night. Please take that into account.

"Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two."[0] While city life is as complex of a confounding factor as anything, the fact that they found hunter-gatherers have practically no incidence of SZR is interesting. Is the modern megalopolis simply too intense of a stimulus for the minds of the sensitive to handle without splitting into pieces?

[0] https://en.wikipedia.org/wiki/Schizophrenia#Environmental

Does schizophrenia occur more often in people with certain genetic traits? Does the majority of people with such traits live in urban environments, e.g. in highly urbanized countries?

(No idea; just a hypothesis to test.)

More likely to be diagnosed in a city too I would imagine.

Hunter gatherer societies no doubt considered them to be shamans or treated them with psychedelics

I'm bipolar and I'd definitely would be a shaman or prophet. I've got the right balance of intelligence and crazy for it.

Or pushed them off a cliff.

I suspect, if this effect is real, it has more to do with social supports, the size of the social group, and maybe also metaphysical/religious beliefs and attitudes. People who have a worldview like "Demonic possession is real! And no big deal! Happpens to everyone from time to time!" skew non-urban. They may well interact, socially and emotionally speaking, with schizophrenic relatives and community members, in a better and healthier way, than we, in all our enlightenment, do. A case of minor thought disorder, for example, can probably either be aggravated or lessened based on the social response to it. The secular Westerner may not think schizophrenics are demon-possessed, but we sure tend to treat them like they are cursed.

I read an article once about treatment of schizophrenics in an African country. Basically put in a single cage but monitored and treated well. Westerners saw it as barbaric, but the local culture saw them as being possessed in a good or bad way and most recovered in a month and there was a ceremony to welcome them back from their journey. No negative societal MH stigma attached to it.

Medically, not sure about it, but culturally seems more mature than we have.

I think a more likely reason why hunter gatherers don't have aren't prone to schizophrenia (in this model) is that it was evolutionarily bread out of them. Hunter gatherers in the modern world are extremely weird populations that are often under intense selective pressure!

This may be better explained by the Hygiene hypothesis - hunter-gatherers get exposure to all sorts of microbes and parasites early in their life while city-dwellers could be shielded from equivalent exposure. See: https://en.wikipedia.org/wiki/Hygiene_hypothesis

The study directly tackles this question in section 3, including why it is very rare in hunter-gatherer societies.

> We suggest that one reason why the prevalence of psychosis among people with hunter-gatherer and traditional lifestyles is so much lower than in people with contemporary western lifestyles is due to chronic stress and low-grade systemic inflammation caused by western lifestyle.

Why is chronic stress important? It brings impaired immune response and chronic inflammation. This lets a number of parasites through the door, one of which is _Toxoplasma gondii_, the mind-control parasite that causes mice to not fear cats.

> In light of the parasite x genotype x stress model, a probable explanation for why living in cities increases the risk of schizophrenia is increased chronic stress caused by urban living (see Lederbogen et al., 2011). City living is associated with increased amygdala activity and affects the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect, and stress (Lederbogen et al., 2011). Functional magnetic resonance imaging research has shown that city living and urban upbringing are associated with altered neural processing of acute social stress (Lederbogen et al., 2011). There is also substantial evidence indicating that visiting green spaces and being exposed to natural environments reduce psychological stress (Ewert and Chang, 2018).

> Living in cities can increase contact with Toxoplasma gondii through domestic cats because cats have a more limited choice of defecation sites in urban areas (Torrey and Yolken, 2014). Likewise, it is possible that the high prevalence of schizophrenia among people with contemporary western lifestyles compared to hunter-gatherers might be caused by the higher prevalence of domestic cats and diseases associated with them. It is also possible that contemporary western lifestyles and living in cities negatively influence gut health and gut microbiota (Fig. 1). Further evidence for this hypothesis comes from findings showing that people with hunter-gatherer lifestyles have more diverse microbiota than people with contemporary western lifestyles (Sanchez-Quinto et al., 2020, Segata, 2015, Singh et al., 2019, Yatsunenko et al., 2012).

The effect is stronger than that as it scales with population densities. Geoffrey West's works explore this in some detail.

Wonderful!

I've worked in the mental health field for years and when it comes to treating diseases like schiziphreina the go to model has been to give drugs to manage symptoms. There were a bunch of models for what _could_ be happening but there was no solid etiology for what is actually happening.

Gut inflamation along with a bunch of correlations with infections and autoimmune issues have been noted for years. Yet, there hasn't been a foundation setup to truly answer what _IS_ schizophrenia etiologically speaking.

Schiziphrenia is a heart-wrenching disease both for the people suffering from it and for their loved ones. Seeing papers like this give me tremendous hope.

I will rejoice if this leads to effective treatment. Our family has a close relative who is afflicted with it. It's a world of chaos for everyone in their orbit.

As someone formally diagnosed with schizophrenia, I would say the worst parts of it are anhedonia and stigma. Anhedonia means we can just rot in our apartments for days at a time getting nothing accomplished and stigma prevents us from working even when we overcome the mountain that is anhedonia. Honestly, I wouldn’t wish it on my worst enemy.

My brother was diagnosed with same and certainty suffers from anhedonia to this day.

You seriously think the public stigma is one of the "worst" things about it? Almost no one my brother encounters knows about his diagnosis and yet he suffers a lot. I sort of doubt other people's opinions are of primary significance in that, although perhaps his perception of how others see him does seem a bit problem

Think about it: how likely is it for an employer to hire someone who self-discloses schizophrenia? And if you choose not to disclose, how do you explain the gaps in your resume when you were involuntarily committed or recovering from a recurring series of episodes? Stigma still plays a big role, even in today’s society. Edit: And that is to say nothing of the problems you face if you are kicked out of the hospital with no place to go. Schizophrenia is a scary illness, bro.

Hmm. My brother has never had interest in holding a job for too long so it isn't something I think about a ton.

If an employer doesn't want to hire someone who occasionally disappears I understand that and I'm not sure it's stigma.

Anyhow, this is a sensitive topic and thanks for discussing it. It's hard to unfurl and investigate these things. Good luck with your own experience.

I may be atypical because I was able to work in industry for a few years before my formal diagnosis. My illness was exacerbated by the fact that I could no longer bolster my identity with work and achievement, so I have found other ways (meditation, medication, and therapy, mostly) to cope with my symptoms.

Good luck with your brother.

my dad had schizophrenia and he starved himself to death because he thought most food and water was poison. he was estranged from his family and was on the streets off and on, mostly because he was ashamed. he on some level knew he was delusional and was ashamed of it, which you would think would undermine his delusion, but i suppose fear comes first.

I would imagine anosognosia could be worse. I know someone who delayed diagnosis and treatment because they didn't believe anything was wrong with them (although it was obvious to everyone around them)

As an anlogy, consider how hard it would be to convince a random person they have to take diabetes medication if they don't have it. It is the same way convincing a schizophrenic person with anosognosia to take antipsychotic medication.

What you're describing as anhedonia also includes avolition. At least in my case, there are three components that feed back into each other: avolition - that lack of impulse to do ... anything, even when there are strong stimuli; executive dysfunction - even if you're ready to act, a sense of being overwhelmed by choices and unable to put one foot in front of another; and anhedonia - even if you're finally doing something pleasant or productive, there's absolutely no mental reward or lasting sense of accomplishment to build upon. A row-row-row-your-boat of suck as it were.

Okay, this is fascinating.

The fact that “schizophrenia is rare or nonexistent in hunter-gatherer populations” is particularly interesting.

I had no idea this was the case.

Clearly there is much more research to be done, but I feel like the authors are on the right track here.

Similarly interesting:

“The striking difference was that while many of the African and Indian subjects registered predominantly positive experiences with their voices, not one American did. Rather, the U.S. subjects were more likely to report experiences as violent and hateful – and evidence of a sick condition.“

Seems related to how one might associate oneself to perspectives under religion. Vedic adjacent religions seem to cater to having a relationship with many entities of various forms.

My Christian parents thought I was demon-possessed. That was quite helpful.

> It is therefore possible that the behavioral changes induced by Toxoplasma in humans, including suicidality, are a part of its adaptations to increase the probability that our ancestors were eaten by lions or leopards

What the what

I am skeptical that most suicidal people, who may idealize or even follow through on shooting or hanging themselves, would willingly let themselves be eaten by a lion. Fight or flight adrenaline in the face of big cats feels like a likely effective cure for suicidal ideation…

> Normally, a protozoan is not very likely to end up in a cat’s gut because rodents instinctively fear cats. In Toxoplasma-infected rodents, however, the fear of cats disappears (Vyas et al., 2007). The mere smell of a cat normally makes rodents flee, but rodents infected with Toxoplasma experience the smell of cat as sexually attractive (Berdoy et al., 2000, House et al., 2011). This makes them seek out cats, making Toxoplasma-infected rodents more likely to end up as cat food. These rodents still avoid other predators as before (Berdoy et al., 2000, House et al., 2011). The reversal of this innate fear reaction helps the protozoan reach its definitive host, a cat, and to propagate its genes to future generations.

I hear theories like "this parasite has evolved to make it's host want to be eaten by lions" and I instinctually think that's crazy, but then I remember all the way more crazy things that nature does, and it starts to sound reasonable. Thanks for sharing!

Don't Google search "parasitic ant fungus" then.

When I first learned how HIV (and retroviruses) worked, it was the same level of amazement. Like "it splices its own genes into your cells' DNA, and when your cells reproduce, they additionally make copies of the HIV virus" is just something that I would have never thought was real.

I think folks like myself, who became an "amateur epidemiologist" during covid (out of necessity, because of the information vacuum) were shocked to learn all these amazing things we weren't ever told. As an aside, the same is true for everyone who is now an "amateur diplomat" post-invasion and read about realism etc. and well-understood and reasonable explanations for "why the U.S. is always at war" that make it seem so logical. Crazy to think there are so many other fields keeping amazing secrets like this.

Nature is fucking terrifying. Every time I see some zoo program on the telly where "oh we're rehabilitating these endangered rabbits and then we'll release 'em back into the wild where they'll be free and happy". Not sure that's how the rabbits feel about it.

If I were a rabbit in one of these programs I'd feign a limp, hide in the corner, anything I could to avoid being cat or wolf fodder, or getting one of the dozens of tortuous diseases and parasites that infect rabbits in the wild.

Wow, this is amazing, I totally didn't know this.

Makes the case for this happening in humans seem more plausible.

Like my sibling comment said, thanks for sharing!

I'd think that likely. Ideation is easy. Actually pulling the trigger is difficult. Survival instincts are strong.

In the paper, they hypothesize that the route of transmission would have been big cats scavenging human remains after suicide.

Of course this, like all evolutionary psychology, is basically unknowable and highly susceptible to just-so story telling

T. gandii and its lifecycle are not in the scope of evolutionary psychology, though. It actually reproduces (sexually) in cat gut and the (cysts of the) host animal actually need to be eaten by a cat (or other host). I agree that EP can lead to dangerous, political, and moralistic ways of thinking.

But the idea that parasites have lifecycles and incentive to survive and reproduce does not deserve such criticism. It's mainstream biology. Toxoplasmosis is a real thing that really affects behavior in wild mice. Read it on Wikipedia.

> https://en.m.wikipedia.org/wiki/Toxoplasma_gondii

>Toxoplasma gondii infection in mice lowers general anxiety, increases explorative behaviors and surprisingly increases a general loss of aversion to predators (without selectivity toward cats).

Whether toxoplasmosis causes suicidal ideation in humans is less clear and more speculative, as you argued. I agree. But the mode of parasite transmission, assuming a psychological effect exists in humans, would indeed be Alice being eaten by a cat and then Bob touching cat shit.

Here is a diagram of the known lifecycle: https://en.m.wikipedia.org/wiki/Toxoplasma_gondii#/media/Fil...

Actually you might be surprised [1] [2] [3]

[1] https://www.independent.co.uk/travel/africa/lion-kills-man-g...

[2] https://www.telegraphindia.com/west-bengal/calcutta/alipore-...

[3] https://www.dailymail.co.uk/news/article-3602819/Naked-man-j...

>The young man broke into the enclosure, took off his clothes and jumped into the middle, horrifying other visitors who witnessed the attack.
>Once inside, the lions reportedly immediately pounced on him and began to 'play' with him.
>At this point, zookeepers intervened in the attack and shot the two lions in order to save his life.
>The director of the zoo, Alejandra Montalva, said: 'We believe that this person entered as a visitor and paid for his ticket.
>The zoo director said she was 'deeply affected' by the deaths of the two lions, a male and a female.
>One witness said the man was 'shouting things about Jesus'. They continued: 'He was screaming religious things.'
>According to the news channel, the suicide note that was found inside his clothes made allusions to the apocalypse as being a reason for his attempt to take his life.

>He added: 'He suffered several injuries and trauma to the head and the pelvic area. 'We have high hopes that will recover and that will be fine.'

How is this guy the victim here? What about the lions?

[Edit: retracted dumb speculation]

That sounds like the bacteria that makes ants hang off of leaves to get eaten by predators to spread the parasite. Similar to that cat pee bacteria thing.

Does cat ownership cause toxoplasmosis, or does toxoplasmosis make you want to be around cats?

There aren’t many people that have more than 2-3 dogs. You can’t say the same for cat people.

Come to Georgia. Quite a few people have 10-15 dogs. Even in suburban neighborhoods. I've subjectively seen more "pack of dogs" type people than "cat ladies".

It's a cultural thing; I'm not arguing there's some kind of "dog toxoplasmosis". Wikipedia says the evidence for (feline) toxoplasmosis causing crazy cat ladies is not definitive, either. https://en.m.wikipedia.org/wiki/Toxoplasmosis#Society_and_cu...

Wasn't schizophrenia identified as basically off-by-one (multiple?) error of the deletion algorithm in the brain that is garbage collecting more (glial?) cells in a row than needed during teenage years? And "overclocking" glial cells by adding large quantities of Niacin/NAD+ partially alleviates those symptoms?

No.

It's a neurological disorder and is more complicated than a one off bit, especially when it involved the entire CNS because it's associated with the brain. Many of these issues can't be cured as easy as flipping a bit.

I mean if it is an unrecoverable loss of glial cells during puberty (AFAIK most diagnoses start during that time) then nobody would be able to "flip the bit" back anyway. As glial cells feed and protect neurons, their lack will likely have unrepairable consequences, unless the remaining ones are somewhat boosted to partially cover the functionality of the missing ones. I am interested in this topic because a cousin has inherited it from her father's family (super intelligent people) and their family life is destroyed from it. They basically just manage symptoms with regular crazy periods when one medication ceases to function and they have to switch to another one that might not work.

Most diagnoses for schizophrenia are in the early twenties for men and late twenties for women, so not really in puberty/teenage years. I don't believe anyone can be diagnosed before adulthood if they're not exhibiting exceptionally extreme symptoms either.

At the very least there seem to be 10s of causes of schizophrenia and just as many different manifestations of it. Similar to cancer or depression in that regard.

Yes, so another umbrella diagnosis that can have 100s different reasons with the same outward symptoms. Like some people with pellagra exhibiting the same symptoms but when their nutrition improves long-term, they get completely cured from it. I only remember some Harvard/Stanford or similar article in the past five years about deleted cells because of a genetic defect akin to off-by-one error in programs.

https://www.sciencedirect.com/science/article/pii/S003331827...

This seems consistent with Chris Palmer's hypothesis, that mental disorders are metabolic disorders of the brain, discussed in his new book Brain Energy[0]. He's done lots of podcast interviews[1], if you don't want to read the book.

[0] https://www.chrispalmermd.com/ [1] https://www.listennotes.com/search/?q=chris%20palmer%20md&so...

In what way is this consistent? The authors describe toxoplasma infection forming cysts in the brain as a result of immune response. The cysts then release neurotransmitters, primarily dopamine and glutamate, which presumably causes the cognitive symptoms of schizophrenia.

What does that have to do with metabolism?

The idea that toxoplasmosis is a contributing factor to mental illness is decades old. This paper is merely an incremental restatement of that hypothesis. The abstract says, "Instead of just alleviating symptoms with drugs, the parasite x genotype x stress model emphasizes that schizophrenia treatment should focus on detecting and treating possible underlying microbial infection(s), neuroinflammation, gut dysbiosis, and chronic stress."

Chris Palmer's treatment emphasizes reduction of inflammation and dysbiosis via dietary means. This hypothesis is not limited to treatment of schizophrenia, but also other mental illness, such as bipolar disorder. The following two recent podcasts are illuminating.

https://www.psychiatrypodcast.com/psychiatry-psychotherapy-p...

https://www.rickhanson.net/being-well-podcast-evolving-our-a...

I recommend the book The Schizophrenias - Ours to conquer by Carl C. Pfeiffer. It divides schizophrenia into several phenotypes that have metabolic causations.

I used to have manic episodes for my whole life, but managed without medication. After I fixed my histamine oversupply in the body around march(by cutting folic acid and histamine-rich foods from my diet and taking L-methylfolate supplements), I haven't had another episode.

I used to have allergies and crazy food cravings for sugar and other unhealthy stuff because of the histamine issues which are gone now. This phenotype is called histadelia.

Then there is histapenia, where you have too much copper accumulated in your body and it can’t get rid of them unless you take higher doses of zinc and mangan(and a chelator to avoid complications). Folate and histamine levels are too low.

Overall B-Vitamins are pretty important. If you need them its way higher doses than RDA(b3, b6, b2)

Thyroid problems can be involved in schizophrenia, aswell as gluten intolerance.

Also recommend the books by Dr. Abram Hoffer.

Is it safe for children to live with cats?

Is it safe to live?

Interesting stuff. I often wonder if all humans are just a little schizophrenic, and only when the condition develops do things like auditory hallucinations occur.

One model might be several different people running around in a maze, only able to communicate with each other by shouting over the walls. The brain is the maze, but the fractioning of the individual's identity (internal schizms) is what creates the internal illusion of disassociated individuals. This might even develop into neural schizms, different parts of the brain not actually being able to communicate well with other parts of the brain.

I don't know if that model is even vaguely correct, but it would explain auditory hallucinations, as one part of the brain might only be able to communicate with another by utilizing the auditory channel.

Here's an interesting 1993 paper on the subject, lays out the background:

Diagnosis and Classification of Schizophrenia

available via title search at:

https://scholar.archive.org/

I will have to sit down and read this over the weekend.

But I'm a bit put off by its focus on evolutionary origins. It's prevalence is circa 1% (claimed in article at 0.76%), that's too rare to really gun for an evolutionary basis like you do for cystic fibrosis or sickle cell.

Circa 1/30 carries the CF gene which shows Mendelian inheritance and so we week a evolutionary basis.

Dozens of potential mechanisms described, with none uniquely convincing IMHO. One interesting suggestion is the group splitting hypothesis:

> The group-splitting hypothesis of schizophrenia (Stevens and Price, 2000) posits that proliferating tribal communities must eventually split to maintain optimum numbers. According to this hypothesis, schizotypal traits in certain prominent individuals may be advantageous to ensure survival of the offshoot group. These prominent individuals could use paranoia, delusions, religious themes, and neologisms to fraction disaffected groups and to seed new cultures.

If it’s the case that it’s driven by some organism/parasite/virus, it’s interesting that there’s a prevalence for certain age groups to get it over others (or rather, it is much more rare to get after certain ages). Maybe some combination of genetic factors or comorbidities at play as well.

Would love to learn more. Especially how this relates to other disorders eg OCD, bipolar disorder, etc.

I'm reminded of the story I've head (I believe via a podcast, though I cannot presently find the source) on syphilis as a mental-health issue.

The upshot is that cases of syphilitic psychopathy were treated as psychiatric illnesses, that is, strictly disorders of the brain, and there was a substantial network of mental health asylums for housing and treatment of patients.

Successful treatment of the infectious disease syphilis all but eliminated this class of mental health disease, and is among the very few instances of successful management at a public-health level of a category of mental illness. The fact that the psychological disease was entirely based on physical (and specifically infectious) medicine is highly notable.

The mental health sector continues to perform poorly at looking beyond strictly psychological aspects of mental health, and in particular has placed a probably unjustified emphasis on psychotropic medication as opposed to other interventions --- not just of potential infectious-disease causes as with syphilis and posited here for schizophrenia, but of environmental and social factors.

I also suspect that psychiatric / psychological conditions are best considered, similarly to cancer, as a set of symptom clusters, which may have markedly distinct etiologies. Traditional psych focuses more on the symptoms than the etiologies.

It's as if we had an infectious medicine based on, say, runny noses or laboured breathing, without considering cause. (There are areas of physical medicine which do resemble this, and others, such as trauma treatments, in which root cause is relatively insignificant concerning treatment, in at least many cases.)

For the benefit of Future Readers (most likely Future Me), I've tracked down the episode.

It was the 28 October 2019 CBC Ideas episode "What Psychiatrists Still Don't Know About Mental Illness", in which Anne Harrington discusses her book, Mind Fixers. The case of syphilitic psychosis, "general paralysis of the insane", is discussed in chapter 1.

Podcast: <https://www.cbc.ca/radio/ideas/what-psychiatrists-still-don-...>

Book: <https://bookshop.org/p/books/mind-fixers-psychiatry-s-troubl...> <https://libgen.rs/book/index.php?md5=A04307D5ABF5A467E9B1D1F...>

There are of course many other authors discussing syphilus and mental health, including Thomas Insell, Healing: Our Path from Mental Illness to Mental Health, discussed on the Ezra Klein podcast (and elsewhere).

Podcast/Transcript: <https://www.nytimes.com/2022/07/22/podcasts/transcript-ezra-...>

Book: <https://bookshop.org/p/books/healing-our-path-from-mental-il...>

If you're interested in mental health, check out Pyroluria, which has been found to co-exist with many mental health conditions, making them worse.

Is it possible that the same root causes also trigger cluster-b disorders?

Parasite based, interesting.

Half joking but the shift from understanding szr as an intrinsic psychological condition versus being causally related to parasites remind me hilariously of the midichlorians reveal in star wars.

I think we'll probably see a lot of this kind of synthesis as our ability to model grows stronger.

Seeing yourself as a collection of billions of separate but symbiotic, sometimes competing organisms rather than as one coherent one is a big paradigm shift which will likely result in a lot of fruitful theories and hopefully eventually treatments for disease and illness.

Crucially, we're getting to a place where we can model some of this and then directly attack several other pieces which were inaccessible to us before due to sheer amount of complexity.

Also similar to the Epstein-Barr virus link to MS

So Ivermectin for everyone?

I was under the impression that ivermectin wouldn't affect a protozoa.

And even if it did, it wouldnt pass the blood brain barrier so it would be useless here.

[I am not a doctor and dont know what im talking]

Per this article protozoa could be affected:

https://pubmed.ncbi.nlm.nih.gov/8918027/

One would have to administer it in early stages before it passes BBB. Pity it got such a bad rap because Zapp Brannigan mentioned it (despite winning a Nobel Prize).

> Schizophrenia (SZR) is rare or nonexistent in hunter-gatherer populations.

People really bend over backwards to insist that schizophrenia is not iatrogenic.

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