THE JOYFUL REDUCTION OF UNCERTAINTY

Treating The Prodrome

A prodrome is an early stage of a condition that might have different symptoms than the full-blown version. In psychiatry, the prodrome of schizophrenia is the few-months-to-few-years period when a person is just starting to develop schizophrenia and is acting a little bit strange while still having some insight into their condition.

There’s a big push to treat schizophrenia prodrome as a critical period for intervention. Multiple studies have suggested that even though schizophrenia itself is a permanent condition which can be controlled but never cured, treating the prodrome aggressively enough can prevent full schizophrenia from ever developing at all. Advocates of this view compare it to detecting early-stage cancers, or getting prompt treatment for a developing stroke, or any of the million other examples from medicine of how you can get much better results by catching a disease very early before it has time to do damage.

These models conceptualize psychosis as “toxic” – not just unpleasant in and of itself, but damaging the brain while it’s happening. They focus on a statistic called Duration of Untreated Psychosis. The longer the DUP, the more chance psychosis has had to damage the patient before the fire gets put out and further damage is prevented. Under this model it’s vitally important to put people who seem to be getting a little bit schizophrenic on medications as soon as possible.

There has been a lot of work on this theory, but not a lot of light has been shed. Observational studies testing whether duration of untreated psychosis correlates with poor outcome mostly find it does a little bit, but there’s a lot of potential confounding – maybe lower-class uneducated people take longer to see a psychiatrist, or maybe people who are especially psychotic are especially bad at recognizing they are psychotic. The relevant studies try their hardest to control for these factors, but remember that this is harder than you think. The randomized controlled trials of what happens if you intervene earlier in psychosis tend to do very badly and rarely show any benefit, but randomly intervening earlier in psychosis is hard, especially if you also need an ethics board’s permission to keep a control group of other people who you are not going to intervene early on. Overall I could go either way on this.

Previously I was leaning toward “probably not relevant”, just because it’s too convenient. There is a lot of debate about how aggressively to treat schizophrenia, with mainstream psychiatry (and their friends the pharma companies) coming down on the side of “more aggressively”, while other people point out that antipsychotics have lots of side effects and their long-term effects (both how well they work long-term, and what negative effects they have long-term) are poorly understood. These people tend to come up with kind of wild theories about how long-term antipsychotics hypersensitize you and make you worse. I don’t currently find these very credible, but I’m also skeptical of things that are too convenient to the mainstream narrative, like “unless you treat every case of schizophrenia right away you are exposing patients to toxicity, and every second you fail to give the drugs makes them irreversibly worse forever!” And I know a bunch of people whose level of psychosis hovers at “mild” and has continued to do so for decades without the lack of treatment making it much worse.

After learning more about the biology of schizophrenia, I’ve become more willing to credit the DUP model. I can’t give great sources for this, because I’ve lost some of them, but this Friston paper, this Fletcher & Frith paper, and Surfing Uncertainty all kind of point to the same model of why untreated schizophrenia might get worse with time.

In their system, schizophrenia starts with aberrant prediction errors; the brain becomes incorrectly surprised by some sense-data. Maybe a fly buzzes by, and all of a sudden the brain shouts “WHOA! I WASN’T EXPECTING THAT! THAT CHANGES EVERYTHING!” Your brain shifts its resources to coming up with a theory of the world that explains why that fly buzzing by is so important – or perhaps which maximizes its ability to explain that particular fly at the cost of everything else.

Talk to early-stage schizophrenics, and their narrative sounds a lot like this. They’ll say something like “A fly buzzed by, and I knew somehow it was very significant. It must be a sign from God. Maybe that I should fly away from my current life.” Then you’ll tell them that’s dumb, and they’ll blink and say “Yeah, I guess it is kind of dumb, now that you mention it” and continue living a somewhat normal life.

Or they’ll say “I was wondering if I should go to the store, and then a Nike ad came on that said JUST DO IT. I knew that was somehow significant to my situation, so I figured Nike must be reading my mind and sending me messages to the TV.” Then you’ll remind them that that can’t happen, and even though it seemed so interesting that Nike sent the ad at that exact moment, they’ll back down.

But even sane people change their beliefs more in response to more evidence. If a friend stepped on my foot, I would think nothing of it. If she did it twice, I might be a little concerned. If she did it fifty times, I would have to reevaluate my belief that she was my friend. Each piece of evidence chips away at my comfortable normal belief that people don’t deliberately step on my feet – and eventually, I shift.

The same process happens as schizophrenia continues. One fly buzzing by with cosmic significance can perhaps be dismissed. But suppose the next day, a raindrop lands on your head, and there’s another aberrant prediction error burst. Was the raindrop a sign from God? The evidence against is that this is still dumb; the evidence for is that you had both the fly and the raindrop, so your theory that God is sending you signs starts looking a little stronger. I’m not talking about this on the conscious level, where the obvious conclusion is “guess I have schizophrenia”. I’m talking about the pre-conscious inferential machinery, which does its own mechanical thing and tells the conscious mind what to think.

As schizophrenics encounter more and more strange things, they (rationally) alter their high-level beliefs further and further. They start believing that God often sends signs to people. They start believing that the TV often talks especially to them. They start believing that there is a conspiracy. The more aberrant events they’re forced to explain, the more they abandon their sane views about the world (which are doing a terrible job of predicting all the strange things happening to them) and adopt psychotic ones.

But since their new worldview (God often sends signs) gives a high prior on various events being signs from God, they’ll be more willing to interpret even minor coincidences as signs, and so end up in a nasty feedback loop. From the Frith and Fletcher paper:

Ultimately, someone with schizophrenia will need to develop a set of beliefs that must account for a great deal of strange and sometimes contradictory data. Very commonly they come to believe that they are being persecuted: delusions of persecution are one of the most striking and common of the positive symptoms of schizophrenia, and the cause of a great deal of suffering. If one imagines trying to make some sense of a world that has become strange and inconsistent, pregnant with sinister meaning and messages, the sensible conclusion might well be that one is being deliberately deceived. This belief might also require certain other changes in the patient’s view of the world. They may have to abandon a succession of models and even whole classes of models.

A few paragraphs later, they expand their theory to the negative symptoms of schizophrenia. That is: advanced-stage schizophrenics tend to end up in a depressed-like state where they rarely do anything or care about anything. The authors say:

Further, although we have deliberately ignored negative symptoms, it is interesting to consider whether this model might have relevance for this extremely incapacitating feature of schizophrenia. We speculate that this deficit could indeed be ultimately responsible for the amotivational, asocial, akinetic state that is characteristic of negative symptoms. After all, a world in which sensory data are noisy and unreliable might lead to a state in which decisions are difficult and actions seem fruitless. We can only speculate on whether the same fundamental deficit could account for both positive and negative features of schizophrenia but, if it could, we suggest that it would be more profound in the case of negative features, and this increased severity might be invoked to account for the strange motor disturbances (collectively known as catatonia) that can be such a striking feature of the negative syndrome.

I think what they are saying is that, as the world becomes even more random and confusing, the brain very slowly adjusts its highest level parameters. It concludes, on a level much deeper than consciousness, that the world does not make sense, that it’s not really useful to act because it’s impossible to predict the consequences of actions, and that it’s not worth drawing on prior knowledge because anything could happen at any time. It gets a sort of learned helplessness about cognition, where since it never works it’s not even worth trying. The onslaught of random evidence slowly twists the highest-level beliefs into whatever form best explains random evidence (usually: that there’s a conspiracy to do random things), and twists the fundamental parameters into a form where they expect evidence to be mostly random and aren’t going to really care about it one way or the other.

Antipsychotics treat the positive symptoms of schizophrenia – the hallucinations and delusions – pretty well. But they don’t treat the negative symptoms much at all (except, of course, clozapine). Plausibly, their antidopaminergic effect prevents the spikes of aberrant prediction error, so that the onslaught of weird coincidences stops and things only seem about as relevant as they really are.

But if your brain has already spent years twisting itself into a shape determined by random coincidences, antipsychotics aren’t going to do anything for that. It’s not even obvious that a few years of evidence working normally will twist it back; if your brain has adopted the hyperprior of “evidence never works, stop trying to respond to it”, it’s hard to see how evidence could convince it otherwise.

This theory fits the “duration of untreated psychosis” model very well. The longer you’re psychotic, with weird prediction errors popping up everywhere, the more thoroughly your brain is going to shift from its normal mode of evidence-processing to whatever mode of evidence-processing best suits receiving lots of random data. If you start antipsychotics as soon as the prediction errors start, you’ll have a few weird thoughts about how a buzzing fly might have been a sign from God, but then the weirdness will stop and you’ll end up okay. If you start antipsychotics after ten years of this kind of stuff, your brain will already have concluded that the world only makes sense in the context of a magic-wielding conspiracy plus also normal logic doesn’t work, and the sudden cessation of new weirdness won’t change that.

The Frith and Fletcher paper also tipped me off to this excellent first-person account by former-schizophrenic-turned psychologist Peter Chadwick:

At this time, a powerful idea of reference also overcame me from a television episode of Colombo and impulsively I decided to write letters to friends and colleagues about “this terrible persecution.” It was a deadly mistake. After a few replies of the “we’ve not heard anything” variety, my subsequent (increasingly overwrought) letters, all of them long, were not answered. But nothing stimulates paranoia better than no feedback, and once you have conceived a delusion, something is bound to happen to confirm it. When phrases from the radio echoed phrases I had used in those very letters, it was “obvious” that the communications had been passed on to radio and then television personnel with the intent of influencing and mocking me. After all betrayal was what I was used to, why should not it be carrying on now? It seemed sensible. So much for my bonding with society. It was totally gone. I was alone and now trusted no one (if indeed my capacity to trust people [particularly after school] had ever been very high).

The unfortunate tirade of coincidences that shifted my mentality from sane to totally insane has been described more fully in a previous offering. From a meaningless life, a relationship with the world was reconstructed by me that was spectacularly meaningful and portentous even if it was horrific. Two typical days from this episode I have recalled as best I could and also published previously. The whole experience was so bizarre it is as if imprinted in my psyche in what could be called “floodlit memory” fashion. Out of the coincidences picked up on, on radio and television, coupled with overheard snatches of conversation in the street, it was “clear” to me that the media torment, orchestrated as inferred at the time by what I came to call “The Organization,” had one simple message: “Change or die!” Tellingly my mother (by then deceased) had had a fairly similar attitude. It even crossed my (increasingly loosely associated) mind that she had had some hand in all this from beyond the grave […]

As my delusional system expanded and elaborated, it was as if I was not “thinking the delusion,” the delusion was “thinking me!” I was totally enslaved by the belief system. Almost anything at all happening around me seemed at least “relevant” and became, as Piaget would say, “assimilated” to it. Another way of putting things was that confirmation bias was massively amplified, everything confirmed and fitted the delusion, nothing discredited it. Indeed, the very capacity to notice and think of refutatory data and ideas was completely gone. Confirmation bias was as if “galloping,” and I could not stop it.

As coincidences jogged and jolted me in this passive, vehicular state into the “realization” that my death was imminent, it was time to listen out for how the suicide act should be committed. “He has to do it by bus then?!” a man coincidentally shouted to another man in the office where I had taken an accounts job (in fact about a delivery but “of course” I knew that was just a cover story). “Yes!” came back the reply. This was indeed how my life was to end because the remark was made as if in reply to the very thoughts I was having at that moment. Obviously, The Organization knew my very thoughts.

Two days later, I threw myself under the wheels of a double decker, London bus on “New King’s Road” in Fulham, West London, to where I had just moved. In trying to explain “why all this was happening” my delusional system had taken a religious turn. The religious element, that all this torment was willed not only by my mother and transvestophobic scandal-mongerers but by God Himself for my “perverted Satanic ways,” was realized in the personal symbolism of this suicide. New King’s Road obviously was “the road of the New King” (Jesus), and my suicide would thrust “the old king” (Satan) out of me and Jesus would return to the world to rule. I then would be cast into Outer Darkness fighting Satan all the way. The monumental, world-saving grandiosity of this lamentable act was a far cry from my totally irrelevant, penniless, and peripheral existence in Hackney a few months before. In my own bizarre way, I obviously had moved up in the world. Now, I was not an outcast from it. I was saving the world in a very lofty manner. Medical authorities at Charing Cross Hospital in London where I was taken by ambulance, initially, of course, to orthopedics, fairly quickly recognized my psychotic state. Antipsychotic drugs were injected by a nurse on doctors’ advice, and eventually, I made a full physical and mental recovery.

Chadwick never got too far along; he had all the weird coincidences, he was starting to get beliefs that explained them, but he never got to a point where he shifted his fundamental concepts or beliefs about logic in an irreversible way. As far as I know he’s been on antipsychotics consistently since then, and has escaped with no worse consequences than becoming a psychology professor. I am not sure whether things would have gone worse for him without the medications, but I think it’s a possibility we have to consider.

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103 Responses to Treating The Prodrome

  1. Incurian says:

    In Psych 101 they tell you to expect that you’ll start to believe you have every disorder mentioned, but not to worry because stop being stupid. I assume Scott eschewed this warning because he’s secretly trying to undermine my confidence on behalf of the global conspiracy to delay my inevitable rise to heavenly power.

    • b_jonas says:

      I don’t study psychology. Yet I come across descriptions of all sorts of psychological disorders on the internet, and I also get told that many descriptions psychological disorders (and in fact of some physiological disorders too) are too convincing, and you often start to believe that they apply to you. I have to actively consider that bias whenever I’m thinking that I have some disorder. Yet I also shouldn’t completely ignore those thoughts, because recognising a disorder early and getting help about it can significantly improve my quality of life or life expectancy.

      Before the internet, about the only psychological disorder I heard anything about was autism, and even that only from the Rain Man movie. And at that time, nobody had told me yet that many descriptions of psychological disorders are too convincing. So obviously, back then I was wondering if I was autistic. Around 2004 (yes, that’s technically after the dawn of the internet), I asked my psychologist whether I was autistic, and mentioned the Rain Man. She also did not tell me that such descriptions of psychological disorders can be too convincing. (She did convince me in a different way that I was probably not autistic. She could do that because I knew that she obviously knew more about autism than I did.)

      • baconbits9 says:

        If some psychiatric disorders are subroutines running amok you would expect an typical person to notice bits and pieces of them in themselves. We have probably evolved to double check that rustle in the bushes, or to interpret a series of cues as “is someone or something following me?”, so it wouldn’t be surprising if everyone had, at some point, the feeling of being watched/followed without evidence or confirmation.

      • evolutiontheorist says:

        What’s it called when a list of symptoms or traits is so vague that basically everyone sits there nodding along, going “yeah, that’s me!”? Like with astrological horoscopes.

        I think there’s something similar with the definitions of a lot of these disorders. They have to compress a variety of different psychiatrists’ experiences with a variety of different people into a list of traits that can be compared against new potential patients, and there’s obviously going to be some data loss in the process. Psychiatrists also want the descriptions to be vague enough to cover people who clearly have problems, but whose condition is slightly different from previous patients’.

        So if you’re a psychiatrist who has actually worked with 100s of autistics, you probably have a pretty definite mental model of what “autism” looks like and can say with confidence “yes, you have it” or “no, you really don’t, despite superficially matching some of the things on that list.” But if you’re just reading the list without any experience, it’s rather like reading that “Tauruses are always ready for a good time with their friends but cautious about people they don’t like” and thinking “Yeah, that’s me.”

        • Joseph Greenwood says:

          Is this what you are talking about?

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

        • Simon_Jester says:

          I always figured it was a case where there’s a normal level where a given ‘symptom’ is just a personality trait most people have, and then it becomes pathology when it gets cranked up to eleven on the dial.

          I mean, most people have had the experience of some random coincidence really hitting them with a metaphorically palpable ‘thud.’ Like, you’re looking across the room at an attractive person and HOLY SHIT your favorite song just came on the sound system. Or you’re looking out at some beautiful scene of a storm that just passed by clearing the air and there’s rainbows and HOLY SHIT is that a double rainbow with a lightning bolt going through it.

          And most of us have, at one time or another, felt that something which was objectively concidence was in fact important; human beings do this to each other’s interpersonal behavior ALL THE TIME. See for reference Scott’s theory in another post that human social communication occupies this weird valley of being deliberately obfuscated for deniability purposes, while trying to be juuuust barely clear enough to communicate the needed messages.

          But then the thing is, schizophrenics have this all the time, way more often than normal, to the point where the normal self-check and stabilization processes built into the way our minds work can’t compensate.

          It’s like, one of the symptoms of a broken elbow is that your elbow hurts. As I write this, my elbow hurts a little. I could go “oh god, I have that symptom of a broken elbow, and I DID fall a few feet the other day, what if my elbow’s broken?” Checking off a list of symptoms naively I might believe that, if I had no prior experience of what broken bones are like.

          But an expert, or even a regular person with experience with broken bones, would say something else. They’d say “Ahaha, no. What you feel right now is mild discomfort. When someone really has a broken elbow, it expresses itself as a whole different level of pain than this.”

          I think a lot of people who self-diagnose with psychiatric problems (or who other-diagnose people as being narcissists/sociopaths/etc) are doing this on some level- mistaking milder versions of the symptom that are basically personality traits, for the symptom itself… Which is understandable if most psychiatric disorders are in some way an exaggeration or derangement of a natural personality trait or psychological process.

          • Nancy Lebovitz says:

            A couple of things from memory, so they might not be accurate.

            From a book I’ve got somewhere, which claims that a lot of what look like psychiatric problems are actually sensory processing disorders. A man who had what looked like paranoia– he thought trees were coming at him– actually had a visual problem with distance. I don’t know, this doesn’t sound like typical paranoia.

            Susan Haden Elgin wrote in her newsletter about how she assumed that she would be able to check plausibility if she hallucinated, but when she was undergoing withdrawal from a steroid, she started seeing a CIA communication center in her hospital room, and completely believed it at the time.

            This makes me wonder about how people generally trust what they’re experiencing when they dream, and whether that mechanism is in play when awake in some mental illnesses.

  2. volfyd says:

    Not a lot to add, but both my parents were paranoid schizophrenic and the model described here matches my understanding of the disease progression.

  3. Fluffy Buffalo says:

    Do occultists suffer from self-induced schizophrenia?

    • Scott Alexander says:

      Cf Jung’s comment to James Joyce on his schizophrenic daughter: “You’re swimming, she’s drowning.”

      • Fluffy Buffalo says:

        You mean, they HAVE something like self-induced schizophrenia, but they do not SUFFER from it?

        Does that offer approaches to get this stuff under control?

        • andrewducker says:

          People see connections between things all the time. We make assumptions and draw conclusions based on the evidence we have, which frequently isn’t enough to *know*, but we need a working hypothesis.

          Turning that up a bit leads to interesting creativity, and the ability to come up with outlandish science fiction novels. Turn it up too far and everything feels like it’s connected to everything else.

          • John Cody says:

            I’m worried that I am developing psychosis. I’m trying to divert it into a sci-fi novel. Better that I come up with fun sections of narrative than dangerous nonsense about the world around me.

          • Freddie deBoer says:

            If you’re serious, let me please suggest that diverting psychosis into a sci-fi novel is a very unwise strategy and that you’d be much better off visiting a doctor.

          • rummah says:

            I suppose this might explain Finnegan’s Wake. At least it would account for the bizarre literary style James Joyce employed.

          • Joseph Greenwood says:

            This is not a coincidence because nothing is ever a coincidence.

          • CherryGarciaMillionaire says:

            This is not a coincidence because nothing is ever a coincidence.

            Littlewood’s Law would say otherwise:

            Littlewood defines a miracle as an exceptional event of special significance occurring at a frequency of one in a million. He assumes that during the hours in which a human is awake and alert, a human will see or hear one “event” per second, which may be either exceptional or unexceptional. Additionally, Littlewood supposes that a human is alert for about eight hours per day.

            As a result, a human will in 35 days have experienced under these suppositions about one million events. Accepting this definition of a miracle, one can expect to observe one miraculous event for every 35 days’ time, on average–and therefore, according to this reasoning, seemingly miraculous events are actually commonplace.

            Even “meaningful coincidences” are just what happens when you roll the dice often enough.

          • rlms says:

            @CherryGarciaMillionaire
            Lurk (at the Scott’s other work) moar.

        • Seppo says:

          Does that offer approaches to get this stuff under control?

          I think so. I already had a high prior on “schizophrenia is the modern Western form of shamanic sickness” and this post has raised it a bit.

          Briefly, in cultures where it’s still socially acceptable to become a professional wizard/shaman/etc., the lore is that some people are destined to do so, and if those people fail to commit to the appropriate training, they will develop a crippling mental disorder. The details vary by culture, but a typical progression is that you get depressed, then start complaining about demons chasing you, then start avoiding people, then stop eating or speaking in intelligible words, then die. Some psychologists (e.g. Jung, above) have thought that this sort of thing sounds suspiciously similar to schizophrenia.

          It’s also generally claimed that the sickness can be ended completely at any point in that progression just by going to your local shaman and getting yourself initiated and trained.

          So. The basic magical approach to things like cosmically significant buzzing flies is:
          – sure, God sends messages this way all the time and you should listen to him
          – but so do demons, and you should definitely not listen to them
          – also sometimes it’s really seriously just your imagination
          – here’s a variety of tests you can use to help figure out which is which
          – more importantly, here are some rituals that will scare most of the demons away

          The end result is usually a person who still does odd things for odd reasons a lot of the time but is basically a happy, functioning member of society.

          The “schizophrenia = shamanic sickness” theory should imply that schizophrenic symptoms can be treated with traditional banishing rituals, and I’d love it if someone did an actual RCT to find out for sure. I expect trying to get it funded would be hilarious, though: “You’re saying you want to test whether schizophrenia can be cured by… drawing pentagrams in the air with a stick while chanting in fake Hebrew? Are you sure you aren’t schizophrenic???” (But I mean, come on, fight crazy with crazy, right?)

          • The Nybbler says:

            “You’re saying you want to test whether schizophrenia can be cured by… drawing pentagrams in the air with a stick while chanting in fake Hebrew? Are you sure you aren’t schizophrenic???”

            Hey, no way, that would be unethical. We’ll use real Hebrew.

          • Simon_Jester says:

            Well, I mean, the shamanic rituals would basically be a high-powered placebo treatment. Now, this isn’t wrong as such, because hell, whatever works!

            The problem is twofold.

            One, its effectiveness will depend entirely on belief, and damaging belief in the power of the treatment will greatly reduce its effect. By contrast, antipsychotic drugs work whether you believe in them or not, although I’m sure they work better if you expect them to work.

            Since many people no longer really believe in systems of magic, you may run into problems selling the “you’re actually a shaman and the spirits are talking to you” narrative to someone who’s coming down with schizophrenia.

            Because that narrative has to compete with other ones better aligned to the spirit of our times like “the CIA and the television company are talking to you,” because we KNOW those are real. 😛

            Two, the traditional “become a wizard” career path for incipient schizophrenics only works if society at large is actually willing to subsidize wizards as a form of social welfare for schizophrenics. Like, if you’re not willing to regularly go to your tea-leaf-reader who “uses” their schizophrenia to ritualistically tell you what tea leaves mean for your future, then you’re undermining this system.

            There are probably more efficient ways for us to subsidize the ongoing health and welfare of schizophrenic people, especially since many if not most people no longer actually believe in shamans, again. Most of us won’t really want to rely on them as the arbiters of religious custom and our destinies.

          • Scott Alexander says:

            I don’t know if Seppo is claiming shamanism is placebo. I think he might be claiming that shamanism is a belief system that explains schizophrenic experience, in a condition that (if the above theory is true) is exacerbated by having experiences that can’t fit into a sane belief system and so involve abandoning systematic belief entirely.

            That is, schizophrenics have to invent their own belief system in order to explain their experiences, often they do a bad job, but cultural evolution did a better job and invented one that explains all random experience so well that you don’t have to sputter around abandoning cognitive function as your brain fails to weave events into a coherent outside world.

          • albatross11 says:

            Damn, is *that* gonna be an entertaining IRB meeting!

          • Ashley Yakeley says:

            You should really watch Dr. Robert Sapolsky’s lecture about Biological Underpinnings of Religiosity. Thesis: it’s specifically subclinical versions of particular mental illnesses that give rise to various forms of religiosity, and are probably evolutionarily adaptive, whereas the full-blown mental illnesses are maladaptive.

            Sapolsky identifies three in particular:

            1. Schizotypalism as subclincal schizophrenia, which resembles shamanism. The important thing from an evolutionary standpoint is that shamans hear voices at the right time, and thus have a well-respected role in their societies.

            2. Subclinical OCD, which gives rise to ritualism. Sapolsky points out ritualistic rules in Judaism, Christianity, Islam as well as Hindu Brahmanism, with the top four categories of behaviour shared with OCD: cleansing, food preparation, entering/leaving significant religious places, numerology.

            3. Temporal-lobe personality as subclinical temporal-lobe epilepsy. These folks tend towards religious visions, and tend to write obsessively, with an obsessive interest in religious & philiosophical subjects.

          • Fluffy Buffalo says:

            First, thank you for a really deep and informative answer!

            Second: there’s one context where I could imagine a clinical trial like the one you suggest actually going through. You know that the Catholic Church still trains and employs exorcists? And they might be open enough to scientific approaches to allow a study of the efficacy of exorcism.
            Any volunteers? :-/

    • Ketil says:

      It sounds like one could induce schizophrenia in someone through gaslighting?

      • JRG says:

        Not gaslighting exactly, but a hostile and persecutory social environment can definitely increase the risk of psychosis. There is solid research that is pretty well replicated that first generation immigrants are at much higher risk for psychosis in a way that is independent of family history and is not easily attributable to characteristics they had before immigrating. A lot of the effect seems to be driven by immigrants who are dark-skinned who move to countries where the majority of the population are not dark-skinned, which suggests to me that the diathesis of the individual is not the only relevant factor here.

        • Quixote says:

          Is there a significant sample size in the other direction? If so it would be interesting to compare to try to extract if the result is a feature of unfamiliar environment or a feature of particular environments. I know a lot of Western expats work oversees for a while, but the fact that they tend to selected for overseas executive work selects for high income and high functioning, so it might not be well sample matched.

        • Paul Torek says:

          Moreover, war refugees have a higher risk than economically driven migrants. Source: my wife, a psychologist.

  4. vaticidalprophet says:

    Dammit, Scott, why did you have to pick psychiatry and not a more ethical specialty, like prescribing opiates to children?

    I really don’t mean to be an asshole. I like most of your posts. But I read things like this, and I wonder how different the world would be if people studied chlorpromazine for a bit longer before deciding it was such a good idea.

    My first question is: What are you defining as the ‘prodrome’, here? Your example of a prodromal patient is someone so psychotic he threw himself in front of a bus to fight Satan in the Shadow Realm. By this definition, the vast majority of people diagnosed with psychosis are going to need some reclassification. Does ‘prodromal’ mean ‘psychotic, but also smart’? Despite what papers on limited samples imply, there are smart people with long-term psychosis. Which leads to…

    Why does everyone in this conversation (and I have been following this conversation and all its papers for a long, long time) ignore the existence of papers on long-term untreated psychosis, or the actual present-day existence of people with long-term untreated psychosis who are sometimes willing to answer questions? We have a few papers on pre-chlorpromazine outcomes; they imply about two-thirds of patients made a full enough functional recovery to leave the institution within a couple years, in an era with little in the way of social safety nets or tolerance for weirdness. Some of the remaining one-third leave in longer-term followups, but others stick around. How many of them would today with those supports is an uncertain question. We also have people right here, right now, in this timeslice, with extremely long ‘DUPs’ — yes, there are neuroleptic-naive people, including neuroleptic-naive middle-class or over smart people, in 2018 — and people who chose to stop neuroleptics after taking them for some time (or were one of the eighty-odd people in psychiatric history who got randomized to the zero-neuroleptics arm of a study). What does it look like when you’re schizophrenic for five or ten or twenty years and don’t take neuroleptics? Well, why don’t you find out?

    Also, who the hell is making a model of SZ as a disease process and IGNORING NEGATIVE SYMPTOMS? Negative symptoms ARE the disease! They’re the disabling part! They’re the ones that screw you over! You can function in plenty of high-intensity environments being delusional, you can’t being unable to get out of bed! You can’t treat negative symptoms as “well, we IGNORED them because they DON’T MATTER, but here’s what would happen if we’re right, which we, a bunch of people who clearly have no functioning model of this neurotype, definitely are”! Hell, do they know there are forms of SZ typified by negative symptoms, or did that get put in the Forbidden Knowledge box when the DSM-5 came out? Hebephrenia is a lot worse than psychosis, shouldn’t we be focusing on early treatment for that? The one long-term DUP person I know who is truly severely disabled, by which I mean she’s around the 75th percentile of functioning for people undergoing treatment, is 90% negative symptoms.

    • Scott Alexander says:

      Usually prodrome is defined as “with some insight”. I agree Chadwick doesn’t really fit and I was confusing him with a different account I almost posted. I’ve changed the post a bit to reflect this, although I think there is an important sense in which he hasn’t reached the stage where he gets negative symptoms or clangs or formal thought disorder or things like that yet.

      I don’t think everyone ignores these papers; I linked Moncrieff, who I consider one of the better people discussing this. My impression is that the orthodox position is that 30% of people with schizophrenia will recover spontaneously or at least end up with nothing worse than a few delusions occasionally. That having been said, the claims that pre-antipsychotics people did better are mostly false; remember Kraepelin called the disease “dementia praecox” because it seemed like the irreversible decline into dementia only faster. Studies of schizophrenics in Third World countries that don’t have antipsychotics tend to show similarly bad results. The most recent study I’ve seen on this is very confusing and has a lot of bad features, but does show people treated with antipsychotics doing better than people who are not over their long-term followup (they say 20 years, but most cases were less than that), which accords with similar previous studies.

      My guess is that some people get the deterioration into their brain rearranging their concepts to fit the random data, and so end up with formal thought disorders, word salad, etc, and other people don’t and will be mostly stable their whole lives. I don’t know to what degree this is normal human variation vs. grouping two different disorders into one label.

      I think there’s like a 20% chance that antipsychotics will turn out to have been a terrible idea making everything much worse, and maybe another 30% chance that they will turn out on net to have been bad because we basically understood the paradigm right but were miscalculating benefits vs. risks. But I don’t think it’s obvious, and this post is about one of the things that shifts me away from that position.

      I think the Frith model of schizophrenia is elegant precisely because it does explain negative symptoms so well. I think it’s silly of them to downplay that as much as they do.

      • vaticidalprophet says:

        Thank you for approaching me on good faith — I tried not to be too harsh about the topic, but it’s one I have *really strong feelings on* and can’t really ignore the cognitive dissonance when reading you.

        >I’ve changed the post a bit to reflect this, although I think there is an important sense in which he hasn’t reached the stage where he gets negative symptoms or clangs or things like that yet.

        It’s more reasonable, but in what sense are things like negative symptoms inherently a late-stage affliction? I suspect a lot of the interest in them as late-stage comes from mixing up negative symptoms with neuroleptic side-effects, because in my experience as a long-term DUP person who interacts with a lot of people with very little exposure to neuroleptics compared to what’d be expected of their neurotypes, true negative symptoms unrelated to drugs pop up fairly early. This might be more a factor that I was adolescent-onset and know a lot of young people; I’m not sure how old Chadwick was during his experience, and the association between age and negative symptoms is well-known. They also might resolve over time in some of the no/low-exposure population (they did for me, do in Harrow and Wunderink), which isn’t really an observation in high-exposure populations (presumably the symptoms alleviate right around when the side effects kick in).

        Thought disorder is a weird topic, and probably not much can be gathered on it from modern-day DUP people because we tend to only get away with it by being neurodivergent at baseline (and so having high baseline rates), but I do get what you’re getting at there.

        >My impression is that the orthodox position is that 30% of people with schizophrenia will recover spontaneously or at least end up with nothing worse than a few delusions occasionally.

        I get the same impression, which is interesting given that the actual patient population doesn’t reflect this — recall the trouble Elyn Saks went through finding participants for her high-functioning SZ study, and especially in terms of being turned away by psychiatrists or quoting claims that someone who regains functioning was probably misdiagnosed (!). This has the obvious confounder that recovered people might not have much psychiatric contact anymore, which works if the recovery is unrelated to neuroleptics/defined such that you can quit taking them after doing so, but I’ve also seen plenty of definitions of ‘recovery’ phrased as No, You Have To Keep Taking The Meds Forever. And then you’d be in the system, so they’d have a record of you and should by all rights know HFSZ is a thing — it’s all kinds of confusing, really.

        >That having been said, the claims that pre-antipsychotics people did better are mostly false; remember Kraepelin called the disease “dementia praecox” because it seemed like the irreversible decline into dementia only faster

        I’m familiar with Kraepelin’s perspective, yes. I’m not sure it’s the only applicable framework. There are certainly cultures throughout history (including today) that conceptualized SZ in a different way and don’t seem to have records of e.g. their shamans all becoming nonfunctional a few years after appointment. I’ve met high-DUP people who read as constantly decaying, but they don’t seem like the rule and they’re still doing better than a lot of treated patients. I probably read as constantly decaying for a couple years there, and I’m doing infinitely better on every axis than the early-onset SZ profile. I do have a high enough baseline IQ to probably be a non-representative example, but I’m also unsure how non-representative a male with poor premorbid functioning can really be there.

        >Studies of schizophrenics in Third World countries that don’t have antipsychotics tend to show similarly bad results.

        Can you provide some support for this claim? It doesn’t match my own reading, but I’m interested.

        >most recent study

        It has a nice big sample size, but everything else is awful. The median followup for the largest two groups is 13-15 *months*. The ‘outcomes’ are only death or hospitalization — not, say, *anything related to day-to-day functioning*. While death and revolving door syndrome are both serious QOL impairments, being unemployable or dropping out of high school to be a NEET for four years when you’re third-sigma intelligent are *also* serious QOL impairments. I get you said it has ‘a lot of bad features’, but I’d call this less ‘lots of bad features’ and more ‘essentially worthless for anything past replicating the relapse studies’.

        Also, the injection-as-proxy-for-poor-compliance part interested me, because I read plenty of by-psychiatrists-for-psychiatrists booklets implying injections are actually a great alternative to pills that patients often pick by choice, but I’m not sure how much of that is real, how much is damage control, and how much is Big Pharma trying to sell more risperidone depot. What are your observations there?

        >I think there’s like a 20% chance that antipsychotics will turn out to have been a terrible idea making everything much worse, and maybe another 30% chance that they will turn out on net to have been bad because we basically understood the paradigm right but were miscalculating benefits vs. risks.

        Do you practice in the way that having a 50/50 chance of thinking neuroleptics were a bad idea would imply?

        • b_jonas says:

          > injections are actually a great alternative to pills that patients often pick by choice

          Oh yes. At least if it’s administered by reasonably skilled medical workers (as opposed to eg. a long term self-managed therapy at home), I’d choose injections or IV infusions in favor of most other forms of administering drugs almost any time, unless the needle would go near my eyes. I know there’s a lot of individual variation here of course.

          But I don’t know how useful proxy that is in this study.

        • JRG says:

          So a thing that gets missed out on in these discussions is that schizophrenia is not a coherent entity in and of itself. It is a collection of symptoms that often go together and that were selected to increase interrater reliability (i.e., so two different clinicians would both agree on the label to use to describe a given person) rather than because there was a strong belief that that collection was a thing that had an independent existence in the world. Latent class analyses of symptom patterns (supplemented sometimes by extensive interviews of relatives to figure what symptoms they have experienced) consistently demonstrates several different behavioral endophenotypes subsumed within the umbrella of schizophrenia, although the details are not entirely consistent from paper to paper. One thing that does tend to come up frequently is that there is a distinction between people who have really florid positive symptoms that tend to a)respond dramatically to medications and b) don’t seem to have a significant decrement in function longitudinally on the one hand, and people on the other hand who a) have much less extensive positive symptoms b) don’t benefit all that much from medications and c) decline in functioning pretty steadily. Again, the picture is more complicated than this, but this leaps out at you when you read the literature.

          My experience working with first-episode psychosis is that the higher-functioning folks who have had these experiences and gotten better tend to employ a “sealed-over” recovery style, in which they deal with the understandably traumatic memories of what happened to them by wanting to pretend it did not happen and certainly to avoid discussing it or dwelling on it if at all possible. We have in our society this idea of what being “schizophrenic” means, and it is not a pretty picture at all, so why would you want to identify with that if you could pass? This probably explains the difficulty locating that 30%.

          It is also the case that psychosis =! SCZ, but many clinicians are not that experienced with psychosis, so a lot of people who have had other kinds of psychotic disorders wind up with the label regardless. There are many other systems of nosology when it comes to psychotic disorders that draw very different distinctions; Karl Leonhard’s work on cycloid psychoses is fascinating in this regard, and this is a concept used in Scandinavian psychiatry and certainly describes some of the people I’ve worked with. Cycloid psychosis is a very different experience from classical Kraeplinian dementia praecox!

          I would say careful cross-cultural studies tend to find that while yes, some cultures have much more room for acknowledging and finding value in some kinds of psychotic experiences, almost all to date have some concept of “madness” or “insanity” that is not seen as a magical or spiritual experience but that also tends to have in common, at minimum, some burden of hallucinations/delusions and disorganization.

          I have met people who genuinely prefer IM medications (often with residual concerns about food contamination/poisoning) but most people need to be cajoled into doing this. There is an idea in our field that LAIs increase adherence, but this is shaky and certainly does not seem to apply in the long-run to the set of folks who are going through frequent hospitalizations. I think they are helpful for folks who need assertive community treatment approaches and also for people whose cognitive deficits make it really hard for them to remember to take pills regularly and also to get them from the pharmacy in a timely fashion.

          Ultimately, “you need to take pills forever” is a terrible message for someone with first-episode psychosis. Specialists in this area generally don’t say sh*t like this. Current thinking is much more along the lines of “lowest-effective dose for 18-24 months, then discuss taper if client is interested [some people aren’t]”. This should be supplemented by intensive psychoeducation, family therapy, vocational/occupational rehab, case management services, and psychosis-specific therapies. These therapies, by the way, all tend to emphasize learning to accept experiences and function despite symptoms rather than trying to obliterate them.

          I could ramble about this topic for many hours, but I must say I am very curious about your personal experiences and how your interactions with the treatment system went.

        • Scott Alexander says:

          “It’s more reasonable, but in what sense are things like negative symptoms inherently a late-stage affliction? I suspect a lot of the interest in them as late-stage comes from mixing up negative symptoms with neuroleptic side-effects, because in my experience as a long-term DUP person who interacts with a lot of people with very little exposure to neuroleptics compared to what’d be expected of their neurotypes, true negative symptoms unrelated to drugs pop up fairly early. This might be more a factor that I was adolescent-onset and know a lot of young people; I’m not sure how old Chadwick was during his experience, and the association between age and negative symptoms is well-known. They also might resolve over time in some of the no/low-exposure population (they did for me, do in Harrow and Wunderink), which isn’t really an observation in high-exposure populations (presumably the symptoms alleviate right around when the side effects kick in).”

          This is possible. The few prodromes I’ve seen have been mostly positive symptoms, but I don’t have much experience and I haven’t read the literature at a level where I’m sure I’m missing the bias you mention.

          “Thought disorder is a weird topic, and probably not much can be gathered on it from modern-day DUP people because we tend to only get away with it by being neurodivergent at baseline (and so having high baseline rates), but I do get what you’re getting at there.”

          Not sure I’m entirely understanding your point here. My impression of thought disorder is that it is a very serious condition that doesn’t look like any kind of baseline neurodivergence. Wikipedia gives the example of someone being asked why people comb their hair and answering “Because it makes a twirl in life, my box is broken help me blue elephant. Isn’t lettuce brave? I like electrons, hello please!” This fits my experience with some thought-disordered people. I can think of contrived scenarios where you could mistake ordinary neurodivergence for a severe thought disorder, but it doesn’t seem like a likely common mistake. Milder cases are surely more confuse-with-something-else-able but I still think there’s a core of definite weird and unique stuff with that label. I think of this as something that happens after the brain has completely rearranged its categories and priors in a random or perverse way.

          “I get the same impression, which is interesting given that the actual patient population doesn’t reflect this — recall the trouble Elyn Saks went through finding participants for her high-functioning SZ study, and especially in terms of being turned away by psychiatrists or quoting claims that someone who regains functioning was probably misdiagnosed (!). This has the obvious confounder that recovered people might not have much psychiatric contact anymore, which works if the recovery is unrelated to neuroleptics/defined such that you can quit taking them after doing so, but I’ve also seen plenty of definitions of ‘recovery’ phrased as No, You Have To Keep Taking The Meds Forever. And then you’d be in the system, so they’d have a record of you and should by all rights know HFSZ is a thing — it’s all kinds of confusing, really.”

          I think of this in the context of the studies I mentioned in Against Against Autism Cures only 4% of autistic people are able to hold down a job. This tells you at least as much about who gets included in autism studies as about disease processes. I’m not sure I would say it’s wrong – it might just mean some psychiatrists doing this study define autism much more strictly than anyone else – but it will certainly lead you astray if you plug it into the popular definition of autism. I’m not sure how many studies of schizophrenia are like this too.

          “I’m familiar with Kraepelin’s perspective, yes. I’m not sure it’s the only applicable framework. There are certainly cultures throughout history (including today) that conceptualized SZ in a different way and don’t seem to have records of e.g. their shamans all becoming nonfunctional a few years after appointment.”

          This is maybe outlandish and I am not sure what to make of it, but a lot of sources say there were no documented cases of anything resembling schizophrenia before about 1850, and Kraepelin was the first person to invent the diagnosis because he was in the first generation of psychiatrists to observe the syndrome. The small amount of work I have put in to see if this is right have mostly agreed that it is. There have been psychotic people forever, but the “classic” schizophrenia course is mostly post-1850. IF it were post-1950 it would be a slam dunk to blame it on the drugs. As it is, it seems possible that some novel pathogen was involved? Idk, this is a really far-out there claim. I’m just mentioning it because I’m not sure how relevant ancient shamans were to anything.

          “Can you provide some support for this claim? It doesn’t match my own reading, but I’m interested.”

          See Torrey’s hostile review of Whitaker.

          “I get you said it has ‘a lot of bad features’, but I’d call this less ‘lots of bad features’ and more ‘essentially worthless for anything past replicating the relapse studies’.”

          I agree it’s awful, but I’m not sure there are any comparable studies that are better? When studies and anecdotes are both awful, I try to synthesize them as best I can and then give the results low confidence, and this is the awful study I’m adding the awful anecdotal evidence to get my low-confidence belief that antipsychotics are not net harmful long-term.

          “Do you practice in the way that having a 50/50 chance of thinking neuroleptics were a bad idea would imply?”

          I practice in a low-acuity outpatient clinic that very rarely gets schizophrenics. I only have two schizophrenic patients. One is on antipsychotics and the other isn’t (though I have recommended them to him based on specific features of his case I think even people who are often against antipsychotics would agree merit them; he has always declined). So yeah, I’m maintaining a perfect 50/50 ratio 😛

          • Nancy Lebovitz says:

            I just realized that your sample of schizophrenic talk shows that words and grammar are intact– it’s something like a Markov chain.

            It just seems like a hint about what isn’t working and what is working.

          • JRG says:

            Re: negative symptoms appearing early, some of the most striking first episode folks I have encountered were extremely negative, e.g. spent a year in their room from which they would emerge every 90 minutes to ask for cigarettes but doing nothing else and otherwise had four responde to all questions, “yes”, “no”, “I’m fine”, “tomorrow”.

            Additionally, the Risk+Decline prodromal subtype tends to be heavy on the negative symptoms. When they do transition DUP tends to be longer because obviously they are unlikely to be seeking treatment spontaneously and it takes a while for family or friends to agree that something is very wrong.

        • vaticidalprophet says:

          I swear I’ll make a more effortposty response eventually, but on thought disorder:

          Thought disorder occurs in neurotypes that aren’t SZ. Some of them are related to SZ, such as Multiple Complex Developmental Disorder, the schizophrenia-autism missing link that would’ve changed the world of ASD diagnosis if the DSM-IV committee didn’t switch it out for Asperger’s at the last moment. Others are less clearly related, like…normal autism. See e.g. A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders (van der Gaag et al, 2005). This isn’t word salad or severe FTD, but it’s thought disorder regardless.

          I experienced thought disorder both before and after crossing over at…overall similar severity, actually. I had some way more prominent thought disorder at the peak of my first episode, and a few more severe incidents a few months ago, including one in the SSC Discord server where I’d come to the conclusion gender dysphoria was caused by thought insertion and was attempting to explain this to a perplexed audience. But MCDD is not quite ARMS, and being a member of the ‘never normal’ subgroup changes the game a little.

    • JRG says:

      Specialists think of the prodrome these days as one of three clinically high-risk syndromes for the most part. The exact criteria are not set in stone yet so I will instead describe the gestalt of these.

      1. Attenuated Psychotic Syndrome – for a relatively long period of time, someone has many perceptual and cognitive experiences that resemble hallucinations or delusions, but are not fully-formed, lack conviction, are still subject to reality-testing, and can be challenged (maybe with mild prompting) by the person experiencing them.

      2. Brief Psychotic Syndrome – someone has classic positive symptoms, for short periods of time (less than a day typically), repeatedly over a significant stretch of time.

      3. Functional Decline + Risk State – someone who has a first-degree relative with a hx of a severe mental illness (generally bipolar I or a psychotic disorder) OR who has previously met criteria for Schizotypal Personality Disorder (ugh, such a gross way of talking about personality structure, but that’s a different rant) AND who has experienced significant functional academic, social, or occupational decline over the past year. These last one are the folks who tend to go on to be more negative earlier on in the course of things.

      These syndromes, depending on the center, have a transition rate to full-blown psychosis somewhere between 15-30%. So obviously most of these people will not become schizophrenic! Note though that this rate is at least an order of magnitude higher than in gen pop.

      There are formalized testing instruments for evaluating these high risk syndromes (Structured Interview for Psychotic Symptoms is the gold-standard) so it is less vague than my description likely makes it seem.

      As to why negative symptoms don’t get talked about as much – psychiatrists are human and don’t like to see our clients suffer and it makes us feel like bad doctors when they have crippling symptoms that we don’t know how to address or help them with. So we start focusing on what we can often treat, for better or for worse. also, positive symptoms tend to be the ones that get people with psychotic experiences into trouble with family/the legal system so there is a lot of external pressure to make sure they are tamped down.

      Are the pre-chloropromazine papers you are talking about from the US? I would be exceptionally cautious in accepting a diagnosis of schizophrenia in this country at face value if it was formulated prior to the late 70s as there was a period of time when American psychiatrists diagnosed everyone with schizophrenia if they had ever failed to reality-test in any way. Hell, Marsha Linehan spent a year in a psychiatric hospital and got repeated ECT because she was diagnosed with “pseudoneurotic schizophrenia”.

      • vaticidalprophet says:

        I appreciate your listing of the disparate experiences that get lumped into the ARMS for people who wouldn’t previously be aware of them — but I’ve probably read a fairly similar number of publications in this field to you, knowing you’re someone who actually works in it. Hell, I was reading several last night. This is not a coincidence. My ‘what the hell is the prodrome?’ doesn’t regard what the concept theoretically refers to, but rather the bizarre places people draw the line between ‘attenuated’ and ‘florid’ psychosis.

        The most inexplicable part is, I was probably schizophrenic in reverse. I define myself as having crossed over around 15/16 because that was when I fell headfirst into things and later became nonfunctional, dropped out, etc., but in practice I was incapable of reality-testing for a long, long time. Now nearly half a decade on I have a very complex and attenuated relationship with reality, but it is actually a relationship. I’d be able to sneak in as any other high-risk MCDD kid in the local youth psychosis program if I didn’t have the inconvenience of already being crazy. (Corollary of “LET’S LOWER THE DUP”: young, functioning-ish people with lengthy DUPs who don’t want to lie about everything anymore fall through the cracks.) This is Not Supposed To Happen, because how can someone with the neurotype at all, let alone the ~severe treatment-resistant early onset form~, go through years of brainrotting and come out the other side better off?

        Ahahaha the Cluster A personality disorders. When I was in the process of crossing over, I had a girlfriend who was much, much older than me and ended up in psych prison over circumstances unnecessary to get into, and came out with an STPD diagnosis. Her first reaction was “hey, that’s the thing you have”. I loudly and constantly denied any resemblance to the diagnostic criteria, even though at age 11 I’d found it and gone “oh, that’s my non-autism thing”, because some bizarre reason about her not being cool enough for me to have it. She then gave me her diagnostic checklist, on which I got the highest score possible. Then I explained that STPD was just pathologizing eccentricity anyway, so none of this mattered.

        >As to why negative symptoms don’t get talked about as much – psychiatrists are human and don’t like to see our clients suffer and it makes us feel like bad doctors when they have crippling symptoms that we don’t know how to address or help them with.

        I’m not knocking the impulse. People do what they think they have to do. Problem is, the end result is a massive mountain of human suffering for very little gain.

        Like…the thing that’s helped me the most with my executive dysfunction is stimulants. Amphetamines. That’s the best treatment for any SZ symptom I’ve ever encountered. Consider the optics of trying to propose this in literally any mainstream psychiatric context.

        >I would be exceptionally cautious in accepting a diagnosis of schizophrenia in this country at face value if it was formulated prior to the late 70s

        Ah, but the neuroleptic era began well before the late 70s. I also understand what you’re getting across here — but how is it so much more relevant to the patients released from the asylum on their own merits than it is to those released with a prescription?

        • JRG says:

          >Ah, but the neuroleptic era began well before the late 70s. I also understand what you’re getting across here — but how is it so much more relevant to the patients released from the asylum on their own merits than it is to those released with a prescription?

          The era of “everything is schizophrenia” started with the rise of the analysts in the US, which was really underway by the late 30s. So you’re right, neuroleptics started being used widely in the early 60s in the US. My point was more that if the outcome studies from the 50s are looking at a “schizophrenia” diagnosis and seeing what happens longitudinally, you are capturing a lot of people who would never get that diagnosis today, such as people with borderline personality disorder, OCD, PTSD [which didn’t even exist as a diagnosis!], etc.

          >I’m not knocking the impulse. People do what they think they have to do. Problem is, the end result is a massive mountain of human suffering for very little gain.

          I find treatment trajectory studies really interesting. If you look at most samples carefully, you will find that about 30% of people put on dopamine antagonists have essentially no response and get zero benefit out of these. About 50% of people get some kind of clinical response but definitely not any kind of remission, and any reduction in symptoms occurs over a relatively long period of time (months). About 10% of people have a really dramatic response to neuroleptics and remit very quickly. I would love to know how to predict those dramatic responders in advance, but clinically the course is very much like lithium-responsive bipolar I – someone goes from being incredibly impaired to being totally fine in a week or two. This is the kind of person who had 8 hospitalizations and was on whopping doses of various LAIs until they met 10 mg of Zyprexa in 1998 and 20 years later they own their own home, have a professional job, grandkids frolicking in their yard, the works. This dramatic response probably drives a lot of the separation from placebo you see in neuroleptic trials.

          Clozapine is a different story but can work wonders and people for whom it is effective tend to be fans of it. True story – most OP psychiatry clinics have a no-show rate between 30-40%, so only about 60% of the time does someone on your schedule actually show up for their appointment. Our clozapine clinic has a 95% attendance rate. It’s kind of amazing.

          At the end of the day I tend to agree with you more than I disagree – to the extent that increased DUP hurts outcomes I think it has a lot more to do with the systematic and extensive burning of bridges and occupational/social/academic decline.

          >The most inexplicable part is, I was probably schizophrenic in reverse. I define myself as having crossed over around 15/16 because that was when I fell headfirst into things and later became nonfunctional, dropped out, etc., but in practice I was incapable of reality-testing for a long, long time. Now nearly half a decade on I have a very complex and attenuated relationship with reality, but it is actually a relationship. I’d be able to sneak in as any other high-risk MCDD kid in the local youth psychosis program if I didn’t have the inconvenience of already being crazy. (Corollary of “LET’S LOWER THE DUP”: young, functioning-ish people with lengthy DUPs who don’t want to lie about everything anymore fall through the cracks.) This is Not Supposed To Happen, because how can someone with the neurotype at all, let alone the ~severe treatment-resistant early onset form~, go through years of brainrotting and come out the other side better off?

          It’s unusual, but it’s not the first time I’ve heard of someone having this experience. Confused about the point about lying re: DUPs, though.

          >Ahahaha the Cluster A personality disorders. When I was in the process of crossing over, I had a girlfriend who was much, much older than me and ended up in psych prison over circumstances unnecessary to get into, and came out with an STPD diagnosis. Her first reaction was “hey, that’s the thing you have”. I loudly and constantly denied any resemblance to the diagnostic criteria, even though at age 11 I’d found it and gone “oh, that’s my non-autism thing”, because some bizarre attenuated reason about her not being cool enough for me to have it. She then gave me her diagnostic checklist, on which I got the highest score possible. Then I explained that STPD was just pathologizing eccentricity anyway, so none of this mattered.

          As I said, personality “disorders” are a whole other rant, but there does seem to be an association between a certain way that people’s reactions and relationships to other people are organized that is predictive of the possibility of more serious impairment down the road. I don’t know that you need to pathologize it exactly but it warrants recognizing as a clinical entity, some people experience a lot of impairment and distress behind it, and we unfortunately have to call it a disease to get paid for trying to provide any help to people who want it.

          >Like…the thing that’s helped me the most with my executive dysfunction is stimulants. Amphetamines. That’s the best treatment for any SZ symptom I’ve ever encountered. Consider the optics of trying to propose this in literally any mainstream psychiatric context.

          This does make me think SZ is possibly a poor fit as a category for your experience, because lots of folks who more clearly fit in the SZ box decompensate dramatically with stimulants. Not trying to discount your experience of your own self, though.

          • vaticidalprophet says:

            I plan to make more effortposty replies soon, but on the final stimulant note: this is actually a thing that has worked for SZ people who are more central examples of the neurotype than I am. See A systematic review of psychostimulant treatment of negative symptoms of schizophrenia: challenges and therapeutic opportunities (Lindenmayer et al, 2013), accessible for people without institutional connections through all the normal grey-market piracy sites. It’s the difference between smoking meth (a bad idea regardless of your neurotype) and taking unprescribed ‘ADHD meds’. There’s a recognized slight increase in positive symptoms, but I…don’t prioritize this as an issue.

          • JRG says:

            Thanks for the paper, I do plan to read this thoroughly. You make a good point that chronic meth use (especially IV) and much, much smaller doses of amphetamine salts are different animals. The former case can lead to symptoms lasting for literally years but again these are very high doses. I think stimulants are vastly over-used and at the same time under-used in psychiatry; on the adult side, unfortunately, antisocial/late-stage addiction folks tend to quickly fill the schedule of anyone known to be open to stimulants and most prescribers have had the experience of being deceived about this so a lot of people are leery about using them.

            Interestingly and possibly relevant to this I remember reading a Swedish registry study that suggested stimulants in normal, medical doses do not seem to increase the risk of mania in bipolar I, at least in people already on lithium/some other maintenance therapy.

          • vaticidalprophet says:

            On the ‘DUP and lying’ note — a really common cause of having a very long DUP is:

            1. Knowing roughly what the psychiatric term for your experience is
            2. Having an extremely strong bias against being diagnosed with that, like (my case) if you’re under 18 and have baseline disabilities and every reason to think you’ll be forced to take drugs you absolutely do not want to take
            3. As a result, whenever you have to interact with the mental health system for whatever reason (and you will, because you are obviously crazy), lying about everything

            I had really, really obvious problems, especially by the time I had crossed over for real and dropped out of school/walked in the middle of the street because I didn’t care about not getting hit by cars/freaked out when anyone touched me/made desperate /r/suicidewatch posts asking when this was going to end/etc. But, strictly speaking, if I didn’t go around telling people their souls were being eaten by the Cabal, I could pass as someone who ‘only’ had profound nonfunctional depression. (I didn’t and don’t have any affective problems, but disclosing that was obviously a stupid idea because there aren’t many other non-psychotic causes for that level of impairment.) I had no interest in taking neuroleptics or being labelled as permanently mentally ill, so I never said anything. I was going to therapy for unrelated reasons and never said anything, which at a certain point meant I was pretty much silent and eventually was strongly recommended to take SSRIs on the “holy shit, I’ve never seen anyone half as depressed as you who wasn’t on them” axis.

            So I took sertraline for a couple months, the iatrogenic hypomania was lots of fun, I quit it when I realized I was at a point where I’d have to take them forever if I stayed on. I then slowly recovered over the next several years and am now attending university only a couple years off schedule.

            I’m now an adult with the adult ability to be the captain of my soul, who’s at least kind of adjacent to NT-passing and clearly not a danger to myself or others, and can interact with psychiatry on my own terms. I’ve opened up about my experiences in the last couple years to the local youth mental health services, who also have an early psychosis program. The consistent response is “Yep, that is definitely psychosis, and it doesn’t have any affective or NOS traits so it’s pretty clear what’s going on there, and also there’s absolutely nothing we can do for you because you aren’t first-episode”.

      • JRG says:

        Re: being unable to get early psychosis services, this is an unfortunate consequence of SAMHSA pouring grant money into this area. This had been great for having specialist services available at all, and especially for having things like non-pharmacological treatments/supports that insurance would never pay for.

        Downside is of course that there are fairly specific conditions imposed on the resulting service lines.

        Out of curiosity vaticidalprophet , how do you feel the mental health system could help you best, if at all?

        • vaticidalprophet says:

          I don’t live in the US. I live in Australia, where in theory the clinical guidelines explicitly include me (I’m 3a or 3b, depending on how strictly you define relapse). This of course just means we have a slightly different source of capricious mostly-government funding, but what else am I supposed to do, manage all of this by myself? (To be fair, I’m infinitely better at it than my new/current therapist. I should probably talk to Headspace about that.)

          What do I want from the system?

          I want to not be talked down to — I’ve accepted that I’m both smarter than almost anyone I’ll meet in it and know more about psychology than them, and also that this combination is something most people will encounter once in a career if ever, so it’s fair for them to be weirded out by it, but my best clinical relationships have been with people who are interested in it and applying both our knowledge to helping me not fail at absolutely everything. I know I’m an outlier, and most people experiencing what I experience (both wrt developmental disability and psychosis) have a very different cognitive skillset, and by definition the system has to be built around them. But I know when people are modelling me as something I’m not. This is the root of a lot of my problems with it, like my strong dislike for my current therapist (and the realization of how lucky I am not to run into any before who are insecure about it) and my inability to access true educational/vocational support.

          And from there — I want a system built around functional recovery and educational/vocational achievement, that in turn doesn’t make the assumption before that ‘functional recovery’ means doing things I’d be horrified to have learn I’d fallen to the point of pre-episode. Or, for that matter, things I couldn’t do pre-episode — twice-exceptional kids are weird. Basically, I don’t want the Elyn Saks ‘are you sure you’re better off at Yale than as a cashier?’ conversation. This is a problem I’m especially afraid of running into, given that I’m a high school dropout on welfare and that doesn’t quite signal my actual abilities.

          I am not capable of working any of the jobs available to most high school dropouts, which is why I’m now going to university to do a double major and do complex research that I’m very capable of — go figure. But I don’t know how I’m actually going to do when I get there, and I have real reason to worry about how well my functional recovery actually went, so I want to be able to know that when I arrive in a new city at the largest and one of the most prestigious universities in the country, I have the educational support I need to not fall into a vat of executive dysfunction and die. The only thing I’m truly bitter about psychosis-wise is being a 20 year old university first-year instead of a 17 year old one. It’s probably for the best in the long run, I doubt 17 year old me could have convinced his parents to let him move interstate, but it hurts my profoundly gifted twice-exceptional kid soul. And it’s because I fell into a vat of executive dysfunction and died, and I really don’t want to repeat that, and I’m not sure I can avoid repeating it at anything short of ‘lives in case manager’s spare room’.

          Also, I tend to be profoundly socially isolated, because when you have one disorder that makes it harder to form social connections and then develop another one in adolescence, you’re playing a very different game. The reason I’m going to Horrible Therapist Youth Mental Health Clinic is because I can’t socialize anywhere else in this city and there are some pretty cool people there. I expect this to improve when living on campus/joining clubs/etc. I also know it might not. The horrible therapist is doing her best to help with this, I think, but her best is pretty awful.

          I also just want the opportunity to talk. My present therapist is extremely solutions-focused and pressures me for Problems! that she can Solve! using Excruciatingly Bad Acronyms!, whereas all my previous good therapists were goal-oriented too, but also very willing to just sit and talk and let me rant for ages about how terrible everything is. Therapy has the dodo bird verdict because the active ingredient is so often ‘sympathetic person lets you talk at them for an hour about your life’. This ties in with the social isolation (and is why therapy correlates with atomization in general).

  5. andrewducker says:

    Fascinating result recently on schizophrenia as a failure of synchronization: https://www.medicalnewstoday.com/articles/323094.php

    • vaticidalprophet says:

      While interesting, this is a mouse model of velo-cardio-facial syndrome first and foremost. VCFS has a far above average SZ risk compared to the general population, but it also has a neuropsychological profile in the absence of psychosis, and some traits of that mouse model could be more related to other VCFS symptoms, to the VCFS profile specifically (we don’t actually have much research on how similar VCFS psychosis is to SZ in the absence of the deletion), or to ‘generic disabling neurodivergence’.

  6. Jack V says:

    And if it is something like that, it’s easy to imagine that maybe it affects some people more than others — it gets worse for many people, but many people also reach an equilibrium.

  7. Tarhalindur says:

    I note with some interest that this predictive processing model of schizophrenia might have broader applications.

    There is, obviously, another situation in which sense data won’t match predictive processing: when you’re working off a busted model of the world, one that either couldn’t previously be falsified but now can or one that used to work but stopped doing so as conditions changed. The obvious thing to do then is to switch models, but sometimes people don’t – they don’t want to admit they’re wrong, or changing their model would cost them too much power and prestige, or (the classic) all of their social circles are using the same model and jettisoning it means losing the social circle, or the model has the memetic equivalent of a plasmid that encodes a poison and its antidote (like, say, “if you stop believing in this you go to Hell”). Or, even worse, the failing model could be a grand narrative, like Communism or the Roman conception of the gods and Imperial paterfamilias bringing benevolent order to the barbarian world, and the person has nothing to replace it with.

    I’m not versed with either the literature or anecdotal experience on the medium scale (though I’d wave in the direction of epicycles), but at the grand scale? Increasingly baroque explanations of how seemingly aberrant data actually fits the group’s existing model and/or doesn’t count, belief that the group is being targeted by an all-powerful but effervescent conspiracy bent on sabotaging them? Well, it sounds like an operative predictive processing model of evaporative cooling of group beliefs. Taken to extremes, it might also explain the psychology of witch hunts.

    (Maybe I should actually get around to reading that copy of When Prophecy Fails.)

    (Applications of this hypothesis to both sides of current American politics are left as an exercise for the reader.)

  8. Nancy Lebovitz says:

    What happens if you tell religious people who think God is speaking to them in vague symbols that in the Bible, God speaks in a clear voice?

    • baconbits9 says:

      I think that probably just eventually means “Does he have to use the bus” “yes” sounds like a really clear voice, cutting through the bustle on the street to be the only thing you hear.

      • Joe says:

        I think catholics have the advantage here. If you are a schizophrenic you have to remember that Our Lord taught us to love our enemies and bless those who persecute you. Also Catholics have a responsibility to obey thier spiritual directors or religious superiors. They shouldn’t just act on voices or intuitions on thier own.

        • Simon_Jester says:

          [nods]

          Maybe so.

          On the other hand, I’m pretty sure there are ample instances of medieval Catholics who believed the saints were speaking to them, and/or sending them messages in some way. Joan of Arc is of course a famous example.

          Now, I can see how living in a society where you’re systematically conditioned to obey the directions of some other person, as long as they are trustworthy and sane, will automatically tend to mitigate some of the bad effects of mental illness: “Don’t listen to your own revolving lava lamp of crazy, listen to Susie, she’s level-headed and will tell you what to do.”

          Of course, this leads to a massive smorgasbord of other entirely different problems, so meh.

        • JDG1980 says:

          Given how many Catholics there are, surely we must have some documented cases where the local bishop or other authority figure tried to talk sense into a Catholic schizophrenic who was “hearing voices from God”. Has anyone analyzed whether or not this had any positive effect?

    • uncle stinky says:

      In my psychotic episodes the voices are in no way vague or unclear. They aren’t God either but I couldn’t miss a word even if I wanted to. And Lord knows I have wanted to. Sometimes it can be represented through the modulation of existing sound and sometimes it’s just good old hearing voices but it’s absolutely unmistakeable.

  9. Quixote says:

    Posts like this are really good and really interesting.

  10. JRG says:

    Long time reader, first time poster. As it happens I am someone who works in this area (clinically high-risk individuals/early psychosis). I too was a big fan of the the Frith and Fletcher paper you mention, but more recently I have been reading Daniel Williams’ critiques of this as a theory of actual neural functioning per se. Here is a representative and strongly-argued sample:

    https://www.sciencedirect.com/science/article/pii/S1053810017306219

    He is a philosopher so this is not primarily empirical work, but his criticisms about Bayesian models being too flexible in some respects to be good theories of brain functioning (in the sense that good theories should perhaps be falsifiable) and the contention that the idea that human brains necessarily were selected for successively closer approximations of some kind of Bayesian reasoning without actually demonstrating that this is how cognitive systems beyond the very lowest level sensorimotor systems function are quite compelling. Similarly, the basic problem of what it means for there to be increasingly abstract levels of hierarchy without this becoming a kind of handwaving way of avoiding ever having to specify what the units of representation are strikes me as a really serious flaw in how these models work when discussing actual brains.

    As far as clinically high-risk folks go, we were all obviously tragically disappointed when the NEURAPRO trial failed to show any evidence that omega-3s were helpful in preventing transition. At the same time, part of why that trial failed is that they had a drastically lower-transition rate than the studies from the earlier days of the literature. Maybe specialist early psychosis services are actually helpful? I think the meat of intervention these days is felt to be in coordinated specialty care to arrest decline in functioning in chiefly non-pharmacological ways; additionally, CBTp is a very well-supported and real thing, although I am becoming increasingly interested in ACT for psychosis recovery because CBT is incredibly boring and is still wedded to the idea that logically defeating your own cognitions is the path to being more functional rather than cultivating a certain attitude or relationship to your own thoughts.

    I realise that last point may not be hugely popular here…

  11. Freddie deBoer says:

    a powerful idea of reference also overcame me from a television episode of Colombo

    I trace my intense paranoid fear of “the railroad police,” maybe the most consistent element of my hypomanic and manic states, to a minor scene in the film Into the Wild. As is typical with these things when I am manic I both know that any thoughts I have related to the railroad police are delusional and also that those thoughts are true in a way that surpasses understanding.

  12. Deiseach says:

    They focus on a statistic called Duration of Untreated Psychosis. The longer the DUP, the more chance psychosis has had to damage the patient before the fire gets put out and further damage is prevented.

    So what is it called when you can’t resist making stupid political jokes?

  13. chernavsky says:

    These people [critics of antipsychotics] tend to come up with kind of wild theories about how long-term antipsychotics hypersensitize you and make you worse. I don’t currently find these very credible

    I guess I find these theories more credible than you do. I’m glad you linked to the paper by Joanna Moncrieff, but a better source (though longer) is Robert Whitaker’s book, Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Of particular interest is Whitaker’s discussion of Martin Harrow’s study of outcomes in schizophrenia, and the result that long-term treatment with antipsychotic drugs is associated with worse outcomes.

    • JRG says:

      The major trouble is we have lots of descriptions of what psychotic disorders were like from the pre-neuroleptic era, and for many people they were severely disabling, progressive, and chronic. There is a disease process that is not 100% explicable by medication side effects.

      • chernavsky says:

        There is a disease process that is not 100% explicable by medication side effects.

        No reasonable person would claim that medication side-effects are the sole (or even primary) cause of schizophrenia. Certainly, neither Whitaker nor I believe that. The issue is determining the optimal treatment regimen for using antipsychotic drugs in schizophrenic patients. In his book, Whitaker argues that short-term use is probably beneficial.

  14. thedixon says:

    The very same mechanism would explain a lot about people who did a lot of psychedelics being weirder (there was a post some years back discussing that).

    Since “a fly flew by and it had cosmic significance” is a rather common occurrence on acid.

  15. JRG says:

    I can’t reply to the young man above who was worried he might be developing psychosis, but if you do have this fear, here is a link to a directory of early psychosis intervention programs organized by state if you are in the US:

    http://www.easacommunity.org/files/Early_Psychosis_Intervention_Program_Directory.pdf

    This list is not at all complete so do not necessarily despair if none of these are near you. If anyone worried wants to put up a general geographic region I would be happy to identify the closest center that is not actually a bunch of hacks.

  16. arlie says:

    I wonder how many people experience what you call the schizophrenia prodrome, and never develop full blown schizophrenia, without ever taking anti-psychotic drugs.

    The specific population I’m curious about are those who develop explanations which mostly allow them to participate normally in ordinary reality. If, of course, they exist.

    Consider for example religious visions, in combination with a cultural explanation that basically says – these occur, and should not be taken literally, in fact if you have them you should consult (and be supervised by) a spiritual advisor of some kind, whose training and experience will generally bias them in favour of teaching you to see the visions as inscrutable and yourself as not especially special. I.e. they happen, and you shouldn’t expect them to appear consistent with ordinary reality, or even especially meaningful to your limited human intellect – like dreams only less so.

    If (some) religious visions are basically schizophrenic symptoms – and that’s where I have no reliable knowledge – various traditional ways of handling them might tend to be protective.

    Or on the other hand, I’m acquainted with a person who basically says “yes, I have things that seem like religious visions; I chose to believe they are a manifestation of faulty brain wiring, not real at all – and by the way, religion is a human construct; there is no real God.” She’s a bit odd, but not in psychotic-seeming forms. And she retired after a successful career in tech – which is where I knew her, and her explanation for her experiences.

    So basic question – and obvious null hypothesis – is this like (some) early cancer screening, which appears to find (and treat) an awful lot of things which would (statistically) have mostly cleared up on their own, rather than developing into full blown cancer.

  17. IsmiratSeven says:

    New King’s Road obviously was “the road of the New King” (Jesus), and my suicide would thrust “the old king” (Satan) out of me and Jesus would return to the world to rule. I then would be cast into Outer Darkness fighting Satan all the way. The monumental, world-saving grandiosity of this lamentable act was a far cry from my totally irrelevant, penniless, and peripheral existence in Hackney a few months before. In my own bizarre way, I obviously had moved up in the world. Now, I was not an outcast from it. I was saving the world in a very lofty manner. Medical authorities at Charing Cross Hospital in London where I was taken by ambulance, initially, of course, to orthopedics, fairly quickly recognized my psychotic state. Antipsychotic drugs were injected by a nurse on doctors’ advice, and eventually, I made a full physical and mental recovery.

    Sounds like the delusions were pretty damn accurate.

    If I had Scott’s gift for quick fiction, I’d write the parallel universe version of these events, where he throws himself in front of a bus on an unsigned depot-accessway instead of New King’s Road and dies before paramedics can intervene.

  18. jhertzlinger says:

    In other words, schizophrenia frequently starts by someone thinking “This is not a coincidence because nothing is ever a coincidence.”

  19. evolutiontheorist says:

    The most sensible reason to treat schizophrenia early is that it is a harmful, often terrifying condition for both the sufferer and people around them. Further, it is probably a lot easier to get people on treatment while they are still partially sane, have an address, aren’t convinced that you’re trying to poison them, and haven’t disappeared under a bridge somewhere. Schizophrenia medications certainly have side effects, but the side effects of not treating schizophrenia are pretty big.

  20. John Schilling says:

    Assuming this is true, how do we do anything useful with it in a society that has severely stigmatized mental illness for generations and doesn’t have much in the way of privacy any more? I don’t think there’s any realistic way to say “you should start taking antipsychotic drugs, at least for now”, without being heard as “you are psychotic, and we’re going to make that an official pronouncement”.

    • Simon_Jester says:

      Well, the starting point might be “anti-psychotic drugs don’t just block psychosis, they can also sometimes prevent psychosis from forming.” We already put surgery patients on antibiotics as a precaution sometimes; this isn’t fundamentally that different in principle.

    • Scott Alexander says:

      Good news! Drug companies have pushed antipsychotics so hard that people take them for depression, anxiety, and even insomnia! We can just be like “Yeah, take this medication, it’s the same one your grandma takes when she can’t sleep”

  21. greghb says:

    The incidental link to the paper, “Statistically Controlling for Confounding Constructs Is Harder than You Think” is terrific! I’ve had a vague instinct that this must be the case. It’s very cool to see it explored thoroughly.

    This pitfall seems like it adds additional problems with believing social science studies, over and above the usual replication crisis stumbling blocks of researcher degrees of freedom / p-hacking / forking paths.

    • untimelyreflections says:

      > Statistically Controlling for Confounding Constructs Is Harder than You Think

      Much more much is out there on the fallacies of ‘controlling’ in the literature on causation and probability.

      See e.g. Judea Pearl “Causation” also his other book on the topic, more popular “The Book of Why”.

      See also the list of assumptions for multiple regression (for the individual terms to be valid) https://en.wikipedia.org/wiki/Regression_analysis#Underlying_assumptions, which are almost never actually met in any real study.

  22. quitelikelyblog says:

    It’s fascinating how many altered mental states come down to how much credence the brain gives to patterns it thinks it sees. My experience with psychedelic drugs has been that they make it a lot easier to crystallize patterns – meaning you see real patterns you otherwise wouldn’t, but also see more bogus patterns than you otherwise would. This makes it sound like schizophrenia is basically occasional sudden jolts of the same effect.

  23. Callum G says:

    Could this mean that providing a regular, understandable environment to people with negative symptoms of schizophrenia could help? Such as a basic video game?

    • Simon_Jester says:

      Hm.

      “Effects of Bejeweled on Schizophrenia.”

      Sounds like a viable research paper.

    • Scott Alexander says:

      I don’t think so. You’d just have some kind of weird epiphany about the Tetris L-block and start believing it stands for Lucifer or something.

    • vaticidalprophet says:

      Depends. You’ll probably have to code an individual video game for basically everyone’s eccentricities, e.g. the heavy-negative-symptoms person I know won’t watch non-anime media because she’s afraid of 3D people. Could be interesting, though.

  24. Well... says:

    Suppose one could prove that with some kind of advanced AI we’d be able to model both the human mind and brain extremely realistically down to a neurological level, and therefore be able to conduct millions of trials without any ethical risk to actual humans, and therefore be able to cure mental illnesses. How much would that change the AI risk conversation, and in what way?

    • Lancelot says:

      I’d say that conducting experiments on fully simulated humans is pretty much morally equivalent to experimenting on actual humans, hence it doesn’t actually solve anything.

  25. DoglessHeathen says:

    Are there are any credible studies showing the effects of religious upbringing on the likelihood of schizophrenia ?

    One can speculate that having people incepted with a well developed universal-sentient-conspiracy model at their formative stages will make them more susceptible or conversely might immunize them from having their normal prediciton mechanisms taken over.

  26. RC-cola-and-a-moon-pie says:

    One thing I don’t understand about the model of schizophrenia presented in the post is this. If the basic mechanism is a rational or somewhat rational adaptation of beliefs to incorporate abnormal perceptions, one might expect a schizophrenic to articulate a more or less rational explanation of his belief system or worldview, allowing for difficulties explaining why, say, the television advertisement seems so obviously to be speaking to him. I’ve never spoken with a schizophrenic but my layman’s perception is that such a conversation with a schizophrenic would actually go down quite differently, with highly abnormal inferences, strange linguistic idiosyncrasies, and a general inability to sustain prolonged chains of inferential thought. That would lead me to think a priori that there ought to be something deeper going on than updating views to accommodate erroneously perceived input data. But hey, what do I know.

    • Simon_Jester says:

      Remember that in the model Scott is using here, the first symptom is fundamentally irrational convictions. At this stage, you could reasonably expect an articulate explanation of why these irrational convictions lead to the dysfunctional worldview.

      But then we get to the subsequent stages. Where the schizophrenia has been going on long enough and producing a constant enough rain of seemingly random but highly significant stimuli that NO model of the world makes much sense anymore.

      At which point the structured mental processes they’ve been evolving since childhood, the ones that are used because they work, are no longer registering as “working.” Nothing makes sense anymore, acting randomly or repeating catchphrases produces results that seem as significant/valuable as all the old ways, the risk-reward mechanisms are well and truly fucked.

      And that’s when you start to see highly ‘weird’ behavior (because they tried it once on impulse and an angel told them ‘good job’ in a pattern of sunlight on a cloud or something).

      And inability to carry on a coherent conversation (because their mental model of YOU isn’t coherent anymore, so they can’t figure out what to say to you, so they start throwing words at the wall in hopes that it’ll stick).

      And inability to carry on extended chains of inferential thought (the universe is plainly dominated by the conspiracy to gaslight me by constantly barraging me with significant but seemingly random stimuli, nothing really makes sense anymore, logic is overrated, let’s explore free-association instead!)

      Under the model in question, all these things are reactions to the structured, ordered thought processes themselves being eroded by prolonged exposure to a process that interprets random stimuli as evidence that one needs to alter one’s worldview in random directions. And in this model, the meta-process of “what processes do I use for thinking, and how do I think about the people and things around me” proceeds on a largely subconscious level. Even if outsiders can analyze it in terms of sensible models about evidence and priors and heuristics… Well, while it’s going on, we usually don’t have a lot of access to the process.

    • vaticidalprophet says:

      > If the basic mechanism is a rational or somewhat rational adaptation of beliefs to incorporate abnormal perceptions, one might expect a schizophrenic to articulate a more or less rational explanation of his belief system or worldview, allowing for difficulties explaining why, say, the television advertisement seems so obviously to be speaking to him. I’ve never spoken with a schizophrenic but my layman’s perception is that such a conversation with a schizophrenic would actually go down quite differently, with highly abnormal inferences, strange linguistic idiosyncrasies, and a general inability to sustain prolonged chains of inferential thought.

      Depends on baseline cognitive functioning, current relationship with consensus reality, and how conservatively you the viewer define ‘abnormality’. I think I could articulate a rational-adjacent argument for why it’s a reasonable conclusion the universe is controlled by entities dedicated to suppressing nonconformity. I probably couldn’t convince an empirical atheist it’s controlled by dark alien angels living in the spaces between realities, but if we ignored that bit I’d sound sane enough. I am, of course, less inclined to do this when I can argue it more coherently and vice versa.

  27. DoglessHeathen says:

    I was wondering if I should go to the store, and then a Nike ad came on that said JUST DO IT. I knew that was somehow significant to my situation, so I figured Nike must be reading my mind and sending me messages to the TV.” Then you’ll remind them that that can’t happen, and even though it seemed so interesting that Nike sent the ad at that exact moment, they’ll back down.

    Or they will remind you that this is the 2018 bay area and they were just talking about Nike the other day at dinner in the context of the kneeling players controversy and mentioned they need to get groceries on a phone call to a friend and they have an average of 2.7 internet-connected-always-on-speech-analyzing-brand-keyword-detecting devices in their vicinity at any given time and their TV is a super smart one and really the only surprising thing is that it didn’t say “JUST DO IT, Patient J. Person !” and suddenly those precious prediction priors don’t seem as useful anymore.

    • Nancy Lebovitz says:

      I hallucinated that you wrote ““JUST DO IT, Patient J. Peterson !”, and I was trying to figure out the exact snark and then the snark turned into a boojum.

  28. thepenforests says:

    So, probably a stupid question that I have to ask anyway: assuming this entire model of schizophrenia is true, is there any chance that merely knowing about the model itself could be self-inoculating? Like, say we blasted this message out to every corner of society: schizophrenia is a disease of salience; it progresses via a poorly understood positive feedback loop where the brain attaches unwarranted significance to minor events, and then uses the fact that previous minor events had significance to feel more justified in attaching further significance to further minor events, which in turns leads to a self-reinforcing worldview that eventually becomes completely detached from reality.

    Say we did that. Could it be that maybe some sufficiently self-reflective subset of the vulnerable-to-schitzophrenia population could use this message as a kind of mantra to help avoid slipping further and further into the disease?

    Like, if this were part of common cultural wisdom, maybe when someone noticed a bug land on them, instead of saying “Aha! Bugs must be very important to me in some fundamental, ineffable way! Maybe….maybe someone is bugging me! And bugs even have antennas, so clearly they’re using antennas to bug me. It all fits!”, they’d instead say “Oh yeah, this is one of those classic things where my brain is trying to impart meaning to situations that don’t deserve it, just like I heard about in Psych 101, I should just ignore it”. And then the feedback wouldn’t develop.

    And I mean, probably this is total nonsense. I have a vague sense that there’s been no shortage of people throughout history who have tried to use logic and reason or whatever to get people to “think themselves” out of mental illnesses, and it’s never worked, because mental illness is complicated.

    But on the other hand, the model proposed in this post is a pretty radical one; it seems to be saying that in some fundamental sense, schizophrenia is a disease that pertains to how the brain is structured. Chemical imbalances may be involved at the start, like say in producing the dopamine surges or whatever that lead to the initial unwarranted salience. But once you’ve progressed further than that, what really characterizes the disease (again, at least according to [my understanding of] this model) is that your neurons just aren’t wired up the right way anymore; the high-level structure of your brain has been modified in such a way that it no longer can make accurate predictions about the world.

    If that’s actually true though, then it doesn’t seem totally crazy to me that certain ways of thinking really could be preventative against schizophrenia. We can definitely access (and change) the structure of or brain through thought; thinking absolutely rewires our neurons, and so maybe high-enough level thinking could be preventative against certain kinds of neuronal feedback loops, and maybe that could be preventative against schizophrenia in general.

    I am more than willing to believe that I’m just talking nonsense though, please people who actually suffer from this kind of thing don’t get offended. I obviously don’t understand it, and I’d love to hear exactly why I’m wrong. Like, I’m definitely not trying to say that if someone was “smart enough” they wouldn’t have fallen victim to schizophrenia, I know that’s wrong. But I still wonder if the role of reflective thought in the progression of the disease might not be relevant if this model is true.

    • Null42 says:

      I don’t think it’s nonsense at all. I mean, there are certainly people for whom it won’t work, and they’re probably even the majority…but that doesn’t mean learning about the way it works won’t help *anyone*. It’s like the bit about doctors telling their patients to quit smoking…it works in about 2% of patients, which turns out to save a lot of lives over the course of a primary care provider’s career. So I think a neuroscience-inflected version of therapy tailored to the schizophrenic prodrome has at least the possibility to do some good, and should definitely be tried, if it hasn’t already.

    • JDG1980 says:

      Like, say we blasted this message out to every corner of society: schizophrenia is a disease of salience; it progresses via a poorly understood positive feedback loop where the brain attaches unwarranted significance to minor events, and then uses the fact that previous minor events had significance to feel more justified in attaching further significance to further minor events, which in turns leads to a self-reinforcing worldview that eventually becomes completely detached from reality.

      For starters, you’d have to formulate that message in a manner that someone with an average IQ could understand.

    • Doktor Relling says:

      Thepenforests writes: “assuming this entire model of schizophrenia is true [i.e. schizophrenia starts with aberrant prediction errors; the brain becomes incorrectly surprised by some sense-data], is there any chance that merely knowing about the model itself could be self-inoculating?”

      In lighter cases (such as brief reactive psychosis), my admittedly limited experience suggests that Thepenforests can be right. Simply making the patient aware that there exists a fairly well-established theory of how what he/she experiences can be explained, can be of help to the patient: i.e. “relax, this is just standard good old madness, and now I will tell you the theory of how this type of madness comes about.”

      A story of how this type of madness comes about can be of help because it provides a narrative that gives the experiences a different meaning than a metaphysical meaning. Suggesting an authoritative alternative narrative is helpful, since the metaphysical narrative (the patient believes that he/she may have a mystical experience) can lead in very dangerous directions, as Peter Chadwick’s story illustrates.

      The “secular” narrative the theory provides (well, actually, any type of “secular” theory of the experiences), can represent the push the patient needs to strive to disregard the “messages” he/she receives, and the “messages” will then hopefully become weaker over time. You mobilize the will of the patient to look the other way. (Alternatively framed: It becomes rational to try to look away.) Otherwise, the feeling of ”wow, I may have contact with a mystical realm, just like the old sages” can tempt the patient to maintain, or at least not actively try to disregard, the “messages”. As Peter Chadwick’ story also illustrates, this is in a sense a very interesting and flattering story to tell oneself. Which sane person would like to look away from a genuine mystical experience, right?:-)

      But I am far less certain that this strategy is of much help to patients who are schizophrenic, in particular if the schizophrenia has “settled”. Which was Scott’s starting point. So it’s important with early intervention here too.

      In short: This “intellectual” strategy may work for patients who are as yet unsure as to the meaning of what they experience – the types who come to their doctor saying “I have these weird experiences when watching a TV program, which frightens me and I try to make sense of” – rather than those who come to their doctor and say “the people in a TV program I watch, send me messages that hurt and humiliate me.”

  29. Null42 says:

    A bit offtopic, since the vast, vast majority of schizophrenics are not in such positions, but for some reason I am reminded of James Jesus Angleton, head of counterintelligence in the early Cold War CIA, who was obsessed with moles in the CIA and ruined a lot of people’s lives…and when he retired, the CIA actually did fill up with a number of KGB moles! The whole type I-type II error thing is hard to tease out in some fields.

    I wonder how actually having large international organizations conspiring against you ties into all this. Or, more practically for Scott, how the patient’s religious background and the general level of actual persecution in their past affects treatment.

  30. nameless1 says:

    Scott,

    What happens when you do the opposite: you experience weird things, so you decide to shut out the world for preserving your inner sanity (logic, model) ? This may explain depression. Actually pretty well. Losing an interest in the world around, retreating in an internal world etc. of course it could also be being schizoid or a number of other things. I just want to say the opposite happens, too.

    Is it common for long term depressed people to have been the kids with overly active imaginations, bordering on the psychotic?

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