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OT79: Open Road

This is the bi-weekly visible open thread. Post about anything you want, ask random questions, whatever. You can also talk at the SSC subreddit, the SSC Discord server, or the Cafe Chesscourt forum. Also:

1. A study on mathematical ability is looking for people without a diagnosis of autism with a degree in math, or people with a diagnosis of autism with a degree in math, physics, statistics, etc to register and do some brief online tests for them. They asked me to pass the word along. If you’re interested, go to the Genetics Of Mathematical Ability And Autism research site.

2. I’ve been getting a lot of emails from people here recently, which I guess is good, but I want to admit straight out that I’m not able to reply to all of them. This is especially true for “Hey, what do you think about this thing I wrote?” emails. Usually I think that I don’t have time to read it and write up a response, but I feel guilty not doing that, so instead I just say something like “Thanks, I’ll look into that” and then I don’t. Sorry if this is you. Also, please don’t send me links for the link page. If you have a good link for the links page, post it on the subreddit and I’ll probably see it. I’ll continue to accept useful announcements about studies and job opportunities and EA and so on, like the thing above.

3. Thanks to everyone who came to the Chicago meetup today. Picture here. And if you want to stay in touch with the community, there’s a Chicago Rationality Facebook page with information about meetings and stuff.

4. Ward Street is quickly becoming the center of the rationalist scene in Berkeley. We’re trying to encourage that so that as many people as possible can live near each other and it can feel like more of a community. I’ll be staying there temporarily when I first get to California, and I know a lot of other people on the street and they’re all pretty interesting. Anyway, there’s a house opening up there as the current residents leave, and we’d like to get rationalist-adjacent people to move in. It’s three bedrooms, one bathroom, and it costs $4100/month total. If interested (either in renting the whole house with friends/family, or in just renting one room and hoping two other people want the same), email jsalvatier[at]gmail[dot]com and he can tell you more / help connect interested parties together.

5. Probably some decreased blogging output since I’m moving cross-country the next few weeks. I hope to have a couple of meetups in relevant cities if I know where I’m going to be enough days beforehand.

6. Good luck/congratulations to everyone starting/progressing in/finishing residencies this July.

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To The Great City!

Related: 0/4, 1/4, 2/4, 3/4

Last Friday I said goodbye to my patients, handed over my pager, and left Our Lady Of An Undisclosed Location for the last time.

I was hoping for a moment for quiet reflection, but I made it about halfway to the door before being accosted by an incoming intern who couldn’t figure out how to use the medical record system. I helped her, because I’d definitely been there before. I was looking back over my blog archives from four years ago, when I started all of this, and I’d written:

If you’re entering medical residency and want to prepare, practice this phrase: “I don’t know the answer to that question, but I’ll page my senior resident and he will get back to you.” I keep getting paged by nurses with questions like “Your patient in room 315 has critically low potassium, please advise.” And I went through medical school and I know stuff about low potassium and I have clever ideas for what to do and probably in over 80% of cases those ideas would not kill the patient. But “over 80%” isn’t enough, so each time I have to find my senior, who’s really busy and hates getting paged just like everyone else, and ask him a stupid question I already know the answer to.

And even though it seemed kind of unlikely at the time, that thing which happens to the people in all of those medical shows like Scrubs happened to me. I survived intern year. I developed some vague foggy idea what I was doing. At some point I crossed the border into competence. I started becoming one of the people who answers the clueless questions instead of one of the people who asks them.

I can’t say enough nice things about my hospital. They put up with me through all those years I didn’t really know what I was doing, invested thousands of hours into training me. They answered all my rookie questions, like “why can’t patients wear shoes with laces?” (answer: because you can tie shoelaces into a noose to hang yourself with) or “why do we have to learn this style of therapy when studies show it’s no more effective than empathetic listening?” (answer: because the government says so). Everyone knows the stereotypes about residency – you’re overworked, you’re abused, you’re treated like pond scum – and my hospital put the lie to every single one.

And I can’t say enough nice things about the other residents in my program. I’ve never been good at making friends, but being thrown into the lion pit together is a pretty powerful form of bonding, and after the existential terror of intern year where some twenty-something-year-olds who have been to medical school but are otherwise pretty normal people get shoved into a hopital and expected to treat patients together, I think we became pretty close. I never had to trust them with my life, but I trusted my patients’ lives to them every day. I’ve strategized first dates with them, been to their weddings, cooed over their newborn babies. Um. Had several-year-long arguments about consciousness with them. Met the gurus of their obscure religions. Good times.

But Kurt Vonnegut writes about the difference between two kinds of teams. A granfalloon is a team of people pushed together for some ordinary human purpose, like learning medicine or running a hospital psychiatry department. They may get to know each other well. They may like each other. But in the end, the purpose will be achieved, and they’ll go their separate ways.

A karass is a group of people brought together by God for some purpose of His own. No matter how little time they spend together, or how poorly organized they might be, they’ll always be on the same wavelength and have a special kinship with each other.

And all the wonderful and compassionate people I got to know during my four years in Michigan are my granfalloon. I’ve never stopped feeling like you guys – the rationalists, the effective altruists, the transhumanists, the AI scientists, the statisticians, and all the rest – are my karass. All these years I’ve had to spend away from you have felt a little bit like exile.

Back when I first left the Bay Area to take this position four years ago, I wrote myself a letter. I said that I know about value drift as well as anybody. People always say that they’re going to love their first girlfriend forever, and then it never happens. Or they say they’re going to keep in touch with their college friends, and then they forget. But – 2013-me wrote to 2017-me – if your values drift so far that you find yourself wanting to stay in Michigan, just…take a step back and think about it. Remember all the friends you have out west, and how exciting the intellectual climate is, and your feeling that it’s some kind of fulcrum for the forces that will produce the future, the sort of place that Athens must have felt like in 400 BC, or Florence in 1400. And before you end up marrying some Michigan girl and opening up a practice across the street from the hospital where you trained, just remember everything out here and how much you used to love it.

And even though I had a better time in Michigan than I could possibly have hoped – even though Detroit pizza is literally my favorite food ever and I’m kind of panicking at the idea of being somewhere you can’t get it delivered – despite all of that I didn’t even have to open the letter. I remember everything in it perfectly clearly. My values haven’t drifted at all. All of you are great.

So I’m happy to be able to announce that I’ve just accepted a psychiatrist position in the San Francisco metropolitan area – the greatest metropolitan area in the world! I’ve cancelled my lease, loaded everything I own into the trusty little Subaru I got before I realized that driving a Subaru in Detroit would earn you constant dirty looks, and am very gradually moving west.

Thanks to all of you for keeping in touch and helping me stay sane these past four years. I’ll be seeing you very soon.

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SSC Meetup: Chicago 7/2

I’ll be in Chicago this weekend along with Katja Grace of AI Impacts.

If you want to hang out, let’s meet at the Starbucks on 200 S Michigan Ave (right near the Art Institute) at 5:00 PM Sunday 7/2.

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Why Are Transgender People Immune To Optical Illusions?

[Epistemic status: So, so speculative. Don’t take any of this seriously until it’s replicated and endorsed by other people.]

I.

If you’ve ever wanted to see a glitch in the Matrix, watch this spinning mask:

Source: http://hearingthevoice.org/2013/11/14/predictive-coding-masterclass/

Did you see it? As the face started to turn away from you, your brain did…something, and then you were seeing a normal frontwards-facing mask again. It turns out your visual system has really strong views about whether faces should be inside-out or not, and it’s willing to execute a hard override on perception if it doesn’t like what it sees.

But not always. Some people get glitchier glitches than others; a few seem almost immune. Studies find schizophrenics and autistic people to be consistently less glitchy than the rest of us. The correlation’s not perfect. But it’s definitely there. Something about these people’s different cognitive processing styles lets them see through the illusion.

I wanted to replicate this result myself. So a few months ago, when I surveyed readers of my blog, I included some questions about perceptual illusions (including a static version of the hollow mask). I got five thousand responses, including a few from schizophrenic and autistic readers. Sure enough, the effect was there.

Schizophrenic readers were about twice as likely to report a weak reaction to the mask illusion as non-schizophrenics (28% vs. 14%, p = 0.04). They were also more likely to have a weak reaction to a similar illusion, the Spinning Dancer (58% vs. 81%, p = 0.01). Readers with a family history of schizophrenia landed in between schizophrenics and healthy controls (16% for mask, 63% for dancer, ns).

Autistic readers were only slightly more likely to report a weak reaction to the mask illusion than neurotypicals (17% vs. 14%), but thanks to our big sample size we could be pretty confident that this was a meaningful difference (p = 0.004). There was no different between autists and neurotypicals on the Spinning Dancer, not even a weak trend (58% vs. 60%, p = 0.4).

Looking deeper, I found a few other anomalies on illusion perception. Most were small and inconsistent. But one stood out: transgender people had an altered response pattern on both illusions, stronger than the alteration for autism and almost as strong as the one for schizophrenia (mask: cis 14% vs. trans 21%, p = 0.003; dancer: cis 58% vs. trans 71%, p = 0.001). These results are very tentative, and need replication. My mass survey isn’t a very sensitive instrument, and I place low confidence in any of this until other people can confirm.

But for now, it sure looks like a signal. Something seems off about transgender people’s perception, something deep enough to alter the lowest-level components of visual processing. If it’s real, what could it be?

II.

A few days ago, trans blogger Zinnia Jones asked me if there might be any neurochemical reason trans people dissociate so much.

Dissociation is a vague psychiatric symptom where you feel like you’re not real, or the world isn’t real, or you’re detached from the world, or something like that. It sounds weird, but if you explain it to someone who’s had it, they’ll say “Oh yeah, that thing!” It’s usually unpleasant, and tends to occur in PTSD, borderline personality, and extreme stress.

And in transgender people. The only formal study I can find on this describes it as “greatly prevalent”, and suggests that up to 30% of trans people may have dissociative conditions (compared to less than 1% of the general population). This matches trans people’s self-reports (1, 2, 3, 4, 5). Anecdotally (according to Zinnia’s impression of the trans community) and formally (see Costa & Colizzi 2016) hormone replacement therapy is an effective treatment for dissociative problems.

Intuitively this makes sense. Trans people feel like they’re “trapped in the wrong body”, so of course they feel detached from their bodies / like their bodies aren’t real / like their bodies aren’t theirs. Hormone therapy helps solve the “wrong body” problem, so it also solves the dissociative symptoms.

We aim to bridge psychosocial and biological levels of explanation. We can say that someone is stressed out because their boss overworks them, but also because they’re secreting high levels of cortisol. We can say that someone is depressed because they broke up with their boyfriend, but also because they have decreased synaptogenesis in their hippocampus. Causation gets tricky, and this is a philosophical minefield for sure, but overall these two levels should be complementary rather than competitive. So what’s the biological correlate to trans people having dissociation problems?

Practically all searches for the biological basis of dissociation end up at the NMDA glutamate receptor, one of the many neurotransmitter systems in the brain. Even though its cousins dopamine and serotonin usually get top billing, glutamate is probably the brain’s most important neurotransmitter, and NMDA glutamate receptors in particular are involved in all sorts of interesting things.

Drugs that block NMDA receptors cause dissociation. The most famous dissociative anaesthetic, ketamine, is an NMDA antagonist. So is DXM, a recreational drug that causes dissociation in abusers. Wikipedia’s list of dissociative drugs is basically just fifty-five NMDA antagonists in a row. The only other category they list are kappa opioid agonists, and kappa opioid agonism probably – you guessed it – antagonize NMDA. If we take this result seriously, every substance we know of that causes dissociation is an NMDA antagonist in some way.

Does anything improve NMDA function – an effect we might expect to alleviate dissociation? Yes, and among a list of intimidating research chemicals called things like “aminocyclopropanecarboxylic acid” is one familiar name: estrogen. See eg El-Bakri et al, which finds that “estrogen modulates NMDA receptors function in the brain…enhancing NMDA function”. McEwen et al: “One of the long-term effects of estradiol [estrogen] is to induce NMDA receptor binding sites in the CA1 region of the hippocampus.” Bi et al: “17-B-estradiol [estrogen] enhances NMDA receptor phosphorylation and function.” I don’t fully understand this research, but it seems to point to estrogen promoting NMDA activity in some way.

So transgender people dissociate a lot, a state usually associated with hypofunctioning NMDA receptors. And trans women get better when they take estrogen, a hormone that improves NMDA function. That’s interesting. But what does this have to do with those optical illusions?

III.

The Hollow Mask illusion and its cousins may depend on NMDA function.

To oversimplify: the brain interprets the world through Bayesian calculations. In Corlett et al’s model, it communicates top-down priors (ie assumptions based on previous knowledge about the world) through NMDA receptors and bottom-up new evidence through AMPA receptors. They write:

In a hierarchical cortical system in which representations become more abstract with increasing distance from the primary input, higher levels of the hierarchy specify top-down predictions through NMDA receptor signaling and any mismatches between expectancy and experience are conveyed upward through the hierarchy via rapid AMPA and GABA signaling

When you see a hollow mask, the brute facts of how the mask looks are your bottom-up sensory evidence. Your top-down prior is that every other face you’ve seen for your entire life has been normal, not inside-out. Given the strength of the prior, the prior wins, and your brain interprets the mask as a normal face.

Unless your brain is bad at applying priors, ie its NMDA receptors aren’t working that well. Then it just sticks with the bottom-up sensory evidence showing that the mask is hollow.

Schizophrenia and autism both probably involve decreased NMDA function in different ways. For schizophrenia, see eg Olney, NMDA receptor hypofunction model of schizophrenia, and Coyle, NMDA receptor and schizophrenia: a brief history. Ketamine seems to replicate the symptoms of schizophrenia pretty well and is commonly used as a model for the disorder. For autism, see eg Lee, NMDA receptor dysfunction in autism spectrum disorders and this study where screwing with NMDA receptors in mice seems to turn them autistic.

From this we would predict that estrogen would help treat schizophrenia and autism. It does. Schizophrenia is more common and more severe in men than women, with researchers noting that “gonadal steroids may play a role in buffering females against the development of schizophrenia”. Women are known to sometimes get schizophrenia triggered by menopause when their estrogen levels decrease. Estrogen supplementation is an effective schizophrenia treatment, and there’s some interest in developing estrogen receptor modulators that can help schizophrenic men without making them grow breasts. Meanwhile, autism continues to be about four times more common in men than women, autistic women tend to have more “male-typical brains”, and although it’s considered unethical to treat autistic boys with estrogen, it works in mice and fish. Once again, doctors are looking into estrogen analogues that don’t turn people female as possible autism treatments.

We might also predict that estrogen would increase glitching on the hollow mask. I can’t study this directly, but on the survey, 15% of biological males had weak reactions to the illusion, compared with only 11% of biological females, p = 0.01. Since women have more estrogen, that looks good for the theory.

Transgender people have higher rates of autism and schizophrenia. The Atlantic actually had a good article about this recently : The Link Between Autism And Trans Identity. They cite one study showing 8% autism rate in trans people (compared to 1-2% in the general population), and another showing that autistic people were 7.5x more likely to express “gender variance”. Apparently a lot of trans people have problems getting hormone therapy because their doctors think the gender issues are “just” because of their autism. Some might say that denying people estrogen because they have a condition which studies suggest estrogen can successfully treat is a bit, I don’t know, crazy and evil, but I guess people get really weird around this stuff.

My survey broadly confirms these numbers. Autism rates were sky-high in every category – it’s almost as if the sorts of people who like reading blogs about how gender is all just NMDA receptors skew more autistic than average – but there was a remarkable difference across gender identities. 15% of cisgender people were autistic, but a full 52% of trans people were.

The survey also finds that about 4% of non-schizophrenic people were transgender, compared to 21% of schizophrenics and self-suspected schizophrenics. Other people have noticed the same connection, and I’ve met more schizophrenic transgender people than I would expect by chance given the very low rates of both conditions.

If this is right, we end up with this rich set of connections between schizophrenics, autistics, ketamine, dissociative experiences, estrogen, gender identity, and the hollow mask. Anything that decreases NMDA function – schizophrenia, autism, ketamine – will potentially cause dissociative experiences and decreased glitching on the mask illusion. Estrogen will improve NMDA function, treat dissociative experiences, and bring back hollow-mask glitching.

So I wonder: is NMDA hypofunction related to transgender? That would explain the autism and schizophrenia connections. It would explain the hollow mask numbers. It would explain the dissociation. It would explain why estrogen helps the dissociation. And it would explain a lot of internal connections between all of these different conditions and factors.

IV.

I’m going to stop here, even though there’s a lot more worth saying on this, because I’ve already gotten so far into Speculation Land that trying to chain any more conclusions on would probably be premature. So let’s switch to some reasons for skepticism.

First, the research into NMDA receptors is too interesting. People argue that NMDA is key to depression, key to anxiety, OCD, chronic pain, and borderline personality (my guess is the depression claims are mostly overblown, the borderline claims are 100% absolutely right and revelatory, and I’m agnostic on the others). On the one hand, explaining everything sounds sort of good. On the other hand, it also sounds like what would happen if a field was getting kind of overhyped and slipping into methodology loose enough to prove anything it wanted. Maybe a vague link between a receptor which is literally everywhere in the brain and some psychiatric disease isn’t that interesting. A theory that can explain absolutely everything should always cause suspicion.

Second, I’m still not sure what to make of the Hollow Mask results on my survey. Although the transgender results were unusually strong, I did get mildly statistically significant results on about half of the thirty-or-so things I looked at, including seemingly-unrelated items like political affiliation. Some might argue that this means something is wrong with my survey. Others might argue that hey, we know political attitudes are about 50% genetic, and the last time people tried trace the genes involved all the strongest results were genes for NMDA receptors. Have I mentioned that NMDA receptors are really interesting?

Third, I included a second illusion I asked about on the survey, the Spinning Dancer. It also had an odd response pattern among transgender people. But it didn’t correlate at all with the Hollow Mask Illusion, and it doesn’t seem to be elevated among autists. I don’t know what’s going on here, and the whole thing makes me more suspicious that all of this is some weird artifact.

Fourth, all this predicts that ketamine will cause reduced glitching on the Hollow Mask. It doesn’t. Corlett argues that this is because chronic, but not acute, NMDA dysfunction is required to stop the hollow mask glitches “because [keatmine] has a predominant impact on bottom-up AMPA signaling”. I don’t really understand this and it seems like a prediction failure to me. On the other hand, chronic marijuana use does prevent mask glitching, which might be because of marijuana causing NMDA hypofunction over time, which I guess is a point in favor of the chronicity theory.

Fifth, although trans women dissociate less when they take estrogen, trans men dissociate less when they take testosterone. I can’t find whether testosterone has similar NMDA-promoting properties in the brain, although it sometimes gets aromatized to estrogen so that might be relevant. Also, I’ve never heard of any trans woman taking testosterone or trans man taking estrogen. If that makes dissociation worse – and from the psychosocial perspective it probably should – then that would be a strike against this theory.

Sixth, although I played up the transgender/autism and transgender/schizophrenia links, the truth is that transgender people have higher rates of every mental illness, to the point where it may just be some general factor. I think I’m justified in focusing on these two results because transgender people’s higher rates of depression and anxiety are probably just related to being transgender being depressing and anxiety-provoking in this society. But schizophrenia and autism are 80+% genetic, and so harder to explain away like that. Still, somebody could question the relevance of worrying about these two conditions in particular.

I hope some of this can be sorted out in the near future. A first step would be for someone official to replicate the transgender Hollow Mask pattern and prove that it’s not just confounded by autism and schizophrenia rates in that population. A very tentative second step would be to investigate whether chronic use of the supplements that improve NMDA function in schizophrenia – like glycine, d-serine, and especially sarcosine – can augment estrogen in improving gender dysphoria. Remember to consult your doctor before trying any weird supplements since they may cause unintended side effects, like becoming a Republican.

It could also be worth trying to understand more explicitly why gender identity and NMDA should be linked. This post is long enough already, but I might write more on this in the future. If you want a preview, check out The Role Of Neonatal NMDA Receptor Activation In Defeminization And Masculinization Of Sex Behavior In The Rat and draw the obvious conclusions.

Conversation Deliberately Skirts The Border Of Incomprehensibility

From lierdumoa.tumblr.com:

To my friends on the [autism] spectrum, let me explain to you an unspoken social rule that possibly nobody has ever explained to you before

If a neurotypical asks you, “What game are you playing?” they’re not asking you to describe the game.

They’re asking you if they can play too.

If a neurotypical asks you, “What are you watching?” they’re not asking you to explain the plot of the movie/tv show to them.

They’re asking if they can watch it with you.

When neurotypicals ask you “What are you doing?”

What you think they’re asking: “Please explain to me what you are doing.”
What they’re actually asking: “Can I join you?”

Now here’s the really fucked up part. If you start explaining to them what you’re doing? They will interpret that as a rejection.

What you think you’re saying: [the answer to their question]
What they think you’re saying: This is an elite and exclusive activity for a level 5 friend and you are a level 1 acquaintance. You are not qualified to join me because you don’t know all this stuff. Go away.

This is why neurotypicals think you’re being cold and antisocial.

IT’S ALL A HORRIBLE MISCOMMUNICATION.

I don’t think this is always true – and when it is I would describe it as more of an open-ended attempt to start a fun conversation than a demand for participation – but I agree that it’s not just a straightforward request for information.

And there was some interesting discussion about this on Autistic Tumblr, which centered around: why would someone do this? Why can’t people just say what they mean?

And the best answer I saw – sorry, I can’t find it right now – explained that people were trying to spare their friends the burden of rejecting them. Say Alice is reading a book, and Bob asks “Hey, do you want to talk about that book?” Maybe Alice doesn’t want to talk about it. But the following conversation…

Bob: Hey, you want to talk to me about that book?
Alice: No

…sounds really rude. So by Bob saying his line, he’s putting a lot of subtle pressure on Alice to agree. Bob is a good person and he doesn’t want to do that. So instead he asks “Hey, what are you reading?”

Bob: Hey, what are you reading?
Alice: Not much. Just some random novel.
Bob: Oh, well, enjoy!

Or:

Bob: Hey, what are you reading?
Alice: Oh! It’s really interesting! It’s this book where Apollo 8 crashes into the celestial sphere surrounding the world, and suddenly everything reverts to kabbalistic Judaism…
Bob: Sounds neat! What happens next?

Here Alice either has an opportunity to signal that she wants to continue the conversation, or to reject Bob while maintaining plausible deniability that she’s doing that.

(The beauty of this theory is ruined only by the fact that half the time this happens in real life and I say “Just some random novel,” Bob actually answers “Oh! What kind of random novel?” and then I say “Oh, nothing really”, and Bob says “Come on! Something has to happen!” and then I start despairing that anything about social interaction can ever work at all. I don’t know. Maybe Bob is autistic.)

What I find interesting about “plausible deniability” explanations is that Bob has to operate as close to the border of “inscrutable confusingness” as possible without crossing it. He wants Alice to know he wants to talk to her, but he doesn’t want Alice to know that he knows she knows he wants to talk to her (I’m being very deliberate in putting the word “know” exactly three times there rather than just using a vague phrase like “common knowledge”). As long as Alice doesn’t know he knows she knows he wants to talk to her, Alice can give a non-answer, pretending that she believes Bob will believe that she just didn’t realize he wanted to talk to her.

And this sort of weird common-knowledge-denial-process only works if you’re skirting the border of incomprehensibility, hitting a sweet spot where you think the other person will understand, but it’s also just barely plausible that the other person wouldn’t understand. If you say something the other person would definitely understand, then the game is up. Given some sort of natural variation in how good people are at understanding cues, your best bet is to send a cue that will fail a small but non-zero percent of the time.

But if there are people who are unusually bad at understanding social cues, like autistic people, then any cue calibrated to be on the exact border of neurotypical understanding is likely to fail for them more often than not.

I don’t know how common this pattern is. Making requests seems like a pretty good example. Flirting seems to be centered upon this kind of thing. I’m not sure what else is involved, but I bet it’s a lot.

A while ago I quoted a paper by Lawson, Rees & Friston about predictive-processing-based hypotheses of autism. They said:

This provides a simple explanation for the pronounced social-communication difficulties in autism; given that other agents are arguably the most difficult things to predict. In the complex world of social interactions, the many-to-one mappings between causes and sensory input are dramatically increased and difficult to learn; especially if one cannot contextualize the prediction errors that drive that learning.

And I was really struck by the phrase “arguably the most difficult thing to predict”. Really? People are harder to predict than, I don’t know, the weather? Weird little flying bugs? Political trends? M. Night Shyamalan movies? And of all the things about people that should be hard to predict, ordinary conversations?

And I think part of the answer might be: ordinary conversations are hard to predict because they’re designed to be so. Conversation norms are anti-inductive. Like Douglas Adams’ conception of the universe, any time people start to understand them too well, they have to get replaced with something a little bit less comprehensible.

To Understand Polarization, Understand Conservativism’s Failures

Earlier today I talked about one reason for increased polarization on the Democratic side. Now I want to match it with one reason the Republicans have even more of a problem.

Ask anyone what Republicans want, and they’ll say things like “smaller government”, “fewer regulations”, and “less welfare state”.

Meanwhile, here are some graphs showing how they’re doing (disclaimer: graphs like this are very dangerous, and I can only plead that I’ve seen numbers like these from enough sources that I think they have some contact with reality):

Source: https://fivethirtyeight.blogs.nytimes.com/2013/01/16/what-is-driving-growth-in-government-spending/

Source: https://regulatorystudies.columbian.gwu.edu/reg-stats

Source: http://www.motherjones.com/kevin-drum/2016/02/heres-why-bernie-sanders-doesnt-say-much-about-welfare-reform/

Apparently not so good.

This is true even though this is a historic apex of Republican power. They control the House, the Senate, the Presidency, 66% of state governorships, 68% of relevant state legislatures, and are kind of tied-ish for control of the Supreme Court. They’ve been two of the last four Presidents, and controlled Congress more often than not during that period.

This is really strange. Whatever they wanted, they should have been able to get. Who’s going to stop them? Democrats? Don’t make me laugh.

But in fact, we mostly kept getting bigger government, more regulations, and a bigger welfare state.

My guess is this is a larger-scale version of what I talked about in Considerations On Cost Disease. Various secular trends make everything more expensive and worse, which means government has to spend more money and regulation to get the same level of services, which means government gets bigger. There’s no easy way to stop this except to understand cost disease (which people don’t) or to drastically cut the level of services and admit it will keep getting worse (which politicians are scared of doing on their watch). This is not really the Republicans’ fault.

But Republican voters don’t know that.

All they see is candidates running for office on a platform of small government and less regulation. Then they win, they’ve got a huge majority and a great mandate, and at the end of their term government is as big as always and there are more regulations than ever.

And if maybe you’re not that sophisticated about these kinds of things, you think – these guys betrayed me. They’re Republicans in name only. They were corrupted by Washington. The liberal media finally got them. They’re weak and they caved as soon as the Democrats called them mean names. What we need are some real Republican candidates, ones who are actually willing to stand up to the establishment.

Then you elect the Real Republican Candidates, the Tea Party or whoever, and the same thing happens. Because we’re talking about secular trends and not about anything that Congress can easily affect.

So then the voters think they’re frauds too, and they get defeated in the primaries by other people who are even more Tea Party than they are, people who can say oh yeah, those Tea Party people were fake, but we have the necessary commitment to go to Washington and not cave in immediately.

This will never work. But the superficial logic of “Republicans are powerful enough to get whatever they want, we don’t have small government, therefore the current crop of so-called Republicans didn’t really want small government enough” is convincing. You end up with a signaling spiral where everyone’s in an arms race to show that they’re not actually the craven compromisers that people will inevitably assume them to be. That means hyperpartisanship and refusal to compromise on anything.

I’m talking about this as a Republican problem, but I think it’s a general issue whenever people have unrealistic expectations, ie always. The more our hopes diverge from the possible, the more we’ll reject all existing governments in favor of stronger and stronger forms of extremism.

Posted in Uncategorized | Tagged | 688 Comments

Against Murderism

[Content warning: discussion of racism. Comments are turned off due to bad experience with the comments on this kind of material.]

I.

A set of questions, hopefully confusing:

Alice is a white stay-at-home mother who is moving to a new neighborhood. One of the neighborhoods in her city is mostly Middle Eastern immigrants; Alice has trouble understanding their accents, and when they socialize they talk about things like which kinds of hijab are in fashion right now. The other neighborhood is mostly white, and a lot of them are New Reformed Eastern Evangelical Episcopalian like Alice, and everyone on the block is obsessed with putting up really twee overdone Christmas decorations just like she is. She decides to move to the white neighborhood, which she thinks is a better cultural fit. Is Alice racist?

Bob is the mayor of Exampleburg, whose bus system has been losing a lot of money lately and will have to scale back its routes. He decides that the bus system should cut its least-used route. This turns out to be a bus route in a mostly-black neighborhood, which has only one-tenth the ridership of the other routes but costs just as much. Other bus routes, most of which go through equally poor mostly-white neighborhoods, are not affected. Is Bob racist?

Carol is a gay libertarian who is a two-issue voter: free markets and gay rights. She notices that immigrants from certain countries seem to be more socialist and more anti-gay than the average American native. She worries that they will become citizens and vote for socialist anti-gay policies. In order to prevent this, she supports a ban on immigration from Africa, Latin America, and the Middle East. Is Carol racist?

Dan is a progressive member of the ACLU and NAACP who has voted straight Democrat the last five elections. He is studying psychology, and encounters The Bell Curve and its theory that some of the difference in cognitive skills between races is genetic. After looking up various arguments, counterarguments, and the position of experts in the field, he decides that this is probably true. He avoids talking about this because he expects other people would misinterpret it and use it as a justification for racism; he thinks this would be completely unjustified since a difference of a few IQ points has no effect on anyone’s basic humanity. He remains active in the ACLU, the NAACP, and various anti-racist efforts in his community. Is Dan racist?

Eric is a restauranteur who is motivated entirely by profit. He moves to a very racist majority-white area where white people refuse to dine with black people. Since he wants to attract as many customers as possible, he sets up a NO BLACKS ALLOWED sign in front of his restaurant. Is Eric racist?

Fiona is an honest-to-goodness white separatist. She believes that racial groups are the natural unit of community, and that they would all be happiest set apart from each other. She doesn’t believe that any race is better than any other, just that they would all be happier if they were separate and able to do their own thing. She supports a partition plan that gives whites the US Midwest, Latinos the Southwest, and blacks the Southeast, leaving the Northeast and Northwest as multiracial enclaves for people who like that kind of thing. She would not use genocide to eliminate other races in these areas, but hopes that once the partition is set up races would migrate of their own accord. She works together with black separatist groups, believing that they share a common vision, and she hopes their countries will remain allies once they are separate. Is Fiona racist?

II.

As usual, the answer is that “racism” is a confusing word that serves as a mishmash of unlike concepts. Here are some of the definitions people use for racism:

1. Definition By Motives: An irrational feeling of hatred toward some race that causes someone to want to hurt or discriminate against them.

2. Definition By Belief: A belief that some race has negative qualities or is inferior, especially if this is innate/genetic.

3. Definition By Consequences: Anything whose consequence is harm to minorities or promotion of white supremacy, regardless of whether or not this is intentional.

Some thoughts:

Definition By Consequences Doesn’t Match Real-World Usage

I know that Definition By Consequences is the really sophisticated one, the ones that scholars in the area are most likely to unite around. But I also think it’s uniquely bad at capturing the way anyone uses the word “racism” in real life. Let me give four examples.

First, by this definition, racism can never cause anything. People like to ask questions like “Did racism contribute to electing Donald Trump?” Under this definition, the question makes no sense. It’s barely even grammatical. “Did things whose consequence is harm minorities whether or not such harm is intentional contribute to the election of Donald Trump?” Huh? If racism is just a description of what consequences something has, then it can’t be used as an causal explanation.

Second, by this definition, many racist things would be good. Suppose some tyrant wants to kill the ten million richest white people, then redistribute their things to black people. This would certainly challenge white supremacy and help minorities. So by this definition, resisting this tyrant would be racist. But obviously this tyrant is evil and resisting him is the right thing to do. So under this definition, good policies which deserve our support can nevertheless be racist. “This policy is racist” can no longer be a strong argument against a policy, even when it’s true.

Third, by this definition, it doesn’t make a lot of sense to say a particular person is racist. Racism is a property of actions, not of humans. While there are no doubt some broad patterns in people, the question “Is Bob racist?” sounds very odd in this framework, sort of like “Does Bob cause poverty?” No doubt Bob has done a few things which either help or hurt economic equality in some small way. And it’s possible that Bob is one of the rare people who organizes his life around crusading against poverty, or around crusading against attempts to end poverty. But overall the question will get you looked at funny. Meanwhile, questions like “Is Barack Obama racist?” should lead to a discussion of Obama’s policies and which races were helped or hurt by them; issues like Obama’s own race and his personal feelings shouldn’t come up at all.

Fourth, by this definition, it becomes impossible to assess the racism of an action without knowing all its consequences. Suppose the KKK holds a march through some black neighborhood to terrorize the residents. But in fact the counterprotesters outnumber the marchers ten to one, and people are actually reassured that the community supports them. The march is well-covered on various news organizations, and outrages people around the nation, who donate a lot of money to anti-racist organizations and push for stronger laws against the KKK. Plausibly, the net consequences of the march were (unintentionally) very good for black people and damaging to white supremacy. Therefore, by the Sophisticated Definition, the KKK marching the neighborhood to terrorize black residents was not racist. In fact, for the KKK not to march in this situation would be racist!

So Definition By Consequences implies that racism can never be pointed to as a cause of anything, that racist policies can often be good, that nobody “is a racist” or “isn’t a racist”, and that sometimes the KKK trying to terrorize black people is less racist than them not trying to do this. Not only have I never heard anyone try to grapple with these implications, I see no sign anyone has ever thought of them. And now that I’ve brought them up, I don’t think anyone will accept them as true, or even worry about the discrepancy.

I think this is probably because it’s a motte-and-bailey, more something that gets trotted out to win arguments than anything people actually use in real life.

Definition By Belief Is A Mess

Is it racist to believe that Mexicans are poorer than white people? After all, being poor is generally considered bad, so you’re attributing a bad quality to a minority group. What if you add “Mexicans are only poor because of being oppressed and discriminated against?”

Is it racist to believe that Mexicans are more criminal than white people? What if you add “Mexicans are only criminal because their culture was shaped by the experience of oppressive Spanish colonization, which left deep scars on their national psyche”?

Is it racist to believe that Muslims commit more terrorism than white people? What if you’ve done a lot of calculations of per capita terrorist attacks and you can quote exact numbers that prove your point?

Is it more or less racist if then you add “…but this is because Islam is a violent religion that encourages murder, and has nothing to do with the genetics of Middle Eastern people”?

Is it racist to believe that Pygmies are shorter than white people?

But None Of That Really Matters, Because In Real Life, Definition By Motive Usually Trumps Definition By Belief

After the London attacks, I heard someone ask “Do you have to be a racist to want to restrict immigration from Muslim countries? Or can you just be really worried about the terrorism risk?”

A lot of people responded. Some of them said no, it was perfectly reasonable to be worried about terrorism. Other people said that concern about terrorism was just a smokescreen, that people said they were just concerned about terrorism, but actually that was just a way to cover up their racism.

Think about how confusing this is. It’s positing two different things. First, a belief that Muslims are often terrorists and so we should crack down on them. And second, racism. These things are considered opposing explanations, such that if we believe the first one, we can dismiss the second – or, if we admit the second, that proves the first was claimed dishonestly. Under Definition By Belief, it’s really weird.

(compare: “I believe Jesus Christ is the Son of God and those who believe in Him gain eternal life.” “No, you’re just using that as a smokescreen to cover up that you’re Christian!”)

The only way I can make sense of this argument is to think of it as Definition By Motive trumping Definition By Belief. The first person is stating a belief that Muslims are more likely to be terrorists. The second person is questioning whether their motivation for restricting immigration is really this belief (in which case it would be ok) or if they’re motivated by an irrational hatred of minorities (in which case it would be racism).

Definition By Motive can even trump Definition By Belief when we’re talking about innate/genetic difference. Consider Charles Murray saying that he believes black people are genetically less intelligent than white people. Some of Murray’s critics object that this should be suppressed, even if true, because it could be used to justify racism.

Under Definition By Belief, this makes no sense. Imagine Murray was a geologist, pointing out that Antarctica contained mostly sedimentary rock. His critics object “This should be suppressed, even if true, because it could be used to justify believing that Antarctica contains mostly sedimentary rock!” Huh?

It makes more sense if we think of it as being about Definition By Motive. Then the critics are saying that if we find that minority groups are genetically worse in some way (ie racist beliefs are true), we should suppress that lest it be used to justify people’s irrational feelings of hatred for members of other races (ie justify racist motives).

Definition By Motive Makes Sense Of All Of The Above Examples And Basically Matches Most Real-World Usage

Definition By Motive fits the first example. When we ask “Was racism responsible for Trump’s election?” we mean “Did people elect Trump because they irrationally hated minorities and wanted to discriminate against them?”

It fits the second example. When we say that it wouldn’t be racist to resist a tyrant who wants to kill whites, we mean that such resistance is a good policy, which would be pursued for reasons other than just irrationally hating minorities and wanting to discriminate against them.

It fits the third example. When we claim a specific person (Bob, Barack Obama) is racist, we mean that they irrationally hate minorities and want to discriminate against them.

It fits the fourth example. When we say that the KKK marching through a black neighborhood to terrorize people is racist regardless of its consequences, we mean that it’s motivated by an irrational hatred of minorities and desire to discriminate against them.

It fits the fifth example. When we ask whether it’s racist to believe Mexicans are poorer than whites, we’re asking whether someone would only say that because they irrationally hate Mexicans and want to discriminate against them. But most of the time people making that claim are trying to point out inequalities and help Mexicans. So it isn’t racist.

It fits the sixth example. Somebody who believes that Mexicans are more criminal than white people might just be collecting crime stats, but we’re suspicious that they might use this to justify an irrational hatred toward Mexicans and desire to discriminate against them. So it’s potentially racist, regardless of whether you attribute it to genetics or culture.

It fits the seventh example. It’s probably not racist to believe that Muslims commit more terrorism than white people, since this seems to be a true or at least plausible claim, but if people talk about it too much it’s worrying that maybe they’re trying to justify their irrational hatred of Muslims and desire to discriminate against them.

It fits the eighth example. It’s probably not racist to believe that Pygmies are shorter than white people, because it’s obviously true and you would believe it whether you had an irrational hatred of Pygmies or not. Also, no one cares how tall anybody is.

It fits the ninth example. When people ask whether immigration restricts are really due to fear of terrorism vs. racism, they’re asking whether people who claim to be concerned with terrorism actually just irrationally hate minorities and want to discriminate against them.

And it fits the tenth example. When people say that Charles Murray’s claims about genetics might be used to “justify racism”, they mean that if you irrationally hate minorities and want to discriminate against them, you could use his claims about genetics as a justification for why your position makes sense.

Overall We Probably Use A Combination Of All Of These, Weighted In Favor Of Definition By Motives

I designed the discussion questions to be situations where Definition By Motive clearly didn’t apply, but one or both of the other definitions clearly did. I imagine some people stuck to their guns, went Definition By Motive all the way through, and said none of the people in the vignettes were racist. I imagine other people used one of the other two definitions, or a different definition of their own, and were able to navigate all of the objections and counterexamples down here in Part II successfully. But I think most people found a couple of inconsistencies, aren’t really sure what to do with them, and are just sort of echoing the Supreme Court’s view of pornography: “I’ll know it when I see it.”

This is natural. I’m not trying to say that Definition By Motives is the one “real” definition. All of our word usage is a mess; we hardly ever use anything simply or consistently, let alone a complicated word like “racism”. In reality we go back and forth among all of these, proving that something is racist using one definition, then applying the consequences of another definition, switching from very strict to very loose based on whether or not it’s something we like. All of this is totally normal.

But in this case it’s kind of likely to lead to disaster.

III.

A digression, from an alternative universe.

“Murderism” is the ideology that murdering people is good and letting them live is bad. It’s practically omnipresent: 14,000 people are murdered in the US each year. That’s a lot of murderists, and a testament to the degree to which our schools teach murderist values.

But not all murderism is that obvious. For years, people have been pushing “soft-on-crime” policies that will defund the police and reduce the length of jail sentences – inevitably increasing the murder rate. Advocates of these policies might think that just because they’re not gangsters with knives, they must not be murderists. But anybody who supports murder, whether knife-wielding gangster or policy analyst – is murderist and responsible for the effects of their murderism.

Our two major parties have many differences – but both are united in their support for murderism. Republicans push murderist policies like the invasion of Iraq, which caused the murder of thousands of Iraqis. Democrats claim to be better, but they support openly murderist ideas like euthanasia, promoting the killing of our oldest and most vulnerable citizens. There’s no party in Washington that’s willing to take a good look at itself and challenge the murderist ideals that our political system is built on.

Murderism won’t stop until people understand that it’s not okay to be murderist. So next time you hear people opposing police militarization, or speaking out in favor of euthanasia – tell them that that’s murderism and it’s not okay.

…okay, done. Back in our own universe, we recognize that “murderism” is silly: it confuses cause and effect.

Murder is usually an effect of a strategy pursued for other reasons. The drug dealer who wants to keep rivals off his turf, the soldier who wants to win a war, the gangster who wants to get rid of inconvenient witnesses. If you want to stretch it, add the neocon who wants to “liberate” foreign countries, the cancer patient who wants to “die with dignity”, or the activist who wants to keep people out of jail.

But except in maybe the most deranged serial killers, it’s never pursued because of an inherent preference for murder. Most murderers would probably prefer not to have to kill. If the drug dealer could protect his business equally well by politely requesting people stay off his territory, that would be much easier. If the soldier could win his war without bloodshed, so much the better for everybody. Murder is an effect of other goals – sometimes base, sometimes noble – and the invocation of “murderism” only serves to hide these goals and conflate different actions into a single meaningless category.

Talking about murderism isn’t just uninformative, it’s actively confusing. If you believed that gangsters killed their rivals because of murderism, then there’s no point in examining how poverty interacts with gang membership, or whether the breakdown of law forces people to form gangs to defend themselves. The problem is just that gangsters have murderist values. It should be solved by censoring the works of philosopher David Benatar, who writes about how being alive is bad and it’s morally better not to exist at all. Or by banning high school Goths, whose pro-death aesthetic makes murderism seem cool to teens and causes them to harbor murderist thoughts as adults.

Talk about murderism is obviously confused. But it’s the same confusion between the Definition By Consequences versus the Definition By Motive that we saw was a hallmark of racism.

IV.

Belief in murderism creates a hostile and ineffective society whose weird beliefs can only be countered by accepting that murder is rarely a terminal goal, but a usually result of strategies pursued for other reasons. We accept that having a terminal goal of killing people seems so awful, inhuman, and incongruous with the sort of decent humans we all know – that it’s a very strange explanation to even consider when other, better ones are available. We can apply the same analysis to racism. The discussion questions in Part I already started the process, but we can go further.

I’m not just making the argument “lots of things aren’t really racist”. I can’t do much about how you choose to define words, plus it’s doomed to fail anyway. Imagine having to convince someone that a guy who committed homicide “isn’t really murderist”. Doesn’t sound like the most winnable fight.

And if you only break down non-racist things into non-racist motives, what reward shall you have? Do not even the scribes and the Pharisees do the same? I say unto you, if you want to be righteous, look for the non-racist motives in actually racist things.

What does that mean?

Consider some business, let’s say a daycare center, that we know discriminates against black job-seekers. If we ask them why, they say “Because black people are criminal”. This sounds like just about the most typical and obvious example of racism possible.

But there’s actually a lot of really good scholarship on this exact situation, and it helps provide a different perspective. It starts like this – a while ago, criminal justice reformers realized that mass incarceration was hurting minorities’ ability to get jobs. 4% of white men will spend time in prison, compared to more like 16% of Hispanic men and 28% of black men. Many employers demanded to know whether a potential applicant had a criminal history, then refused to consider them if they did. So (thought the reformers) it should be possible to help minorities have equal opportunities by banning employers from asking about past criminal history.

The actual effect was the opposite – the ban “decreased probability of being employed by 5.1% for young, low-skilled black men, and 2.9% for young, low-skilled Hispanic men.”

In retrospect, this makes sense. Daycare companies really want to avoid hiring formerly-imprisoned criminals to take care of the kids. If they can ask whether a certain employee is criminal, this solves their problem. If not, they’re left to guess. And if they’ve got two otherwise equally qualified employees, and one is black and the other’s white, and they know that 28% of black men have been in prison compared to 4% of white men, they’ll shrug and choose the white guy.

Is this racist? Is this “statistical discrimination”? Describe it with whatever word you want. The point is that they have understandable motives (don’t hire criminals to take care of the kids), accurate beliefs, and in their shoes you might do the same. More important, once you give them the tools they need to solve their problems without racial discrimination – you let them see applicants’ criminal histories – they have no further desire to discriminate and your problem is solved.

If you tried to solve this by sending these people to sensitivity training, you would fail. IF you tried to solve this by firing these people, then the people who replaced them would have the same incentives, and you would fail again. If you try to solve it by realizing that racial animus has no role at all in this scenario, and daycare owners just want to do what’s best for their kids, then you can provide them with the tools they need to do that, and solve the racial discrimination at the same time.

Okay, fine. Harder example. Let’s take, uh, some guy who’s always ranting about how the Jews secretly control the world. They have underground tunnels where they have their secret Zionist meetings and talk about how they’re going to stick it to the Christians. Every major war and economic downturn has been caused by this. Are we allowed to treat this guy‘s racism as being a conceptual primitive that doesn’t need further breaking down?

I actually knew a guy like this. He was a schizophrenic patient in the mental hospital where I work. Overall I found it a nice break from the tedium of CIA-conspiracy folk, alien-conspiracy folk, and white-people-conspiracy folk (remember, this is Detroit).

Am I saying everyone like this is schizophrenic? Not diagnosably, no. But I notice that there are a lot of not-diagnosably-schizophrenic people who believe in the Illuminati, the New World Order, the Freemasons, and – yes – lizardmen. Is it really so outlandish to say that the same faulty reasoning that concludes that Freemasons run the world could conclude that Jews run the world, and for the same reasons? Does it really make sense to just blow one off as paranoid conspiracy-mongering, and the other as originating from a completely different process called “anti-Semitism” or “racism”? Remember, “healthy” people with paranoid and conspiratorial beliefs have the same kind of fronto-striatal prediction error signal that schizophrenics do, only less so, suggesting that their odd ideas probably come from the same kind of disturbed reasoning process.

“Are you saying that anti-Semitism literally plays no role in their theory about the Elders of Zion”? Again, call it what you want. I’m saying that by totally ignoring the anti-Semitic aspect, I was able to successfully treat this guy with Seroquel, whereas if you tried to read him Elie Wiesel books, he’d still be in that psych ward today.

Fine. Schizotypal conspiracy-mongerers are a noncentral example anyway. What about, I don’t know, rural Republicans in South Carolina who wave the Confederate flag all the time and think blacks and immigrants are ruining the country.

Here I would point out that this is pretty much the demographic that elected Nikki Haley (birth name, Nimrata Randhawa; daughter of two Punjabi immigrants) as governor, and that supports her so fervently that she remains one of the most popular politicians in the country. Also the demographic that loved Ben Carson, making him the only candidate to briefly displace Trump for first place in the 2016 Republican primary polls. One plausible explanation is that the South Carolinians don’t like blacks and immigrants because they view them as having foreign values – specifically, Blue Tribe values (it may be relevant here that 90%+ of blacks usually vote Democrat). If someone like Nikki Haley or Ben Carson proves that they share Red beliefs, they become part of the tribe and will be fiercely defended. Maybe this is more like the daycare situation than it looks – people using race as a proxy for something they care about, until they get direct information.

To be clear – I am not saying that racism doesn’t exist, I’m not saying that we should ignore racism, I’m not saying that minorities should never be able to complain about racism. I’m saying that it’s very dangerous to treat “racism” as a causal explanation, that it might not tell you anything useful about the world, and that’s a crappy lever to use if you want to change behavior.

And I’m not saying that it’s not useful to think of some of these things as places where there’s an opportunity for racial change. If a daycare owner is really interested in redressing racial inequality, they can hire minorities even if it’s against their incentives and self-interest (although it’s unclear why the owner should prefer that opportunity to other opportunities, like donating some of their profits to the NAACP.)

And I’m not saying that there will never be a case that’s impossible to break down into non-racist motives. Heck, I’m not even saying there aren’t some honest-to-goodness murderists out there. But I am saying we should at least try. Not because it’s necessarily costless. Not because there isn’t a risk of false negatives.

We should try because it’s the only alternative to having another civil war.

V.

Arnold Kling likes to talk about how political groups are divided by different “languages”, different schemata for understanding the world that make it difficult to talk across political divides.

Jonathan Haidt accepts the premise but challenges the symmetry; his experiments ask liberals and conservatives to fill out questionnaires about their values, then to predict how someone from the opposite tribe would fill out the questionnaire. He finds that conservatives are able to predict liberals’ answers just fine and seem to have a pretty good understanding of their worldviews, but that liberals have no idea how conservatives think or what they value.

James Scott, as channeled by Lou Keep, draws the asymmetry a little differently. He says that the process of development, especially state-building and the switch from traditional to market economies, creates a pressure for “legible” language that renders entire classes of problems very difficult to talk about. This creates an asymmetry between an elite plugged into the global market structure whose concerns make perfect sense (“If we do this, GDP will go up 3% and we can build more roads!”) and the masses left behind whose concerns seem pointless and vague (“I feel like something important disappeared when we turned everything into a commodity”). Keep then proposes a very loose mapping onto cosmopolitan neoliberal Clintonites versus undereducated “I’m angry about losing my traditional culture” Trumpists.

There are a bunch more frameworks like this, but they all share the common warning that cross-cultural communication is really hard, and so a lot of the concerns of people who aren’t like us will probably sound like nonsense. And most of them say that our demographic – well-educated people proud of our commitment to logic and reason – are at especially high risk of just dismissing everyone else as too dumb to matter. The solution is the same as it’s always been: hard work, renewed commitment to liberal values, and a hefty dose of the Principle of Charity.

Racism-as-murderism is the opposite. It’s a powerful tool of dehumanization. It’s not that other people have a different culture than you. It’s not that other people have different values than you. It’s not that other people have reasoned their way to different conclusions from you. And it’s not even that other people are honestly misinformed or ignorant, in a way that implies you might ever be honestly misinformed or ignorant about something. It’s that people who disagree with you are motivated by pure hatred, by an irrational mind-virus that causes them to reject every normal human value in favor of just wanting to hurt people who look different from them.

This frees you from any obligation to do the hard work of trying to understand other people, or the hard work of changing minds, or the hard work of questioning your own beliefs, or the hard work of compromise, or even the hard work of remembering that at the end of the day your enemies are still your countrymen. It frees you from any hard work at all. You are right about everything, your enemies are inhuman monsters who desire only hatred and death, and the only “work” you have to do is complain on Twitter about how racist everyone else is.

And I guess it sounds like I’m upset that we’re not very good at solving difficult cross-cultural communication problems which require deep and genuine effort to understand the other person’s subtly different value system. I’m not upset that we can’t solve those. Those are hard. I’m upset because we’re not even at the point where someone can say “I’m worried about terrorism,” without being forced to go through an interminable and ultimately-impossible process of proving to a random assortment of trolls and gatekeepers that they actually worry about terrorism and it’s not just all a ruse to cover up that they secretly hate everyone with brown skin. I’m saying that when an area of the country suffers an epidemic of suicides and overdoses, increasing mortality, increasing unemployment, social decay, and general hopelessness, and then they say they’re angry, we counter with “Are you really angry? Is ‘angry’ just a code word for ‘racist’?” I’m saying we’re being challenged with a moonshot-level problem, and instead we’re slapping our face with our own hand and saying “STOP HITTING YOURSELF!”

People talk about “liberalism” as if it’s just another word for capitalism, or libertarianism, or vague center-left-Democratic Clintonism. Liberalism is none of these things. Liberalism is a technology for preventing civil war. It was forged in the fires of Hell – the horrors of the endless seventeenth century religious wars. For a hundred years, Europe tore itself apart in some of the most brutal ways imaginable – until finally, from the burning wreckage, we drew forth this amazing piece of alien machinery. A machine that, when tuned just right, let people live together peacefully without doing the “kill people for being Protestant” thing. Popular historical strategies for dealing with differences have included: brutally enforced conformity, brutally efficient genocide, and making sure to keep the alien machine tuned really really carefully.

And when I see someone try to smash this machinery with a sledgehammer, it’s usually followed by an appeal to “but racists!”

You say we must protect freedom of speech. But would you protect the free speech of racists?

You say people shouldn’t get fired for personal opinions that don’t affect their work. But would you let racists keep their jobs?

You say we try to solve disagreements respectfully through rational debate. But would you try to rationally debate racists?

You say people should be allowed to follow their religion without interference. But what if religion is just a cover for racism?

You say we need to understand that people we disagree with can sometimes have some good points. Are you saying we should try to learn things from racists?

You say there’s a taboo on solving political disagreements by punching people. Are you saying that we can’t punch racists?

The argument goes: liberalism assumes good faith and shared values. It assumes that, at the end of the day, whether you’re Catholic or Protestant, you can still be a basically good person. You can compartmentalize a few special beliefs relating to the Pope, and your remaining differences can be dissolved by the universal solvent of Reason. After everyone does this, you can invoke the wisdom of crowds via a popular election, and even if you don’t like the results you can at least understand where the other side is coming from. Some people prefer liberty to safety, other people prefer safety to liberty, but if the voters choose the wrong one then at least they’ve erred in an understandable way by preferring one real value to another.

But if there’s some group out there who aren’t connected to normal human values at all, some group that’s deliberately rejected reason; if they’re willing to throw liberty and safety under the bus in pursuit of some kind of dark irrational hatred which is their only terminal goal – then the whole project falls apart. Dialogue based on mutual trust may be all nice and well when it’s supposed to help us choose the optimal balance between liberty and safety, but if you give a platform to the people whose only value is hatred, then they’re just screwing over everybody.

A few days ago, Noah Smith posted on Twitter about hearing some people say racist things. The comments went like this:

Ah well. They said a racist thing. Guess we’ve got to kill them.

And I agree with this chain of logic. Using violence to enforce conformity to social norms has always been the historical response. We invented liberalism to try to avoid having to do that, but you can’t liberalism with people who refuse reason and are motivated by hatred. If you give the franchise to green pointy-fanged monsters, they’re just going to vote for the “Barbecue And Eat All Humans” party. If such people existed and made up a substantial portion of the population, liberalism becomes impossible, and we should go back to just using violence to enforce our will on the people who disagree with us. Assuming they don’t cooperate with our strategy of violently suppressing them, that means civil war.

I don’t want civil war. I want this country to survive long enough to be killed by something awesome, like AI or some kind of genetically engineered superplague. Right now I think going out in a neat way, being killed by a product of our own genius and intellectual progress – rather than a product of our pettiness and mutual hatreds – is the best we can hope for. And I think this is attainable! I think that we, as a nation and as a species, can make it happen.

But it starts with rejecting the “murderism” framework. Rejecting the choice to attribute whatever we disagree with to murderism, even if it is murderist, and instead trying to trace it back to root causes that make sense that and humanize the people involved. Working to find the reasons liberalism is possible, rather than the reasons it isn’t. Unless we can do that, semantic confusion and our political polarization are going to build off each other in a vicious cycle into who knows where.

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OT78: Oprah Thread

This is the bi-weekly visible open thread. Post about anything you want, ask random questions, whatever. You can also talk at the SSC subreddit, the SSC Discord server, or the Cafe Chesscourt forum.

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Links 6/17: Silinks Is Golden

Did you know: JRR Tolkien’s great granddaughter, Ruth Tolkien, is the only blind person in the UK to be a competitive fencer. She is currently ranked the #186th best fencer in the country.

Alpha – an ambiguously-AI-automated alliterative account about abiogenesis. As an annotator already announced, “absolutely an amazing achievement”.

In response to my Silicon Valley reality check, Noah Smith looks for good critiques of Silicon Valley.

Sarah C is interested in a potential sepsis cure and pleads for you to consider helping a hospital fund a study. Outside my area of expertise, except to say that sepsis is really bad and curing it would be pretty great, plus I trust Sarah.

Neerav Kingsland: Ignoring Educational Productivity Is Immoral: “studies consistently find urban charter schools outperform traditional public schools while spending around 20% less per-pupil…what, as a society, could we do with this 20% extra funding that urban charter schools could save us?” I would love to see a debate between Neerav Kingsland and Freddie deBoer – I can host or otherwise try to make it happen if they agree.

Related – Wanted: A Charter High School That Starts Class At A Reasonable Hour

New front on the battle to prove that zero-calorie sodas must be bad in some way: does CO2 in carbonated beverages induce ghrelin release and increase food consumption?

According to Muslim legend, the Jews will try to hide behind trees to escape the Last Judgment, but the trees will shout “There is a Jew behind me, come and kill him!” – except for the Gharqad tree, which is apparently pro-Jew. This has led to all sorts of amazing conspiracy theories, like that Israel is planting a bunch of Gharqad trees to ensure hiding places for its citizens. And here’s a book about Hamas terrorists with an interesting passage on the Gharqad tree legend.

A paper claims that housing restrictions have “lowered aggregate US growth by more than 50% from 1964 to 2009″.

Explaining The Gender Gap In Crime: The Role Of Heart Rate. “A low resting heart rate is widely regarded as the best-replicated biological correlate of antisocial and criminal behavior” Apparently it might have to do with something general level of autonomic arousal being lower in (to be blunt about it) emotionless sociopaths?

The best Internet responses to Trump touching a glowing orb in Saudi Arabia.

I don’t have a source for this, but it looks right, and it’s a really cool way of presenting the data:

The mathematics of Girih tiles, a beautiful form of Islamic art which applied principles of Penrose tilings five hundred years before it was discovered in the West.

Vox tries its hand at an explainer about the Sam Harris / Charles Murray interview. Some criticism from Gene Expression, The Misrepresentation Of Genetic Science In The Vox Piece On Race And IQ. From Elan, The Cherry-Picked Science In Vox’s Charles Murray Article. From Sam Harris, an accusation that the article just blatantly lies about the contents of the publicly available podcast (one of the authors later apologizes for this, but Vox hasn’t changed the article). From Professor Emeritus Richard Haier, who called it a “junk science piece” and tried to write a counterpiece for Vox (they refused to publish it, but it’s now up on Quillette). And even from other Vox reporters who thought it was journalistically shoddy. As for me, I think the article was as good as it could be under the circumstances – while it does get some things wrong and is personally unfair to Murray, from a scientific point of view I’m just really glad that the piece admits that IQ is real, meaningful, and mostly hereditary. This was the main flashpoint of the original debate twenty-five years ago, it’s more important than the stuff on the achievement gap, and the piece gets it entirely right. I think this sort of shift from debating the very existence of intelligence to debating the details is important, very productive, and worth praising even when the details are kind of dubious. This should be read in the context of similar recent articles like NYMag’s Yes, There Is A Genetic Component To Intelligence and Nature’s Intelligence Research Should Not Be Held Back By Its Past.

AskHistorians: Did Roman legionnaires get PTSD? “For the Romans, people experiencing intrusive memories were said to be haunted by ghosts…those haunted by ghosts are constantly depicted showing many symptoms which would be familiar to the modern PTSD sufferer.”

Somehow I went through medical school without ever learning that going in hot tubs while pregnant can be a risk factor for birth defects.

Like a food blog, except it’s RPG rations for dwarves, elves, orcs, et cetera.

Highly educated people are more likely to get brain tumors. The article mentions the boring hypothesis that they just have better access to medical care (but then how come most other cancers are higher in the uneducated?), but also proposes the much more interesting hypothesis that “having more brain cells or greater brain activity somehow increases a person’s risk”.

Future of Humanity Institute in Oxford is looking for a research assistant for Toby Ord (founder of effective altruism, currently working on a book on existential risks). If you’re interested, check out the job details and contact info.

According to the Guinness Book Of World Records, the most fraudulent election in history was the 1927 Liberian presidential contest, in which incumbent Charles King received 234,000 votes despite there being only 15,000 registered voters.

The “moderate drinking increases lifespan” vs. “that’s obviously just a confounder based on only healthy people drinking” wars continue, with the latest volley being that fruit flies and chickens exposed to alcohol vapor live longer. I was previously on the “obviously just a confounder” side of the debate, but the animal studies sound pretty convincing.

Rudyard Kipling, H.G. Wells, Arthur Conan Doyle, P.G. Wodehouse, G.K. Chesterton, and A. A. Milne all played on the same amateur cricket team. The team called themselves the Allahakbarries “[under] the mistaken belief that Allahu akbar meant ‘Heaven help us’ in Arabic.”

Heredity watch: Elon Musk’s maternal grandparents were well-known pilots and explorers, and Musk’s mother spent part of her childhood on various family expeditions in search of a lost city in the Kalahari Desert.

The best new blog I’ve come across recently is Sam[]zdat, which among other things has been reviewing various great books. Their Seeing Like A State review is admittedly better than mine, but I most appreciated The Meridian Of Her Greatness, based on a review of Karl Polanyi’s The Great Transformation. Go for the really incisive look at important ideas and social trends, stay for the writing style.

What lesson should we draw about Democrats’ prospects from the Republicans’ 7 point win in the Montana special election? (point, counterpoint).

The Less Wrong Wiki hosts a List of Rationalist Podcasts.

Behavioral Individuality In Clonal Fish Arises Despite Near-Identical Rearing Conditions. Worth interpreting in the context of my post Non-Shared Environment Doesn’t Just Mean Schools And Peers – even fish raised in exactly the same environments will show “non-shared environment” effects, probably because of something like embryogenetic randomness.

An easier way to read the Less Wrong Sequences online at readthesequences.com.

Mark Zuckerberg Calls For Universal Basic Income In His Harvard Commencement Speech. Sure, Silicon Valley people call for lots of things, but this seems especially important insofar as Zuckerberg seems like he’s positioning himself to run for President at some point.

An analysis showing Donald Trump’s speech patterns getting less fluent and more bizarre over the past few years – might he be suffering from mild age-related cognitive impairment? Also, given that this can be pretty subtle (cue joke about Trump) and affect emotional stability in complicated ways, should we be more worried about electing seventy-plus year old people to the presidency?

A sobering statistic on the difficulty of dialing back mass incarceration (incompletely sourced, but seems to check out): “if America only jailed murderers and rapists, it would still have more prisoners per capita than Western Europe”.

Measures Of Dogs’ Inhibitory Abilities Do Not Correlate Across Tasks. A lot of good cognition studies are being done on dogs these days; this one suggests that we don’t yet have a good general concept of “inhibition” that we can use to say that some animals (people?) have better self-control in general than others.

Big systematic review and meta-analysis: what actually helps lower-income students succeed? Read the paper or the Freddie deBoer blog post, which summarizes the results as “human beings”.

A more recent study on the evolutionary history of Ashkenazi genetic diseases (paper, popular article) claims that Tay-Sachs is probably the result of evolutionary selection, but that others (eg Gaucher, torsion dystonia, Fanconi anaemia, etc) aren’t, which would be a partial blow for Cochran et al’s selection theory. My guess is they just don’t have enough power to detect the effects – if this was all random drift, it would be vanishingly unlikely that so many of these diseases end up in the same pathways (eg lysosomal storage). [EDIT: I may be misunderstanding this; it may just mean there’s no net selection even though they’re diseases]

Related: a reader points out this paper on “The Social Construction Of Hungarian Genius”.

PNAS has a good (albeit kind of silly) article on claims that scientific progress has slowed.

This month in insane Twitter drama, for people who have previously made the good choice not to follow insane Twitter drama but want to walk back on it for some reason: will Sam Kriss publicly denounce Zionism? (1, 2, 3). What happens when Jeet Heer tweets “Bernie would have won”? Is Joan Walsh un-woke on Palestine? And apparently there is some kind of Joan Walsh/Katie Halper feud. I realize this sort of stuff seems petty, but it was really helpful in getting me to understand why everyone hates each other, and helped convince me that a lot of things I thought were silly arguments against straw men are actually important arguments against a large contingent of (depressingly) real people.

Parcel sorting facilities in China.

Noah Smith: The US has forgotten how to do infrastructure.

That story about how Gavrilio Princip failed to assassinate Archduke Ferdinand, then went to get a sandwich, then ran into the Archduke just outside the sandwich shop and assassinated him anyway? The Smithsonian says it’s probably false.

Did you know: the ancient Egyptian language of hieroglyphs and Pharaohs survived into modern times as the Coptic language and is still the liturgical language of Coptic churches today. Also, English words derived from Egyptian include “adobe” and “oasis”.

New study finds that growth mindset is not associated with scholastic aptitude in a large sample of university applicants. Particularly excited about this one because an author said that my blog posts about growth mindset inspired the study. I’m honored to have been able to help the progress of science!

Rocket pioneer Wernher von Braun wrote a 1952 sci-fi story about the colonization of Mars, in which the Martian government was led by a President called “the Elon”.

Internet payment processors and payment regulations are terrible and destroying the nootropics industry and probably a bunch of other industries I know less about, part 459401.

ABC News reported that a meat company’s product was disgusting low-quality “pink slime”, and people stopped buying from that meat company. Now the company is suing ABC for $5.7 billion in a lawsuit with the potential to have chilling effects on journalism in general.

I think the Byzantine Empire had the coolest-sounding titles of any civilization, including Grand Logothete and Megaduke.

A deadly fire in an apartment building in London gains an extra layer of horror in the context of this blog post by apartment residents predicting that there is definitely going to be a deadly fire there soon due to apartment management and local government incompetence.

Contra recent thinkpieces about how polls don’t work and psephology is a pseudoscience, on an aggregate level the probabilities from prediction markets have been impressively accurate.

Phone companies were ready to deploy cellular phones since the 1940s – the reason we didn’t get them until the ’80s was government regulators refusing to give them the spectrum space for political reasons.

There’s wide state-by-state variation on the legality of shooting Bigfoot, with Washington calling it a felony and Texas calling it acceptable given that it’s technically “an invasive species”. (h/t Tumblr)

A swarm of 20,000 bees recently descended upon Vox Media’s Manhattan offices, leading to articles like The Swarm Of Bees Outside Vox Media, Explained.

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What Is Depression, Anyway?: The Synapse Hypothesis

I.

The problem with depression research isn’t that we don’t have any leads on what causes depression. It’s that we have so many leads on what causes depression that we don’t know what to do with all of them. For example:

1. Life adversity, like getting fired or breaking up with a partner, can make people depressed. The biological correlate of this seems to be the hypothalamic–pituitary–adrenal axis (HPA), where your brain tells your adrenal glands to produce glucocorticoid stress hormones like cortisol and this does something to your brain that increases the risk of depression.

2. Inflammation and immune overactivity can make people depressed. The classic examples of this are cancer-related depression (which exceeds what you would expect just from cancer being stressful) and depression induced by administration of the immunomodulator interferon-a. Antiinflammatory drugs have a small but clinically relevant antidepressant effect. Some of the relevant chemicals here seem to be TNF-A and IL-1; these do something to your brain that increases the risk of depression.

3. Serotonin and other monoamines seem to be involved. Most existing antidepressants, like SSRIs and MAOIs, seem to work by increasing monoamine levels. There are some conditions which affect monoamine levels and also increase risk of depression, though it’s nothing like a perfect correlation.

4. The glutamate system (eg NMDA and AMPA receptors) seem to be involved. Ketamine acts on both of these receptors in different ways, and one of those actions is the source of its rapid and unprecedented antidepressant effects.

5. There’s some kind of important link between depression and folate balance. Various folate-related chemicals (eg l-methylfolate and s-adenosylmethionine) are effective antidepressants. Some studies show that people with depression sometimes have disrupted folate cycles, for example elevated homocysteine levels.

6. Electroconvulsive therapy (“shock therapy”) is very effective at treating depression if it induces a seizure in the patient, so the increased activity from seizures must be helpful somehow.

So if we wanted to know what depression really was, it might be promising to look for some process that seems to match depressive symptoms and affects/is affected by life adversity, inflammation, monoamines, glutamate, folate, and electricity.

Recently some people think they’ve found one. According to Duman’s Neurobiology of Stress, Depression, and Rapid Acting Antidepressants, it’s decreased synaptogenesis, and it’s regulated by a protein complex called mTORC1.

Neurons communicate with other neurons through branches called dendrites and connections called synapses. Healthy neurons often create new dendrites and synapses to expand their network of connections and adjust to new information. The process of making new synapses is called “synaptogenesis”, and it’s common throughout the adult brain.

As mentioned above, depressed people have decreased volume in some brain areas. But in postmortem studies, they don’t actually have fewer cells in those areas. So it looks like maybe these neurons just have less synaptogenesis going on.

Synaptogenesis is partly controlled by a protein complex called mechanistic target of rapamycin complex 1 (mTORC1 to its friends). Like every other protein, mTORC is controlled by a giant mess of receptors and second messengers and intracellular signals with names like VDCC and GSK3.

People try to make this seem simple by displaying it as a system of billiard balls and tubes in a cute cartoon, but don’t be fooled – no human being has ever remembered any of it for more than two seconds.

The factors that affect synaptogenesis and mTORC are many of the same factors that affect depression. Let me count the ways:

1. Life adversity causes chronic stress, biologically represented by upregulation of the HPA axis and increased corticosteroid production. A 2008 study finds that rats who are subjected to chronic stress develop atrophy of dendrites in their prefrontal cortex. Administering glucocorticoids directly mimicked some of these effects, suggesting that stress is a whole cocktail of things including glucocorticoids and other things. When humans take glucocorticoids (they’re a useful medicine for various diseases) they tend to develop hippocampal atrophy and “simplification of dendrites” there, which I think is the same as decreased synaptogenesis. They also tend to get depressed – in some studies of Cushing’s Syndrome (the medical name for the collection of bad things that happen when you take too much glucocorticoid medication), up to 90% of patients are depressed.

2. I didn’t find the linked paper’s attempt to link inflammation to synaptogenesis very convincing, but it looks like there’s a little bit of research that has found that systemic inflammation decreases synaptogenesis. “Morphometric analysis of dendritic spines identified a period of vulnerability, manifested as a decrease in [dendritic] spine density in response to inflammation. The density of presynaptic excitatory terminals was similarly affected. When the systemic inflammation was extended from 24h to 8 days, the negative effects on the excitatory terminals were more pronounced and suggested a reduced excitatory drive.” This seems pretty relevant.

3. Everyone used to think that traditional antidepressants like SSRIs worked by increasing serotonin (and so by extension depression must have something to do with low serotonin levels). But SSRIs increase serotonin very quickly (within hours) yet take months to work. Something longer-term must happen when serotonin levels have been increased for long enough. That something has now been pretty conclusively identified as an increase in brain-derived neurotrophic factor (BDNF) – although I can’t find any good explanation of why increased serotonin should cause increased BDNF after a month. BDNF is a nerve growth factor – its main action is activating mTORC and telling nerve cells to grow more dendrites and synapses. And it’s most active in the cortex and hippocampus.

4. Ketamine affects the brain by either blocking NMDA receptors (boring traditional explanation), activating AMPA receptors (exciting new explanation), or possibly both (wishy-washy neoliberal compromise explanation). Duman et al are kind of ambiguous about which explanation they accept, but I think they present a theory where NMDA blockade causes AMPA activation, or something, which I’d never heard before. In any case, they present ample evidence that AMPA rapidly affects BDMF and dendritogenesis – for example, Positive AMPA Receptor Modulation Rapidly Stimulates BDNF Release And Increases Dendritic MRNA Translation. The “rapidly” part is important – the surprising thing about ketamine is how quickly it works compared to other antidepressants, so it’s exciting to find a theory that predicts this should happen.

5. I haven’t seen much attempt to fit folate into this theory, which is a shame. A quick Google search brings up a few people talking about how folate deficiency decreases neurogenesis in the hippocampus, which is sort of related.

6. Studies show that ECT increases BDNF levels and increases hippocampal volume, though I’m not sure exactly how or why giving someone a seizure should do that.

So the synapse hypothesis can unify at least five of the six lines of research into the causes of depression.

II.

My remaining skepticism is mostly based on a worry that anyone can do this with anything. The body is so interconnected, and there’s so much bad biology research out there, that I worry that if I said that the real cause of depression was, uh, thickness of the blood, I could find some way that all of those lines of research above affected blood thickness.

A quick demonstration: glucocorticoids can cause thicker blood, inflammation can cause thicker blood, SSRIs cause thinner blood, folate causes thinner blood. Huh, actually that’s kind of creepy.

My point isn’t that the (very respectable) academic research on depression is anywhere near this silly. It’s just to explain why I can hear a theory that seems to explain everything beautifully and my only reaction is “Eh, sounds like it has potential, let’s see what happens.”

Here are some of the things that confuse me, or that I hope get researched more in the future:

1. Why should decreased synaptogenesis cause depression, of all things? If you asked me, a non-neuroscientist, to guess what happens if the brain can’t create new synapses very well and loses hippocampal volume, I would say “your memory gets worse and you stop being able to learn new things”. But this doesn’t really happen in depression – even the subset of depressed people who get cognitive problems usually just have “pseudo-dementia” – they’re too depressed to put any effort into answering questions or doing intelligence tests. Why should decreased synaptogenesis in the hippocampus and prefrontal cortex cause poor mood, tiredness, and even suicidality? All that the Duman et al paper has to say about this is:

This reduction in dendrite complexity and synaptic connections could contribute to the decreased volume of PFC and hippocampus observed in depressed patients. Moreover, loss of synaptic connections could contribute to a functional disconnection and loss of normal control of mood and emotion in depression (Fig. 1). In particular, the medial PFC exerts top down control over other brain regions that regulate emotion and mood, most notably the amygdala, and loss of synaptic connections from PFC to this and other brain regions could thereby result in more labile mood and emotion, as well as cognitive deficits.

…which sounds more like an IOU for a theory than anything really fleshed out.

2. Why can’t we just give people BDNF for depression? I’ve been looking into this and it seems like the answer is something like “this works great if you cut open someone’s skull and inject it directly into their brain, but most people aren’t up for it” (the relevant studies were done in rats). But why can’t it be given peripherally? Some studies suggest it’s stable on injection and crosses the blood-brain barrier. Some people tried this in mice and got modest results, but why aren’t people looking into it more?

3. Why does the body have so many “decrease synaptogenesis” knobs? That is, why go through the trouble to evolve all these chemicals and systems whose job is to tell your brain to decrease synapse formation so much that you end up depressed? Is there some huge problem with having too much synapse formation which the brain is desperately trying to avoid? For that matter, what is it like to have too much synapse formation? If it’s the opposite of depression, it sounds kind of fun. If I got someone to open up my skull and inject a lot of BDNF, could I be really happy and energetic all the time? How come all the good stuff is always reserved for rats?

4. Why is depression an episodic disease? That is, how come so many people get depressed for no reason, stay depressed for a few months to a few years, and then get better – only to relapse back into depression a few years later? If people get depressed because of some life stressor like a divorce, how come they don’t get un-depressed once the life stressor goes away? Is depression some kind of attractor state? If so, why?

5. Why doesn’t rapamycin cause depression? Remember, mTORC is “mechanistic target of rapamycin”, so named because the drug rapamycin inhibits it. But we give people rapamycin for various things all the time, and depression isn’t really known as a major side effect (even though IIRC it crosses the blood-brain barrier). If depression is really under the immediate control of mTORC, rapamycin should be the most depressive thing. Instead it’s not obviously depressive at all.

6. How does bipolar disorder fit into all of this? Is mania the answer to my “what is it like to have too many synapses?” question from point (3)? If so, why do some people go back and forth between that and depression?

A lot of these questions could be answered in one stroke if we had a good evolutionary theory of depression. I’m skeptical that this exists – depression just seems too fitness-decreasing, and the various just-so stories people have come up with for why it might increase fitness in certain weird situations seem a little too convoluted. So it’s not that I’m expecting some sort of evolutionary story to work out. Just noticing that, even if the synapse theory of pathophysiology turns out to be right, there’s still a lot more that needs to be explained.

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