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Is psychosis an ‘immune disorder’?

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A fascinating new study has just been published which found evidence for the immune system attacking a neuroreceptor in the brain in a small proportion of people with psychosis. It’s an interesting study that probably reflects what’s going to be a cultural tipping point for the idea of ‘immune system mental health problems’ or ‘madness as inflammation disorder’ but it’s worth being a little wary of the coming hype.

This new study, published in The Lancet Psychiatry, did blood tests on people who presented with their first episode of psychosis and looked for antibodies that attack specific receptors in the brain. Receptors are what receive neurotransmitters – the brain’s chemical signals – and allow information to be transferred around the nervous system, so disruption to these can cause brain disturbances.

The most scientifically interesting finding is that the research team found a type of antibody that attacks NMDA receptors in 7 patients (3%) out of 228, but zero controls.

The study found markers for other neuroreceptors that the immune system was attacking, but the reason the NMDA finding is so crucial is because it shows evidence of a condition called anti-NMDA receptor encephalitis which is known to cause episodes of psychosis that can be indistinguishable from ‘regular’ psychosis but for which the best treatment is dealing with the autoimmune problem.

It was only discovered in 2007 but there has been a long-running suspicion that it may be the best explanation for a small minority of cases of psychosis which can be easily misdiagnosed as schizophrenia.

Importantly, the findings from this research have been supported by another independent study that has just been published online. The two studies used different ranges for the concentration of NMDA antibodies they measured, but they came up with roughly the same figures.

It also chimes with a growing debate about the role of the immune system in mental health. A lot of this evidence is circumstantial but suggestive. For example, many of the genes associated (albeit weakly) with the diagnosis of schizophrenia are involved in the immune system – particularly in coding proteins for the major histocompatibility complex.

However, it’s worth being a little circumspect about this new enthusiasm for thinking of psychosis as an ‘immune disorder’.

Importantly, these new studies did blood tests, rather than checking cerebrospinal fluid – the fluid that your brain floats around in which lies on the other side of the blood-brain barrier, so we can’t be sure that these antibodies were actually affecting the brain in everyone found to have them. It’s likely, but not certain.

Also, we’re not sure to what extent anti-NMDA antibodies contribute to the chance of developing psychosis in everyone. Certainly there are some cases where it seems to be the main cause, but we’re not sure how that holds for all.

It’s also worth bearing in mind that the science over the role of the genes associated with the schizophrenia diagnosis in the immune system is certainly not settled. A recent large study compared the role of these genes in schizophrenia to known autoimmune disorders and concluded that the genes just don’t look like they’re actually impacting on the immune system.

There’s also a constant background of cultural enthusiasm in psychiatry to identify ‘biomarkers’ and anything that looks like a clear common biological pathway even for a small number of cases of ‘psychiatric’ problem gets a lot of airtime.

Curiously, in this case, Hollywood may also play a part.

A film called Brain On Fire has just been shown to film festivals and is being tested for a possible big release. It’s based on the (excellent) book of the same name by journalist Susannah Cahalan and describes her experience of developing psychosis only for it later to be discovered that she had anti-NMDA receptor encephalitis.

Hollywood has historically had a big effect on discussions about mental health and you can be sure that if the movie becomes a hit, popular media will be alive with discussions on ‘whether your mental health problems are really an immune problem’.

But taking a less glitzy view, in terms of these new studies, they probably reflect that a small percentage of people with psychosis, maybe 1-2%, have NMDA receptor-related immune problems that play an important role in the generation of their mental health difficulties.

It’s important not to underestimate the importance of these findings. It could potentially translate into more effective treatment for millions of people a year globally.

But in terms of psychosis as a whole, for which we know social adversity in its many forms plays a massive role, it’s just a small piece of the puzzle.
 

Link to locked Lancet Psychiatry study.




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nikolap
2 days ago
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Zagreb, Croatia
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When Einstein Tilted at Windmills - Issue 43: Heroes

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When they met, Einstein wasn’t Einstein yet. He was just Albert Einstein, a kid, about 17, with a dark cloud of teenage angst and a violin. Michele Besso was older, 23, but a kindred spirit. Growing up in Trieste, Italy he had shown an impressive knack for mathematics, but he was kicked out of high school for insubordination and had to go live with his uncle in Rome. Einstein could relate. At the Swiss Polytechnic, where he was now a student, his professors resented his intellectual arrogance, and had begun locking him out of the library out of spite.

Their first encounter was on a Saturday night in Zurich, 1896. They were at Selina Caprotti’s house by the lake for one of her music parties. Einstein was handsome—dark hair, moustache, soulful brown eyes. Besso was short with narrow, pointed features and a thick pile of coarse black hair on his head and chin. Einstein had a look of cool detachment. Besso had the look of a nervous mystic. As they chatted, Einstein learned that Besso worked at an electrical machinery factory; Besso learned that Einstein was studying physics. Perhaps they recognized something in each other then: They both wanted to…
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nikolap
4 days ago
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Zagreb, Croatia
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SSC Journal Club: Expert Prediction Of Experiments

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I.

It’s been a good month for fretting over failures of expert opinion, so let’s look at DellaVigna & Pope, Predicting Experimental Results: Who Knows What?

The authors ran a pretty standard behavioral economics experiment where they asked people on Mechanical Turk to do a boring task while being graded on speed and accuracy. Then they offered one of fifteen different incentive schemes, like “we’ll pay you extra if you do well” or “your score will be publicly visible”.

But the point of the study wasn’t to determine which incentive scheme worked the best, it would determine who could best predict which incentive scheme worked the best. The researchers surveyed a bunch of people – economics professors, psychology professors, PhD students, undergrads, business students, and random Internet users on Mechanical Turk – and asked them to predict the experimental results. Since this was a pretty standard sort of behavioral economics experiment, they were wondering whether people with expertise and knowledge in the field might be better than randos at figuring out which schemes would work.

They found that knowledgeable academics had some advantage over randos, but with enough caveats that it’s worth going over in more detail.

First, they found that prestigious academics did no better (and possibly slightly worse) than less prestigious academics. Full professors did no better than associate professors, assistant professors, or PhD students. People with many publications and citations did no better than people with fewer publications and citations.

Second, they found that field didn’t matter. Behavioral economists did as well as microeconomists did as well as experimental psychologists did as well as theoretical psychologists. To be fair, this experiment was kind of in the intersection of economics and psychology, so all of these fields had equal claim to it. I would have liked to see some geologists or political scientists involved, but they weren’t.

Third, the expert advantage was present in one measure of accuracy (absolute forecast error), but not in another (rank-order correlation). On this second measure, experts and randos did about equally well. In other words, experts were better at guessing the exact number for each condition, but not any better at guessing which conditions would do better or worse relative to one another.

Fourth, the expert advantage was pretty small. Professors got an average error of 169, PhD students of 171, undergrads of 187, MBA students of 198, and MTurk users of 271 (random guessing gave an error of about 416). So the difference between undergrads and experts, although statistically significant, was hardly overwhelming.

Fifth, even the slightest use of “wisdom of crowds” was enough to overwhelm the expert advantage. A group of five undergrads averaged together had average error 115, again compared to individual experts’ error of 169! Five undergrads averaged together (115) did about as well as five experts averaged together (114). Twenty undergrads averaged together (95) did about as well as twenty experts averaged together (99).

Sixth, having even a little knowledge of individuals’ forecasting ability screened off expert status. The researchers gave forecasters some experimental data about the effects of a one-cent incentive and a ten-cent incentive, and asked them to predict the scores after a four-cent incentive – a simple, mechanical problem that just requires common sense. Randos who can do well on this problem do just as well as experts on the experiment as a whole. Likewise, randos who are noticed to do well on the first half of the experiment will do just as well as experts on the second half too. In other words, we’re back to finding “superforecasters”, people who are just consistently good at this kind of thing.

None of this seems to be too confounded by effort. The researchers are able to measure how much time people take on the task, whether they read the instructions carefully, etc. There is some advantage to not rushing through the task, but after that it doesn’t seem to matter much. They also try offering some of the Mechanical Turkers lots of money for getting the answers right. That doesn’t seem to help much either.

The researchers ask the experts to predict the results of this experiment. They (incorrectly) predict that prestigious academics with full professorships and lots of citations will do better than mere PhD students. They (incorrectly) predict that psychologists will do better than non-psychologists. They (correctly) predict that professors and PhD students will do better than undergrads and randos.

II.

What do we make of this?

I would tentatively suggest it doesn’t look like experts’ expertise is helping them very much here. Part of this is that experts in three different fields did about equally well in predicting the experimental results. But this is only weak evidence; it could be that the necessary expertise is shared among those three fields, or that each field contains one helpful insight and someone who knew all three fields would do better than any of the single-field experts.

But more important, randos who are able to answer a very simple question, or who do well on other similar problems, do just as well as the experts. This suggests it’s possible to get expert-level performance just by being clever, without any particular expertise.

So is it just IQ? This is a tempting explanation. The US average IQ is 100. The undergrads in this experiment came from Berkeley, and Berkeley undergrads have an average SAT of 1375 = average IQ of 133 (this seems really high, but apparently matches estimates from The Bell Curve and the Brain Size blog; however, see Vaniver’s point here). That same Brain Size post proposes that the average professor has an IQ of 133, but I would expect psychology/economics professors to be higher, plus most of the people in this experiment were from really good schools. If we assume professors are 135-140, then this would neatly predict the differences seen from MTurkers to undergrads to professors.

But the MBA students really don’t fit into this model. The experiment gets them from the University of Chicago Booth School of Business, which is the top business school in the country and has an average GMAT score of 740. That corresponds to an IQ of almost 150, meaning this should be the highest-IQ sample in the study, yet the MBAs do worse than the undergrads. Unless I’m missing something, this is fatal to an IQ-based explanation.

I think that, as in Superforecasting, the best explanation is a separate “rationality” skill which is somewhat predicted by high IQ and scientific training, but not identical to either of them. Although some scientific fields can help you learn the basics of thinking clearly, it doesn’t matter what field you’re in or whether you’re in any field at all as long as you get there somehow.

I’m still confused by the MBA students, and expect to remain so. All MBA students were undergraduates once upon a time. Most of them probably took at least one economics class, which was where the researchers found and recruited their own undergraduates from. And most of them were probably top students from top institutions, given that they made it into the best business school in the US. So how come Berkeley undergraduates taking an econ class outperform people who used to be Berkeley undergraduates taking an econ class, but are now older and wiser and probably a little more selected? It might be that business school selects against the rationality skill, or it might be that business students learn some kind of anti-insight that systematically misleads them in these kinds of problems.

(note that the MBAs don’t put in less effort than the other groups; if anything, the reverse pattern is found).

III.

Does this relate to interesting real-world issues like people’s trouble predicting this election?

One important caveat: this is all atheoretical. As far as I know, there’s no theory of psychology or economics that should let people predict how the incentive experiment would go. So it’s asking experts to use their intuition, supposedly primed by their expertise, to predict something they have no direct knowledge about. If the experiment were, say, physicists being asked to predict the speed of a falling object, or biologists being asked to predict how quickly a gene with a selective advantage would reach fixation, then we’d be in a very different position.

Another important caveat: predictive tasks are different than interpretative tasks. Ability to predict how an experiment will go without having any data differs from ability to crunch data in a complicated field and conclude that eg saturated fat causes/doesn’t cause heart attacks. I worry that a study like this might be used to discredit eg nutritional experts, and to argue that they might not be any better at nutrition than smart laymen. Whether or not this is true, the study doesn’t support it.

So one way of looking at it might be that this is a critique not of expertise, but of “punditry”. Engineers are still great at building bridges, doctors are still great at curing cancer, physicists are still great at knowing physics – but if you ask someone to predict something vaguely related to their field that they haven’t specifically developed and tested a theory to cope with, they won’t perform too far above bright undergrads. I think this is an important distinction.

But let’s also not get too complacent. The experts in this study clearly thought they would do better than PhD students. They thought that their professorships and studies and citations would help them. They were wrong. The distinction between punditry and expertise is pretty fuzzy. Had this study come out differently, I could have argued for placing nice clear lab experiments about incentive schemes in the “theory-based and amenable to expertise” category. You can spin a lot of things either direction.

I guess really the only conclusion you can draw from all of this is not to put any important decisions in the hands of people from top business schools.

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nikolap
12 days ago
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1 public comment
dmierkin
13 days ago
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Yes! People should stop asking physicist about politics!

Roman Flügel: All the Right Noises

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Roman Flügel has released hundreds of tracks over the roughly quarter-century since he began putting out records, and in them he has explored many permutations of four-on-the-floor dance music: hard techno, acid trance, willfully lunkheaded electro-house, lyrical deep house. The Frankfurt native doesn't tend to stay in any one place for too long. On his 2014 album Happiness Is Happening he delved into glinting synth-pop and Krautrock's motorik chug; earlier this year, his Verschiebung EP explored polyrhythmic drum sounds as dry and scratchy as strep throat.

Even within the context of that panoply of styles, All the Right Noises stands out as something we haven't heard from him before. The moods and sounds may be recognizable from his recent work, much of which has tilted toward contemplative states; glinting synthesizer patches transmit a pensive air, and the analog drum machines maintain a kind of stone-faced calm. But this is the furthest that Flügel has strayed from the dancefloor, at least for such an extended stretch.

It isn't strictly an ambient album. “Warm and Dewy” plows ahead at a quick-stepping 130 beats per minute, battered by tablas and brandishing hi-hats that couldn't be sharper if they'd come straight from the J.A. Henckels factory. (This, too, is new territory for Flügel: The drums sound a lot like he's been listening to Shackleton’s classic Skull Disco fare, in fact). But four-on-the-floor beats are an exception rather than the norm, and even when they appear, they make a beeline away from the functionalist dictates of contemporary dance music. Following the gorgeous, clear-eyed ambient opener, “Fantasy,” “The Mighty Suns” drops us into a curious kind of middle ground: It's fast-paced, but it feels half-speed; the pulse nods to dub, yet the bright keys and faintly naïve melodies echo Kraftwerk. It sweeps you up in colliding waves of contrapuntal melodies, a sensation at once both relaxing and slightly unsettling: You're never quite sure in which direction it will move next.

Rhythmically, the album peaks early, just three tracks in, with the polyrhythmic lurch of “Dead Idols.” Triplets snap against 4/4 rhythms, and an off-kilter clunk pulls the groove into a strange, elliptical shape; the first dozen times you hear it, you can practically feel your brain straining to parse the timekeeping. Shackleton's influence is audible here, too, along with the doomy menace of an artist like Demdike Stare, with wraithlike voices ratcheting up the tension as minor-key bleeps sound an ominous alarm. The rest of the album tackles far more soothing sounds: “Nameless Lake” harnesses the chirps and chimes of Amber-period Autechre; the elegant, strutting “Dust” reimagines Jean-Michel Jarre as downbeat acid; and the melancholy “Planet Zorg” is sad-sack ambient house with a hint of shoegaze thrown into the mix, sparking memories of Superpitcher remixing M83.

But the most satisfying material here may be the simplest. “Believers” offers the merest hint of kalimba plucks spun through delay and the occasional piano chord. Very little happens, and captivatingly so. The same goes for the closing song, which at first listen might sound like a new age spa soundtrack, complete with electronic crickets deep in the mix. Listen closely, though, and you can hear Flügel's playful spirit at work in the song's richly expressive piano and restless synthesizer improvisations. He effortlessly squeezes so many ideas into its barely-there, four-minute frame, it's easy to wish he'd settle in and record an entire album of such quietly masterful pastoral mood-setting.



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nikolap
14 days ago
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Okkyung Lee / Christian Marclay: Amalgam

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Christian Marclay was one of turntablism’s earliest pioneers. Throughout the 1980s, the multimedia artist plundered the discographies of others: scratching and refracting one Hendrix jam into a fresh psychedelic swirl, or layering several pieces by Chopin or Louis Armstrong into new soundscapes. Less indebted to hip-hop sonics than to the genre-blending aesthetics of John Zorn, Marclay eventually began to collaborate with a range of players that included Thurston Moore and Ikue Mori

Since his 24-hour installation film The Clock became a smash hit in contemporary art circles, Marclay has noticeably scaled back his turntablist practice. In recent years, he’s collaborated more with musicians through the interface of his collage-style “graphic scores.” But he still occasionally busts out his cartons of vinyl, as he did with the cellist Okkyung Lee for a 2014 performance at London’s Cafe Oto. Now released under the title Amalgam, the concert is easily one of Marclay’s most invigorating performances as a turntablist this century—and leagues more interesting than a pair of gigs released on limited-edition vinyl in conjunction with a 2015 gallery show in London.

A good deal of Amalgam’s success has to do with Marclay’s duet partner, Okkyung Lee. The cellist has demonstrated her avant-improv bona fides on her collaboration with piano great Cecil Taylor. And her own compositions display Lee’s skills with lyricism and melody, in between passages of crunch and noise. Appropriately, she has as many ideas for coaxing sounds from the cello as Marclay has strategies for abusing vinyl. This mutual acuity gives solid shape to their 36-minute, fully improvised performance.

After Marclay opens with samples that employ shifts in playback speed, Lee’s cello can be heard quietly, insistently repeating a short jagged phrase—a cellist’s imitation of a turntable scratch. Lee’s development of this brief figure gradually incorporates longer-held tones and broader fingerboard swoops, both of which help a listener identify her cello as the source of these particular sounds. By then, Marclay has begun splicing together noisier shards.

Not long after these discrete positions have been staked out by the two players, they pivot to blend their approaches. Occasionally, a figure that could have been produced by the live string player is revealed to be a Marclay sample, plucked from some string-laden LP. Metallic scrapings or atmospheric trails of sound production can seem like fodder from a vintage recording—until an expressive, violent burst in the line shows that this has all come from Lee’s cello.

This back and forth journey, between easy recognition of the different players and more ambiguous duo textures, creates much of the performance’s excitement at a minute-by-minute level. The larger structure follows a loose, three-movement style, with a quieter middle section that takes over in the fourteenth minute. Unlike many of Marclay’s past duo recordings with other artists, this session with Lee doesn’t include many recognizable samples. (You don’t even get any Anthony Braxton breaks that have cropped up in the turntablist’s collaborations with Elliott Sharp or Günter Müller.) But after this inspired performance, what lingers is the dazzling newness that Lee and Marclay create by exploring the outer fringes of timbre.



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nikolap
15 days ago
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Zagreb, Croatia
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Porter Ricks: Shadow Boat EP

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Porter Ricks, the duo of Andy Mellwig and Thomas Könerweren’t around for long, but they left an indelible stamp on the legacy of what came to be known as dub techno. Ironically, there was never very much dub in their work—not in the way that you could hear it ricocheting through the work of their colleagues Basic Channel, for instance, upon whose Chain Reaction label Porter Ricks released their debut album, in 1996. In Basic Channel’s music, dub is a root, transplanted from Jamaica, that will eventually branch into the full-scale reggae of their later Rhythm & Sound project. In Porter Ricks’ music, dub is less a root than a route, a way of tracing the path a sound can travel through the convoluted guts of the recording studio.

In Porter Ricks’ short, largely bulletproof catalog—save for a few exploratory detours on their second album, into hip-hop and Chicago house, that probably would have been better left untaken—drum machines are run through maze-like circuits until nothing remains but the infrared signature they have left in their wake. Their commitment to conjuring whole worlds out of little more than crackle and echo cast a long shadow, even though they put the project on hold after three short years. Without Porter Ricks, it’s hard to imagine Pole, Shackleton, Burial, or any number of artists working in the most densely crosshatched corners of electronic music. Their last album was 1999’s Symbiotics, a split LP with Techno Animal (the industrial duo of Kevin Martin, later known as the Bug, and Justin K. Broadrick, a veteran of a host of bands like Napalm Death, Godflesh, and Ice) on which their gravelly sound came to resemble something alive and malevolent, their synths’ jagged waveforms glinting like the teeth of a snarling animal.

On their first new work in 17 years, not much has outwardly changed—and really, that’s the best possible scenario. When they called it quits, they were still in the process of pushing their sound forward, so for them to pick up where they left off is a welcome development. Shadow Boat consists of just three tracks, but they cover a considerable amount of ground. “Harbour Chart” creeps ahead at 60 beats per minute, faint kick and hi-hat all but subsumed in a maelstrom of foghorns and static. “Bay Rouge” is faster, a brisk andante of glancing chords and metallic textures. The timing of the release couldn't be more perfect, given the way the track's movements mimic kicking up piles of dry autumn leaves; the whole thing is crisp, chilly, and brooding. “Shadow Boat” is the longest, quickest, and most intense of the bunch, a headlong tumble into a wind-tunnel rave, its synths rattling like a broken screen.

Porter Ricks always excelled at sketching out sweeping, subaquatic expanses—ironically, their name comes from a character on the 1960s television series Flipper, a children’s show about a dolphin, even though there’s nothing cuddly about their music—and that continues to be the case here; the sense of space suggested by all three tracks is immense, practically unbounded. For years, most dub techno records have concerned themselves with nothing more than dub techno itself, but Shadow Boat tackles bigger ideas: Its main subject is the interplay of uncontrollable forces. All three tracks, balancing four-to-the-floor beats with unpredictable explosions of sandblasted tone, explore the tension between steadiness and turmoil. On the one hand, the certainty of timekeeping; on the other, things ripped loose from their fixtures. (“Shadow Boat” would have made a great soundtrack to Alfonso Cuarón’s Gravity, playing the regularity of the spacecraft’s orbit against its spectacularly violent pulverization.) Ultimately, it’s not about chaos, exactly, but something like it: unpredictable, dubwise chain reactions that leave us cowed and awestruck—patterns whose complexity we can scarcely begin to apprehend.



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nikolap
15 days ago
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