Schizophrenia and autism: evolutionary disorders?

I was thinking this morning, as I often do, of brain and mind, evolution, schizophrenia, and autism (more autism related posts), particularly in the context of a recent post about the perplexing prevalence of schizophrenia and a model of autism genetics involving spontaneous mutation, female non-expression, and inheritance in the male.

The pieces of the puzzle seem to fit together. If I were to read the minds of the researchers in these domains, I suspect they're beginning to think of autism and schizophrenia as examples of an entirely new class of illness - "evolutionary disorders". These are a class of disorders that arise in an organ, in this case the brain, that is undergoing rapid evolutionary change with a high mutation rate and a lot of suboptimal experiments.

I used to think that human evolution more or less ended with the invention of fire, at least that's what I recall from my high school essays [1]. Now we know that the human brain and human gut (they're very closely related systems) have undergone major adaptive changes within the past 15,000 years. It's increasingly plausible, but I don't think it's been proven, that these are systems predisposed to high mutation rates [2].

Systems predisposed to high mutation rates are going to produce a lot of "suboptimal" results, and a few significant improvements. This is what may account for the perplexing prevalence of two syndromes, autism and schizophrenia, that share similar traits:

• no obvious adaptive advantages
• common
• ill-defined and probably multiple underlying pathophysiologies
• complex genetic variability -- many different identified mutations and a suspicion that the disorders may arise from interacting protein networks.
  

I wonder if, should we look for them, we would identify similar "evolutionary disorders" in other animals undergoing rapid adaptive changes in some phenotype. Maybe that would explain all those odd-colored squirrels we see ...

[1] I've been fascinated by human evolution forever. Even as a child I didn't care for the traditional eugenics that is increasingly commonplace today, so I then advocated the encouragement of inter-ethnic marriage to dilute "bad" genes -- until we could directly engineer germ cell lines. Hey, it was a long time ago ...

[2] I think the theory here is that mutation rates can be selected for, so when "rapid change" is advantageous there is selection for "genomic creativity" over "genomic conservation". I think that's the mechanism that's supposed to underlie "punctuated equilibrium", but I'm not a biologist. I just write to learn ...

Update 5/6/2010: Yes, they're evolutionary disorders. In 2010 the term "evolutionary disorder" has a lot of hits, but I may have been one of the first users of it in this context.

Sudden shafts of light: the journalist as honest cop

DeLong and Krugman have long shone a noble light on the discredited "he said", "she said" style of journalism. This style requires that journalist be a neutral observer, reporting only what they're told. At most a journalist can hint, usually "below the fold", that some statement is an outrageous untruth.

This might have been a reasonable approach to pre-Gingrichian politics, but Gingrich's brilliance was to realize that "neutral observer" journalism provides a large adaptive advantage to liars. Market selection worked its magic and we ended up with the GOP congress and the Bush administration.

"He said" "She said" is a practice that needs to end. Journalists need to point out lies.

That's why I burst into joyous laughter during my commute today. My "In Our Time" podcast was hung up on the minutiae of medieval philosophy; it was reminding me too much of my work. So I turned to the radio to catch Lindsey Graham, a GOP senator, comparing the US occupation of Iraq with US opposition to Nazi Germany. Senator Graham told us that in those days real Americans rolled up their sleeves, and didn't worry about budgets, cost accounting or any "surtax" to cover war costs.

Without any noticeable change in inflection, the journalist said something like 'Of course Americans did pay a war surtax during WW II' and turned to the next topic.

It was brilliantly devastating. Graham was exposed as either a fool or a liar, or, most likely, both.

Dare we hope this is an early sign of a new dawn? It is time to bury the neutral observer, we need an "honest cop" style of journalism.

When government works - the Twin Cities

It's hard to remember a time when government was good in America. Clinton, whatever his other foibles [1], was a very good president -- but he was saddled for much of his presidency with the Gingrich House. About ten years ago Minnesota had a good (republican!) governor with a decent legislature, but then we got Ventura [2] and Pawlenty, and, for much of that time, a miserable GOP dominated House.

Politics and government in America has been dysfunctional for a surprisingly long time. I've grown accustomed to it.

So it was a bit of a surprise to me today when I noted that we have good local government in both Saint Paul and Minneapolis. In the case of Saint Paul, we dumped a traitorous Bush flunky and brought in a surprise winner who's turned out to be a good mayor.

My enlightenment came when I read a whiny editorial in a community newspaper (The Villager). The details don't matter, the key is that the complaints were so petty. The government is good enough, and rational enough, that they're arguing about issues that reasonable, rational, people can disagree on.

The ice rinks are one example. Inflation (3.5%) and cuts in state funding (Pawlenty!) mean more property taxes and a need to cut budgets. At the same time, it's pretty obvious we're losing our winters in Saint Paul. Outdoor ice just isn't working. The mayor wants to shut about nine outdoor rinks (they're mostly puddles these winters) and open 3 refrigerated rinks. Rational objectors worry about loss of summer fields (refrigerated rinks are fixed structures) or feel we should shut the outdoor rinks but not buy the refrigerated rinks -- which would mean saying good-bye to hockey and skating for most kids. A minority of loons seem to think winter is going to return any day now, which would be nice but is rather unlikely.

There are other small examples. I complained to my city counselor about scary intersection and the city took a serious look at it -- they'll even try to fix a few things. I was worried about a change to a busy street that seemed to promise more traffic, but it's a traffic calming measure.

This is good politics. It can happen, even if it's only at the level of a city ...

[1] Anyone who has what it takes to become President in the modern era is going to be a bit twisted. Clinton was twisted and competent, Bush is twisted and incompetent.
[2] Ventura was actually an improvement on the legislature of his day; he vetoed a lot of bad stuff.

Update 10/4/07: There's a great comment on my post about the refrigerated rinks; the commenter tells us those rinks are pretty loud at night. That sounds like something worthy of discussion! Should the rinks have mandatory noise abatement measures? Do the coolers need to run at night (probably not)? What's the experience where they've been put in -- do the neighbors find them as bad as feared? All good discussions -- that's what politics should be about. I can't say if these were discussed in the city council or not, but they should have been.

The treadmill powered Harry Potter eBook - my greatest invention

My wife is a reasonably disciplined person, but she has a dark secret. She's a binge reader. Lately she's been hitting the Potter pretty hard. Happily she's on the last one, so we're hoping to get her back on the wagon.

Me? Don't believe those Pratchett rumors. Damn you Vinge for luring me to that cursed drink ...

Which brings me to my greatest invention. The Potter powered treadmill. Hook up an eBook to a treadmill, so that there's a relationship between miles walked and page turning ability. If you don't walk enough, you find you can't turn the page any more ...

It won't cure binge reading, but it will extend the reader's lifespan...

Update 10/9/07: Jeff Atwood's post on "The Hacker's Diet" references the "gamercize" which uses exercise measures to limit computer or console access.

Condé Nast and Spam: what's the deal here?

Condé Nast Publications publishes "Gourmet" magazine. Judging by the ads the readership is classically bourgeois. So why do they generate so much spam? It's amazing -- every email address I've ever had gets spam from Conde Nast, usually about "Gourmet". Unsubscribe attempts always fail.

It's easy to eliminate -- I just block "condenastpubs.com". Still, it's weird. I suspect a good portion of the middle class doesn't mind getting spam from Gourmet ...

Update 10/14/07: Judging from a helpful comment, this appears to be a business decision by Conde Nast, not a technical error or a fluke. I think there's a strong case to be made for blacklisting the condenast.com domain.

Incidentally, as of today a Google search on "conde nast spam" has this blog post as the top hit. I suspect someone from Conde Nast is going to read this. They can add their comments below, i promise I'll publish them. They can't email me, since I've blacklisted their domain.

Update 1/18/07: I got another Gourmet magazine spam -- but the domain was erol.com. Turns out this is not a Gourmet spam after all; it's a phishing email. I suspect even Conde Nast hasn't fallen that far. It's a measure of how low they have fallen, however, that phishers are now riding their spammy coattails.

Nokia is the Apple Geek's new best friend

Where can an Apple geek look for help, now that Apple is beating on its most loyal customers?

Into our hour of darkness and despair rides an unexpected savior - Nokia! (emphases mine):

AppleInsider | Nokia launches anti-iPhone campaign amid controversy

Bloggers and hackers aren't the only ones sticking it to iPhone maker Apple Inc. for its closed minded approach to user-customization of the touch-screen handsets -- Nokia has taken advantage of the situation by launching a print and web campaign dubbed "Open to anything."

"We believe the best devices have no limits. That's why we've left the Nokia Nseries open," the Finland-based handset maker wrote on its new "Open to anything" website. "Open to applications. Open to widgets. Open to anything. So go ahead and load it up. What is does is up to you."

The campaign, which was accompanied by the posting of similarly-worded bills in New York City this past weekend, is an obvious response to the latest iPhone update on Thursday...

...The matter is complicated by a number of factors, primarily what is now being perceived by some as a poor job on Apple's part to convey its stance on third-party applications to iPhone users earlier in the handset's lifecycle...

Ahh, balm to our wounds.

Nokia placed two full page ads in the paper NYT about 10 days ago beating up on Apple's control fetish. I didn't comment at the time because I couldn't find any related marketing material on Nokia's web site, but it seems their dysfunctional marketing department is catching up.

This has got to cause pain in Cupertino. Alas this is probably not a good strategic move for Nokia; it's just the sort of thing that might cause Apple (and AT&T?) to change direction. Nokia would be best served by Apple continuing on their current path of self-destruction...

I wonder if Nokia will support iSync?

PS. Nokia has a very annoying flash based web site. I didn't say the Nokia was a smart company ...

Dyer on why Bush invaded Iraq - not the oil

Dyer is no fan of George Bush's rule. In a recent essay, however, he disparages the common belief that Cheney/Bush invaded Iraq to protect the west's oil supply. So what was the reason?

... So why did they invade Iraq, in the end? One motive was certainly the desire for permanent American military bases in the Gulf from which the United States could, at need, stop oil flowing to China. The strategic community in Washington has identified China as America's new strategic rival, and it is becoming more and more vulnerable to interference with its oil imports. (Those 'enduring bases' are still being built in Iraq.) But that is not a big enough reason to explain what happened. I have written tens of thousands of words on the Bush administration's motives for invading Iraq, but in the end I do not know why they did it. I suspect that they don't, either. It just seemed like a neat idea at the time...

More Dyer essays: 8/20-9/17 2007

More Dyer essays:

Gwynne Dyer: 2007

August 20 British Retreat From Iraq
August 27 Sarkozy: The Hyper-President
August 30 Islam and the Idiotic Autocrats
Sept 4 Extreme Climate and Extreme Politics
Sept 6 Terrorism: Lessons from Germany
Sept 10 Marking Time
Sept 17 It's All About Oil

Is schizophrenia the price we pay for an evolving brain?

Schizophrenia is pretty darned common, and it's a terrible disorder with clear inherited roots. So why is it so common?

Scientific American 9/6/07: It's No Delusion: Evolution May Favor Schizophrenia Genes

New research reveals that genes related to the debilitating disorder may also provide developmental advantages..

...Dorus co-authored a report, appearing in this week's Proceedings of the Royal Society B, about the evolution of genes linked to schizophrenia. After analyzing human DNA from several populations around the world and examining primate genomes dating back to the shared ancestor of both humans and chimpanzees, researchers reached a striking conclusion that several gene variants linked to schizophrenia were actually positively selected and remained largely unchanged over time, suggesting that there was some advantage to having them.

"Schizophrenia can be explained by a lot of individual alleles (variations of genes)," Dorus notes. "There are many different loci that impact the actual manifestation of the disease." Over the past decade, several dozen genes have been identified as potential culprits, and scientists believe that several genes cause disruptions in protein formations predisposing a person to schizophrenia.

...the team ... focused on 76 gene variations most strongly related to schizophrenia. By comparing these combinations with the evolution of other genes known to affect neuronal processes, the researchers determined that 28 of the schizophrenia-associated genes have been evolutionarily preferred in recent years by either Caucasian, Asian or African populations.

"Because it's a such a complex genetic trait … you actually expect there to be some variability from population to population, in terms of what genes are playing a role in the disorder," Dorus says. He notes that he was surprised that the study turned up a positive selection for some of the genes most closely associated to the disease, including DISC1 (disrupted in schizophrenia 1), which is involved in the transport of proteins along the relatively lengthy cell bodies of neurons, among them. "The most important thing is we don't really know what the basis of the selection has been," he says. "It could be due to an entire range of neurodevelopmental processes."

Co-author Crespi says that a number of theories have been floating around regarding the persistence of schizophrenia's genetic underpinnings. One holds that schizophrenia is a "disorder of language" and that the illness is an unfortunate consequence of the development of human speech, expression and creativity. "Whenever you get strong selection, it's like a big plus, and you can drag along a lot of minuses," he says. "You can think of schizophrenics as paying the price of all the cognitive and language skills that humans have—they have too many of the alleles that taken individually…might have positive effect, but together they are bad."

Dorus says the team will now home in on the 28 genes fingered in positive selection in the hope of finding new treatments for the mysterious disorder.

The explanation seems to be that it's very hard to construct a functioning human brain, and that the brain is still actively evolving. So in this case there's not necessarily an advantage to a schizophrenia gene, but rather that the diffuse set of disorders we label as "schizophrenia" arise because the human brain is very much a work in progress, one with a high defect rate ...

Update 7/2/2010: Structural variation in the human genome and its r... [Annu Rev Med. 2010]...

... The discovery of submicroscopic copy-number variations (CNVs) present in our genomes has changed dramatically our perspective on DNA structural variation and disease. ... CNVs, to a larger extent than SNPs, have been shown to be responsible for human evolution, genetic diversity between individuals, and a rapidly increasing number of traits or susceptibility to traits; such conditions have been referred to as genomic disorders. In addition to well-known sporadic chromosomal microdeletion syndromes and Mendelian diseases, many common complex traits including autism and schizophrenia can result from CNVs. Both recombination- and replication-based mechanisms for CNV formation have been described.

A picture to remember - Rangoon

TIME, September 27, 2007

Pictures of the Week - TIME

Photographer Kenji Nagai takes photographs after being shot by soldiers in Rangoon as the Burmese Army fired on the crowd. Kenji later died.

Send a letter to Rush

Army of Dude: The Real Deal is a post from a former Limbaugh listener, and veteran, who's opinions have changed. Apparently the latest right wing meme is to label any veteran who disagrees with them a "phony soldier". I'm sure someone will send it to Rush as a letter ...

Apple guilty of second degree iPhone murder?

We know there's a civil war brewing between Apple and an arguably critical part of their customer base -- the OS X geek community. If it turns out that Apple deliberately configured the latest OS X update to destroy hacked iPhones, the conflict will move up a notch. Glenn Fleishman of the venerable and respected Tidbits organization says Apple is not guilty of iphoneslaughter, but rather of murder in the second degree ...

TidBITS iPod & iPhone: Staff Roundtable: Apple Should Do No Harm to iPhones

... Apple has changed that equation with the iPhone's latest firmware and operating system upgrade. The iPhone is a powerful little computer controlled by powerful interests. Like almost all electronics sold today, includes a variety of kinds of firmware, or the software that controls the hardware. The firmware may be stored in different places, too, with radio cards and separate modules have their own internal firmware. Part of the firmware handles the boot procedure that allows the device to load the operating system; other parts handle upgrading and installing new firmware. Because the iPhone uses non-volatile, electrically erasable memory, there should be no problem with restoring a phone that has had every manner of change applied to it, as long as the boot routines aren't affected.

The hacks that unlock an iPhone to work with other carriers write special instructions to the firmware that controls the cellular network association to allow the use of any SIM - the authentication module used on worldwide GSM cellular networks - and not just AT&T's. This shouldn't affect the bootstrapping or firmware and operating system restore process one bit.

Gizmodo posted an interview with the iPhone Dev Team, a community effort that resulted in unlocking software. In the interview, the Dev Team makes it clear that Apple could very simply have included in the update a way to check whether the code related to the lock has been modified, and rewrite it. The team says that Apple could also fairly easily restore a default state and then more securely lock the phone down. (The team is also positive they can restore iPhones to a factory default state that have been "bricked," or turned into an unusable hunk of electronics.)

Has Apple lost its collective mind?

Bicycling and Skating: Urban variations?

Minneapolis is a great bicycling city, and Saint Paul is not far behind. On the other hand, we don't have as many inline skaters as one might expect. We invented the darned sport (ignore the cheese heads in the corner please), but our Friday Night Skates occur only twice a month, and we rarely get more than twenty skaters. Our inline skate club is a great group, but we're a bit on the ... experienced side of 40 (I'm going to sign up my 10 yo to drop our average age).

So why do many of these cities have pretty active night skates, not to mention Amsterdam and especially Paris?

... It takes place every Friday night, except when it rains, and can attract as many as 20,000 skaters. Group skates have been around awhile in the United States and Europe, especially since the advent of in-line skates, which provide speed and maneuverability not possible with quad roller skates. But, in scale and longevity, nothing matches the festive Parisian skates, which began in a small way in 1994 and quickly grew to a point where, in 1997, the police decided to become involved for the safety of everyone concerned -- skaters, motorists, and onlookers. Today, the police not only block off roads and provide an escort for the skaters, but about 20 officers on skates join the rolling ranks during the weekly "rando," derived from the French word "randonée," or tour...

Ok, so Paris is bigger and has lots of tourists. Still, you think we'd be able to muster a few hundred!

One theory I've heard is that the bicycling and skating populations are very similar people. In Minneapolis that population bicycles, but in other cities the bicycle routes aren't nearly as appealing -- so skating is more common. Of course that doesn't explain Amsterdam ...

Curious. I do think we ought to try a weekly skate, but since I get free to join 'em only about twice a year I'll have to wait for someone else to make that happen.

Helmets: good for inline, not so good for bicycling?

Inline skaters should wear a helmet. But what about bicyclists? I wear a bike helmet, and so do my children. It seems to make sense anyone riding on a bicycle path, but today I read that it may not work for anyone riding with cars.

The problem, alas, is the car driver.

Cars are not much of a factor in head injuries occurring during inline skating; inline skaters rarely mingle with cars. Bicycles, however, do. Most bike fatalities and injuries are automobile related.

It turns out that automobile drivers, on average, give more space to bicyclists not wearing a helmet. If you wear a helmet, there's a 23% increase in automobiles passing within the 1 meter danger zone [1]

I suspect that this is doubly true for motorcyclists, though the researchers did not study that topic. So much for all my disparaging remarks about bare headed motorcyclists; if my guess is right than the decreased risk of automotive impact will far outweigh the decrease in head protection. Aging boomers -- let your residual hair flow free ...

Maybe.

So what do we do while researchers sort this out? If you're not riding in traffic the evidence strongly favors riding a bicycle helmet. If you ride in traffic, however, things are trickier than I'd once believed. There's a case for putting the helmet on the bike rack when entering traffic, and donning it for the bike trail...

I won't change what I do. For one thing surprising results require confirmation, for another I need to reinforce the children's behavior. For them the helmet is an unadulterated good.

In the meantime, let's find out what other things we can do to get more space from cars. How about a horizontal flag that extends one foot left? Professor Walker, please retest with the flag. Let's see what we can do to get those drivers outside the 3 foot limit. Maybe a flag and a helmet together will provide both head protection and a lower impact risk.

[1] Scientfic American Fact or Fiction, October 2007. Walker et al, Accident Analysis and Prevention, March 2007. The summary didn't mention gender variation. My experience is that women drivers give much less room than men drivers, perhaps because of a greater reluctance to cross the solid center line.

DI - Lake Peigneur

It's only 27 years ago, you'd think I'd remember this ...

Damn Interesting » Lake Peigneur: The Swirling Vortex of Doom

...Within two days, what had previously been an eleven-foot-deep freshwater body was replaced with a 1,300-foot-deep saltwater lake....

Turns out there's a good reason I don't remember this. The NYT story from 11/21/1980 is a brief, understated, summary within the "In the Nation" column.

There's a interesting gap between the miniscule national attention given the story in 1980 and what had really happened. Today it would be on FOX and CNN around the clock.