Problems with Schizophrenia Comic

See this comic.

What’s the problem? The claim that the schizophrenic aren’t more dangerous. Actually, people with delusions are significantly more likely than those without to engage in physical assault – and the problem is that it’s very difficult to predict when they’ll do so.

Obviously, given ’sane’ individuals can be very violent too, and if a given schizophrenic has no history of violent reactions there’s really no reason to think they’ll suddenly start. But all else being equal, they’re a greater danger to others than they’d otherwise be.

I’m not even going to touch the discussion of what the causes of schizophrenia are – that topic requires more work than is suitable for this post.

Something to Keep in Mind

Remember: talking to yourself isn’t a sign of madness. Most of human “thought” is just self-referential monologue. The difference is that normal people repress the expression and don’t actually verbalize, while schizophrenics have something wrong with the internal censor that prevents the interior self-discussion from being spoken.

That scene in “Austin Powers: International Man of Mystery” where Austin’s interior monologue is spoken aloud as a consequence of cryogenic trauma? It was meant as an absurdity, but it’s more accurate than either the writers or the audience likely realized.

Thoughts on Charles Bonnet Syndrome

Possibly the most important lesson that should be taken from the story of Charles Bonnet Syndrome (CBS) is that correlation implies nothing about causation and even less about etiology.

Patients with general dementia, Alzheimer’s, or strokes were far more likely to communicate seeing things that weren’t there. So if you merely look at reported population statistics, visual hallucinations would seem to be associated very strongly with brain damage.

But the real problem was that such patients were much more likely to be uninhibited in talking about their hallucinations. Older people with loss of sight but properly-working minds feared the consequences of mentioning what they saw to anyone – at least partially because of the existing association in physicians’ minds between visual hallucinations and senility – and so said nothing. And so there was no awareness of the true rate of the phenomenon.

If you look at the actual statistics – the ones collected once the stigma of CBS was reduced, physician awareness increased, and elders gently but insistently questioned – then there’s no particular association between senility or brain disease and the hallucinations.

Remember – it took hundreds of years for the condition to even be mentioned in the English language, despite all of the people who must have experienced vision loss and CBS in that time. Despite all of the physicians who must have aged or had eye damage and suddenly experienced it themselves.

Morons on Neuroscience

See this comment over at Scalzi’s site.

This is why I love having a degree in Cognitive Psychology with an emphasis in neurology, because it lets me be fully justified when I point out the stupidity of statements like

There are judgements adults can make that children and even adolescents simply do not have the brain structures to make.

That’s utterly hilarious. The final stages of brain development, initiated at puberty, involve the destruction of connections and the massive pruning of redundancy. Adults have less potential and fewer brain structures than children and early adolescents, which is why they cannot pick up languages easily through casual experience, cannot learn to identify phonemes not present in their native languages, and have a very difficult time adopting or abolishing their existing accents and pronunciations.

There’s a tradeoff involved: greater speed and efficiency for impaired flexibility and potential. If you haven’t developed the capacity to do things once the pruning takes place, generally you never will. The late neural pruning exhibited by human beings is a major factor in our increased intelligence and flexibility compared to the majority of animals – the period in which they can learn and adapt is extremely limited, far more so than our own.

In adolescence, the brain changes from the child form to the adult form essentially from the back forwards: the old brain first, the new brain last. (Call that an example of ontogeny recapitulating phylogeny if you want.) Teenagers develop the ability to do crazy skateboard tricks YEARS before they develop the sense NOT to do them. The part of the brain that successfully predicts the consequences of actions develops only very late in adolescence, in fact one might say that the completion of that development IS the completion of adolescence.

Those ‘final stages of development’ involve the loss of the ability to develop functional systems, not their development. A person who hasn’t developed functional frontal structures by the time the pruning occurs will never do so. It in no way follows that the functional structures have not developed before the pruning – in fact, the existence of adults with effective frontal lobes is the definitive demonstration that such development occurs.

In terms of the legal definitions of child and adult, the distinction is arbitrary, having nothing to do with individual competence. There are lots and lots of adults that lack the competence it’s assumed they have because of their age, and lots and lots of legal minors who are far more competent than the adult average.

Hell, most adults never progress beyond concrete reasoning, even in advanced countries. It’s even worse in more primitive societies.

Cheryl Morgan on Gender

See her post on her website, Cheryl’s Mewsings, here.

It’s excellent except for this part:

However, there is a fair amount of evidence that some forms of gendered behavior have a biological component, and that treatment with hormones and similar chemicals, or even neuro-surgery, can cause animals to change their gendered behavior. Presumably the same is possible for humans.

The best available evidence is that it’s not. At least, not in any non-trivial sense – sufficiently advanced neurosurgery could change any behavior, and sufficiently primitive neurosurgery can eliminate any behavior. But that’s not what’s being discussed.

Identity and sexual orientation resist every mode of therapy and attempt to change known. It is possible to destroy cognitive function to the point where unusual concepts of identity and disapproved sexual orientations no longer manifest, certainly. But changing from one to the other? Can’t be done.

The article is definitely worth reading, and clarifies issues many people are confused about to a high degree. With such contentious issues of definition, I’m sure not everyone will agree completely with her usages, but they’re a good starting point for discussion.

[Edit: Clarification] The best available evidence is that orientation and gender identity cannot be changed in humans. I wasn’t trying to suggest that the evidence is against biological components to both those things – quite the opposite.

Principled Stands

Carl Zimmer has said that he will not participate in any further Blogginghead.tv discussions. So has Sean Carroll.

Good for them.

I should get around to adding them to my list of science-y blogs. I prefer to stay away from Discover, though, given my opinions on how they’ve changed over the past decade or so.

First, Do No Harm (Part 2)

What does Dr. Vertosick suggest is the cause of such snafus as the EC-IC bypass?

As the EC-IC bypass affair illustrates, experimental operations can jump into the medical mainstream long before anyone establishes their efficacy – or even their safety. Although ego and greed help keep unproved procedures in the operating room, it’s bad scientific judgment that puts them there in the first place.

Before new drugs can be marketed, they undergo three levels of testing. First, volunteers are given the drug to see how toxic it is and how well it’s absorbed and tolerated by the body. (This leads to specifically unexpected yet globally inevitable tragedies every once in a while, most particularly when one of the test subjects happens to be in a minority that has serious reactions to a drug that hadn’t been previously observed.) Then, once the obvious risks of the drug are known, it’s given to ill patients to see if they do better on it than previous, retrospective patients. Finally randomized trials are conducted to compare treated and untreated patients directly. Only when this last stage has been successfully completed is a drug considered for approval.

There is no such regulation on surgical procedures; although the FDA regulates surgical devices, it has no jurisdiction over surgeries. There is no legal obligation for surgeons to test therapies with the third stage of randomized trials. And since they can charge for any surgery, surgeons have no financial reason to put their therapies through expensive and difficult examination.

It is not unusual for surgical procedures to be widely implemented without rigorous testing – it is in fact quite standard. Vertosick offers the example of spinal fusion to treat back pain caused by degenerating disks. The disks can be removed “in a simple, two-hour operation”, or surgeons can remove the disk and implant a steel plate, which in theory helps to stabilize the spine, a procedure which is more involved and incidentally costs two to three times more. As Vertosick points out, “there’s no evidence that it’s any more effective than the simpler procedure”.

The reasons why so little testing is done are legion. It takes lots of money and effort to conduct randomized trials, patients don’t want to be assigned to “nonsurgical” groups – they want to be ‘treated’ when they go to surgeons, and that usually means undergoing surgery – and they go elsewhere for the surgery if they can’t get it in the study. Many doctors are not qualified to evaluate the statistical results produced, and often don’t believe the results when they arrive. Some of the critics of the NINCDS study initially complained that the best candidates for the surgery left and had the surgery elsewhere when they had been assigned to nontreatment, for example. But doctors often simply ignore studies, even when there aren’t potential confounding issues like that one, simply because they want to stick with what they “know” works.

What is known now is that the retrospective studies used by Yasargil did not accurately reflect the rates of stroke at that time. Too little was understood about how people’s health had changed between the time those studies were done and the time EC-IC was first being tested, and our assumptions that the two were comparable turned out to be wrong. As a result, Yasargil reached the wrong conclusion.

He didn’t even do something wrong – or at least, wronger than usual in medicine. He was in fact more careful than most such innovators, and certain more so than those who adopted his ideas without subjecting them to any testing at all. He was merely tragically wrong.

Other, equally tragic mistakes happen not through bad luck, but through incompetence, willful ignorance, and arrogance.

First, Do No Harm (Part 1)

Many years ago, as I read through the July 1998 edition of Discover magazine, I came across a fascinating essay entitled “First, Do No Harm”, by Frank T. Vertosick, Jr. (I later learned he was the author of a number of excellent books, including
When Air Hits Your Brain and Why We Hurt: The Natural History of Pain.) When I started reading it, I was idly curious; when I finished it , I was determined to skeptically examine the way medical decisions were made.

Sadly, I can’t provide a link to the article – although much of the content of Discover is available in various indexing and archival services, that particular commentary isn’t for reasons of copyright. But if you have access to back issues of the magazine, I highly you recommend you take a look at that particular edition; the essay begins on page 106.

What was so powerful about the essay that I remember it vividly more than a decade after I read it? Let me show you the bolded quote prominently displayed on its first page:

In the 1970s neurosurgeons began performing an operation designed to save lives. It actually risked them. But no one bothered to determine that for 20 years.

The human scalp is extremely well-supplied with blood to help keep body temperature under control by radiating away excess heat. In terms of immediate physiological requirements, the scalp doesn’t need anywhere near the total amount of blood that flows through it. Additionally, the peripheral arteries of the face and scalp tend not to become restricted or clogged with fatty deposits, with the result that many older patients have excellent blood flow in all parts of their heads but their brains.

Doctors began to think that redirecting this excess blood supply might be a good way to mitigate the devastating effects of strokes. When the brain wasn’t getting the blood it needed, why not borrow from the scalp? So in 1967, Dr. Gazi Yasargil of Switzerland was the first to conduct an extracranial-intracranial (EC-IC) bypass in humans, threading scalp arteries through the skull and grafting them onto the surface of the brain. Between then and 1976, he offered the surgery to 84 patients with a history of stroke or transient ischemic attacks, temporary blockages of blood in the brain that often warn of later strokes. In that time, only three of the patients had further strokes; based on older studies of similar patients, Yasargil concluded that more than half of his patients would have had strokes if he had not performed the surgeries, and that the EC-IC bypass was a highly effective preventative treatment.

Other neurosurgeons hadn’t waited for even this preliminary study to be concluded before offering the bypass themselves, years before any long-term investigation was possible. Thousands of surgeries were performed before even Yasargil’s results were published. As Vertosick reports:

Microsurgical laboratories sprang up overnight to teach the fine skills required for joining spaghetti-size arteries with sutures invisible to the naked eye. Large hospitals and universities aggressively recruited experienced bypass surgeons. Technically elegant and very lucrative, the operation became the darling of the neurosurgical community.

But technically early studies like Yasargil’s were only suggestive, not definitive. There was no proof that the therapy worked as well as we thought it did – they compared patients treated with surgery in the present with untreated patients from the past. That introduces the potential for biasing the results. Direct evidence would require comparing treated and untreated patients from equivalent populations in the present, with the absence of treating serving as a control.

In 1977, the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) began a study designed to do exactly that. 71 participating neurosurgical centers randomly assigned high-risk patients to either EC-IC followed by aspirin or aspirin alone. Nearly 1,400 patients had been studied when the trial ended in 1985.

Dr. Vertosick attended the conference at which the results of the study were publically released. Instead of confirming what the physicians believed to be true, the results abolished it. The surgery didn’t reduce the risk of stroke no matter how the data was examined. In fact, when deaths and strokes resulting from the surgery were included, the surgically-treated groups had more strokes with greater mortality than the groups given aspirin alone, averaging 14% more.

In other words, the EC-IC bypass wasn’t just useless, it caused significantly more strokes and deaths than doing nothing.

Yasargil’s beautiful theory died that day, slain by ugly facts. The now-wasted hours I had spent bypassing rat arteries flashed before my eyes. At the conclusion of the Honolulu talk, one of my colleagues approached me, cupped a hand to his ear, and lamented, “Did you hear that noise? The doors to a hundred microsurgical laboratories just slammed shut. For good.” Bypass mavens fought hard to save their operation, but to no avail. After a brief and acrimonious debate over the validity of the NINCDS study, the bypass era finally ended. Insurance companies stopped paying for the operation, halting its use; many surgeons still believed in it, but not enough to do it for free.

Although a minuscule number of bypasses are still performed for two rare, life-threatening brain diseases, the operation no longer has any role in the wholesale prevention of stroke. It now lies buried in the cemetery of dead therapies alongside bloodletting, head irradiation for ringworm, and a host of other harmful “cures”. Yet for nearly two decades, the best brain surgeons on earth inflicted thousands of operations on unsuspecting patients in the mistaken belief that the procedure was helping them. In doing so, they caused more death and destruction than the disease itself.

How could they have been so wrong?

That’s what the next post will be about.

Evaluations Needed

Hey, folks, I could use your help.

I’ve been reading the works of Raoul A. Robinson lately, and his ideas intrigue me. I’ve already formed a variety of opinions of the claims he makes, but I want other judgments.

Take a look at this article discussing some of his ideas, then consider reading his books, which are available for free download. (They’re really quite short – don’t let the high page counts faze you, the PDF pages are tiny.)

Then, please tell me what you think about the validity of his claims, the strengths of his ideas, and their weaknesses.

(Michael Vassar is specifically excluded from this request.)

Thanks.

Treating the Weapon

The man known as Paracelsus (see also Wikipedia’s entry) was unpopular and vilified in his day. But roughly thirty years after his death, his beliefs were taken up by those who wished to overturn Galenic physics, and so he ended up becoming highly influential and seriously affecting the development of medicine.

Many of his ideas are now recognizable as being worthwhile, although many are absurd, obvious superstitions. It’s worth crediting Parcelsus for what he got right, given that he represented a serious break with the worst elements of medieval thought, but his views were far from a modern understanding.

One of his more peculiar ideas was that injuries caused by weapons were best treated by ministering to the weapon responsible – or, if that were unavailable, to a stick coated in the blood of the injured person. The weapon (or stick) was rubbed with various ointments, wrapped in clean linens, and put away in a warm, dry place. To keep the weapon from spoiling.

No, really.

What is extraordinary about this belief was how long it was adhered to. I recall reading about how advocates of this method kept pestering the rebels in the American Revolution to treat gunshot injuries this way – particularly how one man claimed he had done a careful comparison of standard treatments and Paracelsus’, and found that weapon treatment was superior.

Thing is, he was right. What he didn’t realize was that treating the weapon was absolutely useless. It had no effect. It did nothing – except displace the normal treatments. The standard responses to such injuries were actually worse than doing nothing.

This highlights the importance of always keeping a control group when evaluating a method of doing something. If you don’t know what doing nothing looks like, you can’t judge what effect doing anything else has – including whatever it is that you want to test.

There’s a saying that resulted from this:

Treat the wound, not the weapon.

there should be another:

Test your assumptions, not your hypotheses.

Testing your hypotheses is important, but it can’t be done until your basic assumptions are validated.