The Mystery of Trephination

Why did ancient peoples cut holes in their heads?

The Woman of Pritschoena died around 4,500 years ago in what's now Saxony-Anhalt, Germany. Her skeleton was discovered in 1913 by a local archaeologist. Thanks to being buried in a gravel pit, her remains are exceptionally well preserved.

The Woman's skull is a fine example of trephination - the practice of deliberately cutting holes in the skull. She was trephined not once but twice, as you can see in the images above taken from a paper just out. In both cases, the skull around the hole shows clear evidence of healing, which shows that the Woman must have survived the procedures.

Trephination is a historical mystery. Stone-age peoples around the world were fond of doing it - trephinations have been found on skulls from Europe, the Americas and Asia. The authors of this paper say that there are records of at least 800 trephined skulls.

In some parts of Europe, it seems that the survival rate for the operation was over 90%. It was a delicate procedure, with stone tools used to carefully scrape away and remove the bone without damaging the tissue underneath. But no-one knows why they did it. Some argue that it may have been used as a treatment for epilepsy or mental illness, but it's impossible to really know what it was meant to achieve.

Alfieri, A., Strauss, C., Meller, H., Stoll-Tucker, B., Tacik, P., and Brandt, S. (2012). The Woman of Pritschoena: An Example of the German Neolithic Neurosurgery in Saxony-Anhalt Journal of the History of the Neurosciences, 21 (2), 139-146 DOI: 10.1080/0964704X.2011.575117

The Age of ADHD

Diagnosed rates of ADHD in American children have skyrocketed in the past 20 years, and use of medication such as Ritalin and Adderall has increased by an even greater amount.

So says a report just out in Clinical Pediatrics, using data from the major US National Ambulatory Medical Care Survey (NAMCS). The rate of office based visits (i.e. visits when a doctor saw or treated a patient, outside of a hospital) was the main outcome measure. The authors looked at the number of visits reporting a diagnosis of ADHD, and also the number of ADHD visits also involving psychostimulant medication, for kids aged 5 to 18.

See above - that's a big increase, and a lot of visits (remember the Y axis is visits per 1000 children per year.) One thing to remember is that the increase might not mean that there are more patients with ADHD -  it could reflect more visits per patient, but that seems unlikely to account for all of it.

A few thoughts -

The rise of ADHD parallels the recent increase in autism diagnoses. Yet people don't seem to be talking about it to the same extent. We're always hearing about "the autism epidemic", the "Age of Autism". Why aren't we equally concerned about the ADHD 'epidemic'? Why don't we have minor celebs railing about vaccine-damaged ADHD children?

Next - like autism - it seems likely that much or all of the increase is due to changes in awareness and willingness to diagnose the disorder. If so, logically, ADHD must either be being seriously overdiagnosed now, or was being seriously underdiagnosed previously. Or both.

This is especially true of boys. Rates in girls rose pretty much steadily for 15 years but in boys, there have been swings up and down, although the overall trend is still upward. It's always possible that this is a quirk of the NAMCS dataset, but if not, it suggests that ADHD diagnosis in boys is especially prone to changes in diagnostic fashion.

It's tempting, actually, to see the recent fall in boys with ADHD as a consequence of the rise of autism diagnoses over the same period. Autism is predominantly diagnosed in boys and the two disorders are often comorbid.

Maybe, boys are now getting autism diagnoses which are then felt to explain their behaviour, meaning that they don't "need" an ADHD diagnosis, which previously they would have got. But that's just my speculation, and it's probably reading too much into the data, because there was also a peak in 1994 which I can't see any explanation for.

Sclar DA, Robison LM, Bowen KA, Schmidt JM, Castillo LV, and Oganov AM (2012). Attention-Deficit/Hyperactivity Disorder Among Children and Adolescents in the United States: Trend in Diagnosis and Use of Pharmacotherapy by Gender. Clinical pediatrics PMID: 22399571

Fame Friday - Making its Return on BrandFabulousness

"It is up to us to live up to the legacy that was left for us, and to leave a legacy that is worthy of our children and of future generations." -Christine Gregoire

Beware Reverse Publication Bias

In all the fuss over the pressure for scientists to publish positive results, we may have been missing an equally dangerous kind of publication bias operating in the opposite direction.

So say Luijendijk and Koolman in the Journal of Clinical Epidemiology: The incentive to publish negative studies: how beta-blockers and depression got stuck in the publication cycle.

The background here is the possible link between beta blockers and depression. Beta blockers are drugs widely used to treat high blood pressure. Some studies have reported that they raise the risk of depression, though many others found no link. Propranolol is said by some to be the worst offender because it's best at entering the brain.

Luijendijk and Koolman say that beta blocker-depression studies have appeared in the form of "publication cycles" - first a positive study appears, and then negative ones follow. Then another study finds a positive link using a different method - and rebuttals, using those methods, soon appear. They sketch out several such positive-negative cycles based on different methods and particular hypotheses.

Now, there's two ways to look at this. You could explain this in terms of standard positive publication bias. Maybe lots of people looked into a possible link, the ones who found nothing didn't publish. Then someone, by chance, did find an association with depression, and they published it. Once that happens, the question became a hot topic so the unpublished negative studies were dusted off and submitted.

But there's a more worrying possibility. What if the original positive studies were correct, and the subsequent negative studies were the product of an inverse publication bias in favor of contrarian negative results?

The publication cycles in the literature about beta-blockers and depression seem to suggest that
the very publication of positive studies, whether true or false, increases the incentive to publish negative results, whether true or false... [in the case in question] the first as well as a significant number of subsequent negative studies were published in high-impact journals (8 of 19 journals with 2009 impact factor greater than 4.0). Third, power analysis showed thatd in two cycles, the first negative studies were underpowered...

If a true-positive study stimulated the publication of one or more false-negative studies, again an invalid picture of the true association would emerge. Publication of false-negative studies may thus give rise to publication bias, just like publication of false-positive studies. Research groups usually compete to get the first positive study published in a high-impact journal. It has been suggested that it could also be worthwhile to aim at getting the first study that challenges the former published.

This is not an entirely new idea. It was described in the classic Why Most Published Research Findings Are False, but only in passing.

To be honest it's impossible to know, in any particular case, whether inverse publication bias is at work. Depending upon whether you think beta blockers cause depression (and that's still controversial), your interpretation of the biases in the literature will probably differ.

However, I think the basic idea is important. Publication bias isn't a bias in favor of positive results per se. It's a bias towards "interesting" results - which in most cases means positive ones, but could equally well include negative ones, in certain contexts. In some ways, this could be a good thing, if the negative and positive biases eventually cancelled out, leaving a neutral playing field; but there's no guarantee that would ever happen.

As for how to fix publication bias - my opinions on that question are well known...

Luijendijk, H., and Koolman, X. (2012). The incentive to publish negative studies: how beta-blockers and depression got stuck in the publication cycle Journal of Clinical Epidemiology DOI: 10.1016/j.jclinepi.2011.06.022

The Unconquered World

A thought struck me the other day: China is the only place in the world that has never been controlled by a European power, whether as a colony, protectorate, territory, mandate, etc.

Thinking about it a bit more I realized this is not quite true, but it's not far off. As far as I can tell (thanks Wikipedia) the following countries were never officially under European control. I'm including the USA, Australia, New Zealand and the USSR as "European". Note that I use the modern names of countries to refer to the territory that falls within their borders, even though it wasn't always called that.

Most of China
Thailand
Mongolia
Saudi Arabia (assuming the Ottoman Empire was not a "European power")
Bhutan
Nepal

Iran and Turkey make the list, unless you count Alexander the Great.

Japan and North and South Korea make the list unless you count the post-WW2 occupations.

All of these areas were under various forms of influence at different times, but they never formally lost their sovereignty to Europe. (Edit: Iran and Turkey removed because they were conquered by Alexander.) (Edit 2: Added Bhutan and Nepal which I missed before. Changed map to show special status of Japan, Korea, Turkey & Iran).

Disclaimer: I'm not a geographer; this is something I put together purely out of interest. It's quite likely that I've missed some. In particular I don't know anything about the small island nations. Please comment if you can correct this, it's a work in progress.

Prop 8 Ruled Unconstitutional (Again)

Read the full decision here:
Ninth Circuit Prop. 8 decision

The Age (Cohort) of Autism

New data shed light on the recent mysterious rise in the number of kids being diagnosed with autism.

The new research doesn't explain the increase, but it tells us more about it. It shows that the rise in Californian autism diagnoses (reported to the state DDS) over the period 1996 to 2005 was a cohort effect, meaning that the rates of diagnosis have got higher, the later a child was born.

A child who's 10 today (born 2002) has double of the chance of having a recorded diagnosis compared to a 14-year-old born just four years earlier, in 1998.

"That doesn't tell us anything new!" you might object (I did at first). "All that means is that rates have risen, and we knew that already". But actually it does tell us something important. Because the data could have turned out differently; rates could have risen without a cohort effect, if, in recent years, lots of diagnoses were being handed to children regardless of their age.

That didn't happen. Almost all children in California who get a diagnosis, get it at age 3 or 4. In more recent years, the average age at diagnosis actually fell slightly. The peak used to be age 4, it's now 3.

So it's not that children in general have been getting diagnosed with autism more. It's that young children are getting diagnosed more; children aren't being diagnosed "retrospectively", as it were.

Another interesting finding is that the rise in rates of 'high-functioning' autism has been much bigger than the rise in low-functioning autism (i.e. autism alongside intellectual disability), although that has risen as well. Edit: but note that their defintion of 'functioning' is rather unique; see the comments.

So what does this mean?

These data are consistent with various interpretations. It could be that rates of autism have really risen in California over this time period. But it could also be that people are getting more likely to detect and diagnose it - in young children.

Keyes, K., Susser, E., Cheslack-Postava, K., Fountain, C., Liu, K., and Bearman, P. (2011). Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California International Journal of Epidemiology DOI: 10.1093/ije/dyr193

Fortune Best Companies List Hits LGBT Milestone

For the first time in history, all companies on Fortune's best 100 companies to work for list have sexual orientation nondiscrimination policies. Google tops the list. 

The Plight of Psychoanalysis?

A New York psychoanalyst reveals her concerns about the profession in A Letter to Freud: On the Plight of Psychoanalysis

Dinah M. Mendes's letter covers several topics, but I was struck by the sections that deal with the contemporary challenges facing American analysts. She paints a rather sad picture of analysts who spend years in training, only to find a shortage of people out there who want their treatment:

At psychoanalytic training institutes it is often difficult for candidates to secure control or training cases—prospective analysands who sign on with analysts-in-training, usually at a low rate (sometimes as low as $10 a session). Here the issue is not the cost of the analysis but the low valuation of the opportunity offered—what might be regarded as the gift of self-knowledge.

The gratifications of instantaneous communication—texting, Facebook, and blogging—are immediate and obvious and erode the value of the slow and arduous route to communication and understanding offered by psychoanalysis. We seem to be transfixed in our culture by the allure of performance and public presentation, and a climate in which the exterior signifies the interior, where what you see and hear is what is true and real (no matter how often this fantasy is belied) is not receptive to the ideals of psychoanalysis.

She goes on to examine the increasing popularity of psychodynamic psychotherapy, approaches which draws on Freud's ideas but is much shorter (and hence cheaper) than classical psychoanalysis which involves hourly sessions, three times per week, over a period of years -

To judge from the mushrooming of new institutes of psychotherapy and shorter training programs within established psychoanalytic institutes, many people are interested in becoming psychotherapists, while there are fewer candidates for traditional psychoanalytic training and for psychoanalysis as a treatment choice.

For those who elect full-scale psychoanalytic training, the supply of certified psychoanalysts exceeds the demand in the population, and as psychotherapists they compete with psychotherapists of all stripes and denominations. The analytic institute can feel like a sequestered haven in which psychoanalysis is an “in house” specialty, tendered by training analysts (who have to earn their institutional stripes) to analytic candidates...

In my years of training, the contemporary challenges facing the would-be practitioner of psychoanalysis were rarely if ever openly addressed, although many recent graduates find themselves with few and sometimes no analytic cases...

All this, she says, can be seen in the context of

A zeitgeist in which the intrinsic and often intangible value of knowledge and education, and of self-knowledge and self-examination, has been supplanted by the appeal of material and pragmatic goals.

Of course this is all anecdotal. I wonder if any analysts amongst my readers have thoughts on this?

Mendes, D. (2011). Letter to Freud: On the Plight of Psychoanalysis The Psychoanalytic Review, 98 (6), 755-774 DOI: 10.1521/prev.2011.98.6.755

Young, Canadian and on Antipsychotics

Antipsychotic use in Canadian children and teens is rising dramatically - prescriptions more than doubled in just 4 years, from 2005 to 2009.

That's according to a paper just out from Pringsheim et al. It's been known for a while that broadly the same is true of the USA. The data reveal that the Canadian border is no barrier to the spread of antipsychotics.

What's surprising is that while in the USA, some of these drugs are officially licensed for use in certain children and adolescent psychiatric disorders, in Canada all such use is off-label. That didn't stop there being nearly 700,000 youth prescriptions for an antipsychotic in 2009, in a country with a total population of 35 million - although bear in mind that this includes multiple prescriptions for the same person.

The growth in antipsychotics is accounted for by the second-generation "atypical" antipsychotics. Risperidone (Risperdal) was the biggest success story accounting for well over half of the total.


What's disturbing about this, as I've said before, is not so much the fact that these drugs are being used but the speed of the growth. It represents a fundamental shift in the way children and adolescent mental health problems are treated, one which has happened so fast that it's hard to believe that there was time to properly think through the consequences...

Use of SSRI antidepressants and psychostimulants (mainly ADHD drug methylphenidate, Ritalin) also rose between 05 and 09, but only by about 40%. That means that there were more antipsychotic than SSRI prescriptions in children and teens by 09, which is pretty remarkable.

Only 13% of the youth antipsychotic recommendations were actually for psychosis, the original indication of the drugs. The leading diagnosis was ADHD, which is odd, because the main drugs for ADHD, such as Ritalin, boost dopamine release, while antipsychotics block dopamine's effects via D2 receptors.


Other popular indications were mood disorders and conduct disorders. Overall, the fact that the vast majority of the antipsychotic prescriptions were not for psychosis confirms the view that the term "antipsychotic" for these drugs is misleading.

Pringsheim T, Lam D, and Patten SB (2011). The Pharmacoepidemiology of Antipsychotic Medications for Canadian Children and Adolescents: 2005-2009. Journal of child and adolescent psychopharmacology PMID: 22136092

"Mad Honey" Sex Is A Bad Idea

A cautionary tale from Turkey - do not eat poison honey to try to spice up your sex life.

"Mad honey" is honey made by bees from the nectar of toxic Rhododendron flowers. In places where wild Rhododendrons grow, including Turkey, it's a health hazard. The dangers of mad honey were known to the ancient Greeks and Romans, and it's reported that leaving tainted honeycombs in the path of invading armies was a popular military tactic.

2000 years later, some people still haven't quite got the message. According to a case report from cardiologists Yarlioglues et al, a married couple deliberately ate some mad honey "for reasons of sexual performance".

After eating one teaspoon per day for a week, they decided to crank it up a notch and ate a full tablespoon of the stuff. But their attempt to heighten their Turkish delight quickly turned sour, as they both suffered symptoms of confusion, chest pain, low blood pressure and slowed heartbeat. After presenting themselves to hospital, doctors discovered that they had both suffered an acute inferior myocardial infarction - a mild heart attack.

It's not clear whether the sex was a contributing factor.

The randy Rhododendron fans were lucky - following treatment, they both recovered. In fact, the authors say "To our knowledge, no fatal cases of mad-honey poisoning have been reported since ancient Roman times." However, it seems that some people are still willing to try their luck.

The toxin in mad honey is gryanotoxin. It acts by potentiating the opening of sodium channels, which are found both in the heart and the brain. This may be why it produces a combination of cardiovascular and psychoactive effects.

Mikail Yarlioglues et al (2011). Mad-Honey Sexual Activity and Acute Inferior Myocardial Infarctions in a Married Couple Texas Heart Institute Journal

Beware Good Theories

The ancient Greeks had a lovely theory. Certain places on the earth (caves, mostly) were, they thought, gateways to the underworld. Plants growing near these places could absorb the deadly essence of Hades and became poisonous.

Snakes and other venemous creatures got their poison by consuming these plants. And stinging insects got their little doses of poison by feeding off dead snakes.

Isn't that a great narrative? It explains everything, in a nice logical progression. OK, it presupposes what we would call a "supernatural" force as the ultimate origin of poison, but other than that, it's an entirely "scientific" account. In accordance with Occam's Razor, it proposes a single unified process underlying diverse phenomena.

It is, in other words, a perfect scientific theory. It's completely wrong, on every point, but we only know that because we now understand atoms, molecules, chemistry and biochemistry, which the Greeks had no way of knowing. At the time, the Hades theory was surely the best possible theory about where poison came from.

The moral of this story is, beware nice theories based on incomplete data.


Reference: Greek Fire, Poison Arrows and Scorpion Bombs, which I'm currently reading, all about chemical and biological weapons.

A Dangerous Truth about Antidepressants

An opinion piece by veteran psychiatrist and antidepressant drug researcher Sheldon Preskorn contains a remarkable historical note -

“A dangerous idea!” That was the response after a presentation I gave to a small group of academic leaders with an interest in psychopharmacology [over 15 years ago].

What evoked such a response? The acknowledgment that most currently available antidepressants specifically treat only one out of four patients with major depression based on the bulk of clinical trials data.

There was no argument about the accuracy of this statement, but...some claim it is “dangerous” to admit that the specific response rate to most antidepressants is 20%–30% because such an acknowledgment might undermine the value of antidepressant treatment.

By the "specific" response rate Preskorn means the number of depressed people who'll get better on antidepressants and who wouldn't have done so well on placebo. This rate is fairly low because, while most people get better on antidepressants, most of those improve on placebo as well.

Preskorn rejects the view that it's dangerous to acknowledge this:

...there are several problems with this reaction. First, it is hard to deny reality. The “placebo” response rate in antidepressant trials is arguably the most reproducible finding in psychiatry. Moreover, if available antidepressants were magic bullets, then polypharmacy would not be so common. Second, this reaction ignores the fact that antidepressants are tremendously valuable to the patients who specifically benefit from them...

Every treatment in every area of medicine has limitations. Acknowledging that fact should galvanize us to action. Denial on the other hand perpetuates the status quo.

Unfortunately, we're not told who these academic leaders were. I wonder if they included amongst their ranks some of the "key opinion leaders" in the field whose leadership proved rather less than ideal. The column is actually adapted from a 1996 article by Preskorn.

Preskorn is right, of course, that denying the fact that antidepressants are only substantially better than placebo in a fraction of people who get diagnosed with "depression" is wrong, and also misses the point: because hundreds of millions of Americans have diagnosable depression (due to the loose definition of "depression"), even if they only helped 1% of them, they'd still help over a million people.

But he doesn't mention that this approach was ultimately self-defeating. As a result of the failure to acknowledge that antidepressants are only helpful in some cases of depression (namely "severe" depression), these drugs became very widely used and - oh dear - people started saying that the drugs are being overused, and don't work in most people who take them.

Whoever could have seen that coming.

This has "devalued" antidepressants - and psychiatry itself - more than anything else has.

Preskorn SH (2011). What Do the Terms "Drug-Specific Response/Remission Rate" and "Placebo" Really Mean? Journal of psychiatric practice, 17 (6), 420-424 PMID: 22108399

Was Evita Lobotomized?

Eva Peron, or Evita, is perhaps the most famous woman in Latin American history. As the wife of Argentinian leader Juan Peron she was immensely popular. But she died at the age of just 33 from cervical cancer, after a two year struggle with the disease.

A new paper makes the startling claim that Eva Peron may have received a prefrontal lobotomy in the months before her death. The lobotomy is best known as a treatment for mental disorders such as schizophrenia, but according to Nijensohn et al, Peron was given the operation as a kind of pain relief.

The claim was first made in 2005 by Dr George Udvarhelyi, who worked as a neurosurgeon in Argentina before moving to John Hopkins in Baltimore. After his retirement, Udvarhelyi told the Baltimore Sun that he'd performed the operation.

The authors of this paper checked out the claims against his unpublished memoirs. It turns out that they've just written Udvarhelyi's biography, and managed to slip in a plug for their book. Indeed, this paper could be seen as a plug. But anyway.

The early 1950s were the golden age of lobotomy and it does seem plausible that if she had one, it would have been kept secret. But it seems that the only direct evidence is Udvarhelyi's testimony. The authors point to various facts that could be seen as consistent with it, like this memoir by a close friend:

“The illness continued to advance. I visited her one afternoon andwas shown a notebook belonging to her brother Juancito. There was a drawing of Evita with her head criss-crossed by scissors. The sinister image suggested that she was either crazy or brain damaged. I found her very thin, quiet, and deeply introverted”

But to be honest this is pretty weak. The authors also admit that in interviews with scholarly experts on Peron's illness, they were all surprised by the idea.

They then point to postmortem X-rays of Peron's skull which were made public in 1955 to prove that her corpse hadn't been burned (long story). These, they suggest, show evidence of the kind of burr holes that were used to insert the lobotomy tools -

And they say that a photo of her shortly before her death shows an "indentation at the coronal level" -

Hmm. Not sure what to make of those. Ultimately though, the authors admit that the only way to know for sure would be to exhume Evita and study her skull, but this is unlikely to happen any time soon.

Nijensohn DE, Savastano LE, Kaplan AD, & Laws ER Jr (2011). New Evidence of Prefrontal Lobotomy in the Last Months of the Illness of Eva Perón. World neurosurgery PMID: 22079825

Today's LGBT History Month Icon: Pedro Zamora

Today's LGBT History Month Icon: Dan Savage

The Limits of (Neuro)science

Will science ever understand the brain?

To start off with, it must be admitted that science has done a pretty good job of explaining pretty much everything else in the universe, so just going on past experience, it probably will.

But some say that, sure, the scientific method is fine for things like chemistry, but not for others. The human brain (or some aspect of it: consciousness, the mind, love, belief, or whatever) is the most popular exception. Science just won't work on it, we're told. It's too complex.

Maybe, but I find this view rather blinkered. It relies on taking our current state of knowledge as an eternal truth.

To see humanity as a mystery surrounded by a world of unmysterious things is a very new idea. It would have seemed bizarre just 300 years ago. Back then, nature was pretty much inscrutable. At best human life was no more mysterious. In many ways, less so. There were no end of philosophical, psychological and religious theories, many of them so plausible that they're still around today.

The notion that humans are complex and hard, while nature is easy, is an illusion created (ironically) by the successes of reductionist science. Some of the biggest questions facing mankind for eons have answered so well, that we don't even see them as questions. Why do people get sick? Bacteria and viruses. Why does the sun shine? Nuclear fusion. Easy.

But only easy now. Think of the billions of people who lived and died before say 1800 - they saw the sun every day and they had no idea why it shone, and they knew no-one else did. You may not understand nuclear fusion, but you know that physicists do, you know it's no mystery. 300 years ago, it would have been very tempting to think that no-one would ever know, that the answers were known only by God.

So, to confidently claim that explaining the human mind will just be too hard is presumptuous. It may or may not be, I don't know. Historically, though, the theory that things are inexplicable has a bad track record.

Then there's the idea that humanity is not so much hard, as different. Philosophers have spent many pages coming up with new ways of phrasing that point. Nature is material, but we're spiritual. Nature is in-itself, but we're for-itself. And so on. If we can understand the mind at all, it certainly won't be through reductionistic, mechanistic, rationalist, objectivist (phew) science, they say.

Again, this seems perfectly plausible... to us, now. But people used to say the same thing about living things in general. That was vitalism, the idea that physics and chemistry were fine for inert matter, but anything alive was radically different.

At a certain point in history, when biology was almost completely seperate from (and primitive compared to) the other sciences, that seemed fine. But it turned out to be wrong. With the benefit of hindsight. Nowadays, no-one sees a radically difference between nature and bacteria, plants or animals... well, except humans.

Maybe the mind will never be understood within the framework of the rest of science. I don't know, but I don't think anyone else does right now, either.

Today's LGBT History Month Icon: Ryan Murphy

New Documentary on Maine's Marriage Equality Vote

This looks quite good...

Today's LGBT History Month Icon: Constance McMillen