Effect of antidepressants exaggerated due to buried data

The New England Journal of Medicine has just published a study that found the effectiveness of 12 of the most popular antidepressants has been exaggerated because pharmaceutical companies have been ‘hiding’ data from negative drug trials.

Known as the ‘file drawer effect‘, it involves submitting only positive results to be published in scientific journals.

This type of selective publishing was recognised as a pervasive problem in medicine, and to try and combat this, a rule was introduced that required all clinical trials to be registered before they began.

This means no-one could claim that a negative study didn’t occur and others could try and track down the data if needed.

The researchers in this new study decide to do exactly this. They examined the American Food and Drug Admistration (FDA) register and requested data from all 74 trials of the most commonly used antidepressant drugs.

They then compared the results from all the trials, to just the trials that had been published in the medical literature.

The findings are quite shocking:

A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published.

Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies).

According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive.

In other words, when all the studies are examined, there’s only about 50-50 chance that a scientific study of an antidepressant drug will find it more effective than placebo in treating depression.

The Wall Street Journal has a good write-up of the study, from which I’ve also taken the graph below. It describes which antidepressant drugs have their apparent effect most boosted by the hiding of negative findings.

As we live in the age of ‘evidence based medicine’, doctors will used the available evidence to decide which drugs to prescribe.

Needless to say, distortions in the published results can affect individual patients owing to the effect on doctors decision-making.

Link to abstract of study.
Link to good write-up from the Wall Street Journal.

Can stress stop the menstrual cycle?

Inkling has an interesting article on the effect of stress on the menstrual cycle that investigates the received wisdom that stress can prevent periods.

It turns out the scientific studies have found no conclusive answer as they’ve returned mixed results, but this may be because they don’t adequately distinguish between physical stress and psychological stress.

A range of physical health problems are known to halt menstruation. Malnutrition is a common example and this is why women with anorexia often don’t have periods.

Of course, physical and psychological stress go hand in hand, but one study that looked at healthy young women under a great deal of psychological stress, but no major physical health problems, found no alteration in the menstrual cycle.

So Ellison examined female juniors at Harvard who were preparing for the MCAT [Medical College Admission Test] and compared their anxiety levels (and ovulation schedules) to women who were not preparing for the MCAT. In order to make sure there were no other factors at play, all the women were otherwise physically healthy, were not using any oral contraceptive pill that would change hormone levels, and all reported normal ovulation…

But despite the significant increase in stress, there was no change in ovulation or periods in either group. No matter how stressed these students were about the upcoming exam, they continued to have a visit from Aunt Flow right on schedule. This was even the case during the final days and weeks leading up to the MCAT exam, when the subjects described intense stress levels that only Harvard pre-meds can sustain. The study was published in the December 2007 issue of the American Journal of Physical Anthropology.

There’s more on the effects of stress on menstruation in the article.

Link to Inkling article ‘Of Stress and Periods’.

Artistic assault

This is a completely amazing case report published in Acta Neurochirurgica about a man who managed to get a paintbrush stuck in his brain during a fight.

The most astounding thing is that from the outside it only looked like he had a tiny cut on the eye.

Artistic assault: an unusual penetrating head injury reported as a trivial facial trauma.

Mandat TS, Honey CR, Peters DA, Sharma BR.

The authors report a case of penetrating head injury that presented with a deceptively mild complaint. To our knowledge, it is the first report of a paint brush penetrating the brain. The patient reported being punched in the left eye and presented with a minor headache, swelling around the left orbit, a small cut on the cheek and slightly reduced left eye abduction. After radiological evaluation, a penetrating head injury was diagnosed.

Under general anesthesia, through a lateral eyelid incision a 10.5 cm long paint brush, which had penetrated from the left orbit to the right thalamus, was removed. No post-operative infection was seen at six months follow-up. This brief report serves to highlight that penetrating brain injury can occur without neurological deficit and that a minimally invasive surgical approach was successful in avoiding any complications.

Link to Pubmed abstract.

Mind, body and goal: the embodied cognition revolution

The Boston Globe just published an excellent article on ‘embodied cognition‘, an area that’s recently been getting a lot of attention in cognitive science and which argues that we can’t understand psychology without understanding the body and our actions.

The reason it’s so potentially revolutionary is that it challenges the idea that psychology can be understood as a purely abstract mental process and suggests that our mind is shaped as much by our body and how we physically interact with the environment as by ‘passive’ sensory experience.

In other words, the reason we’ve developed thinking brains is to allow us to act, and so the possibilities, limitations and feedback from actions must shape our psychology – both in the long term as a species (via evolution) and in the short term as individuals (via learning and plasticity).

The body, it appears, can subtly shape people’s preferences. A study led by John Cacioppo, director of the Center for Cognitive and Social Neuroscience at the University of Chicago, found that subjects (all non-Chinese speakers) shown a series of Chinese ideographs while either pushing down or pulling up on a table in front of them will say they prefer the ideographs they saw when pulling upward over the ones they saw while pushing downward. Work by Beilock and Holt found that expert typists, when shown pairs of two-letter combinations and told to pick their favorite, tend to pick the pairs that are easier to type – without being able to explain why they did so.

Some of my favourite research in this area is by psychologist Dennis Proffitt who has found a range of bodily effects on perception.

In one particularly striking study, Proffitt and his colleagues found that we perceive distances as shorter when we have a tool in our hand, but only when we intend to use it.

They suggest that we perceive the environment in terms of our intentions and abilities to act within it.

Link to Boston Globe article ‘Don’t just stand there, think’.
Link to great introduction to embodied cognition.

Pirahã: the world’s most controversial language

It’s probably true to say that Pirahã is the most controversial language in the world owing to Daniel Everett arguing that the language doesn’t have recursion, as Chomsky’s ‘universal’ language theory predicts, and doesn’t have fixed words for numbers or colours.

New Scientist has just put a video online that is a superbrief introduction to Everett’s theory, but best of all, we get to hear the language spoken.

Everett is also interviewed in this week’s issue of the science magazine, but it’s behind a pay wall, so I’d just read it in the newsagent.

However, if you want more detail over the controversy, it’s been well covered in other places.

Edge had an article by Everett that put his case forward, NPR had a radio show on the debate, and The New Yorker has some wonderfully in-depth coverage of the issue.

Link to brief video of Everett at work.

Jesuit hypochondria in early modern Naples

I always assumed Early Science and Medicine was what happened during 9am ward meetings, but it’s apparently an academic history journal.

In a recent issue, it has a curious article that discusses a ‘plague’ of ‘hypochondria‘ (an unfounded fear of serious illness) that apparently swept through the Jesuit community in 17th century Naples.

The first sentence of the abstract is completely priceless.

Poetry or pathology? Jesuit hypochondria in early modern Naples.

Early Science and Medicine, 12 (2), 187-213.

Haskell Y.

In their didactic poems on fishing and chocolate, both published in 1689, two Neapolitan Jesuits digressed to record and lament a devastating ‘plague’ of ‘hypochondria’. The poetic plagues of Niccol√≤ Giannettasio and Tommaso Strozzi have literary precedents in Lucretius, Vergil, and Fracastoro, but it will be argued that they also have a real, contemporary significance. Hypochondria was considered to be a serious (and epidemic) illness in the seventeenth century, with symptoms ranging from depression to delusions. Not only did our Jesuit poets claim to have suffered from it, but so did prominent members of the ‘Accademia degl’Investiganti’, a scientific society in Naples that was at odds with both the religious and medical establishments.

Link to PubMed entry.

I take your brain to another dimension

Pay close attention. The New York Times has an article on the Boltzmann brain theory that argues that random fluctuations in the universe could create self-aware entities. In other words, brains, being spontaneously created by the universe.

It turns out, the theory isn’t solely about brains. It argues that matter could be created from fluctuations in the universe and it is mathematically conceivable that one of these fluctuations could create matter configured as a conscious creature.

Like Nick Bostrom’s ‘we could be living in a computer simulation’ argument, it takes mathematically possibilities to their most astonishing extreme.

Regardless of the infinitesimally small probability of this actually happening, it does lead to some wonderful language in the article.

Where else are you going to read the sentence: “The numbers of regular and freak observers are both infinite.”

Link to NYT article ‘Big Brain Theory: Have Cosmologists Lost Theirs?’

It’s not a symptom, it’s irony

The Utne Reader has a shocking article on a near medical tragedy – a misdiagnosis of depression that led to inappropriate medication and the patient almost being given electroshock treatment.

Luckily, one of the more cultural sensitive of the medical staff noticed the patient’s normal behaviour was being inappropriately pathologised as mental illness.

George Farthing, an expatriate British man living in America, was diagnosed as clinically depressed, tanked up on antidepressants, and scheduled for a controversial shock therapy when doctors realized he wasn’t depressed at all, he was just British!

Farthing, a man whose characteristic pessimism and gloomy perspective were interpreted as serious clinical depression, was led on a nightmare journey through the American psychiatric system. Doctors described Farthing as suffering from pervasive negative anticipation: a belief that everything will turn out for the worst, whether it’s trains arriving late, England’s chances of winning any national sports events, or his own prospects of getting ahead in life. The doctors reported that the satisfaction he seemed to get from his pessimism was particularly pathological.

You can read the full story at the link below for all the shocking details.

Of course, it would be churlish not to mention Whybrow and Gartner’s theory that the personality of the American people reflects the fact that they have a greater genetic propensity for mania.

Yes, they are being serious. You may wish to insert your own comment about the genetic propensity for irony at this point.

Link to article ‘Not Depressed, Just British!’ (via TWS).

The anatomy of fashion

T-shirt fashionistas Alphanumeric have created an anatomically labelled brain t-shirt, so you never have to decide between wearing a t-shirt or taking your neuroanatomy textbook with you.

Of course, if ever you were in a situation where you needed to choose between clothes or a neuroanatomy book, you might have more to worry about than the accurate labelling of brain parts.

Needless to say, while naked neuroanatomy might be the way forward, this t-shirt might suffice in the mean time.

Link to Alphanumeric brain t-shirt (via HYA).

Mapping emotions onto the city streets

Christian Nold maps cities. But instead of mapping their physical layout, he maps their emotional geography.

He uses a technique he invented called biomapping where participants walk the area connected to a system that measures galvanic skin response – a measure of the electrical resistance of the skin which is known to give a rating of arousal and stress.

The system is also connected to a GPS device, so the stress response of each person is physically mapped onto the landscape.

His maps describe an area in terms of how stressful it is, and so far, he’s mapped Greenwich in London, San Francisco and Stockport.

He’s also done a project that maps the sensory experiences of Newham.

I had the pleasure of meeting Christian the other night and one of the best things is is that he’s persuaded Ordinance Survey, the UK’s mapping agency, to print the maps!

I have a copy of the Greenwich map and so far everyone I’ve showed it to has been blown away.

You can buy paper copies of the maps, but also view them in full detail online.

Link to Emotion Map.
Link to Christian Nold’s website.

Higher price makes cheap wine taste better

A new brain scanning study has supported what we’ve suspected all along, more expensive wine tastes better partly because we expect it to.

Neuroscientist Hilke Plassman led a brain-scanning study [pdf], shortly to be published in the Proceedings of the National Academy of Sciences, where volunteers were asked to taste and rate five different wines, each individually priced.

What the volunteers didn’t know was that there were only three different wines, and two of them were tasted twice. One one occasion it was described as costing $90 a bottle, on another as costing $10 a bottle.

The volunteers rated the ‘more expensive’ wine as significantly more likeable despite being identical to the ‘cheaper’ wine.

In addition, the brain scans showed when the volunteers tasted the wine they thought was more expensive, their brains showed increased activity in the medial orbitofrontal cortex (mOFC) and its surrounding area, the rostral anterior cingulate cortex (rACC), both areas of the frontal lobes.

The orbitofrontal cortex is known to be involved in the regulation of emotions and encoding the ‘value’ of experiences. Unsurprisingly, it has been identified as a key area in studies of gambling.

However, it has also been previously found to correlate with ratings of pleasantness of smells, tastes and even music.

Interestingly, there was no difference in the brain areas directly related to experiencing taste, and the researchers suggest that the belief that the wine is more expensive probably doesn’t directly change our sensory experience, but leads us to think that the experience is more ‘valuable’.

The results echo behavioural studies which have found that the same wine is rated differently when served in different quality bottles.

pdf of full-text paper.
Link to write-up from The Times.

The psychology of the moral instinct

The New York Times has a fantastic in-depth article by Steven Pinker on the origins of morality and the psychology of moral reasoning.

It’s a comprehensive and enjoyable review of most of the main areas of the recently invigorated ‘moral psychology’ field.

As well as discussing how lab-based studies are helping us to understand the cognitive neuroscience of moral reasoning, it also contains a number of examples and thought experiments that bring the anomalies in our moral cognition into sharp relief.

Pinker argues that we have a specific reasoning framework for moral situations and that when we deem a situation to have moral implications, this comes into play.

The starting point for appreciating that there is a distinctive part of our psychology for morality is seeing how moral judgments differ from other kinds of opinions we have on how people ought to behave. Moralization is a psychological state that can be turned on and off like a switch, and when it is on, a distinctive mind-set commandeers our thinking. This is the mind-set that makes us deem actions immoral (“killing is wrong”), rather than merely disagreeable (“I hate brussels sprouts”), unfashionable (“bell-bottoms are out”) or imprudent (“don’t scratch mosquito bites”).

Pinker suggests that this process can easily be seen at work, as some things that were previously thought to be an personal difference have now become a moral issue (e.g. smoking) whereas other things that were previously thought to be a moral issue have now become a personal difference (e.g. atheism).

He also covers the development of morality in children, the role of genetics, and the anthropology of morality – how the hypothesised universal moral principles express themselves differently across different cultures.

Highly recommended if you want a guide to this burgeoning area of research.

Link to NYT article ‘The Moral Instinct’.

Nature NeuroPod visits SfN megaconference

Nature Neuroscience’s NeuroPod podcast has a special on the recent Society for Neuroscience annual megaconference that picks up on some of the more interesting new developments.

There’s loads of fascinating new findings in there, but don’t miss the last few minutes of the podcast where Prof Eleanor Maguire talks about ongoing work with London Taxi drivers.

Maguire’s team famously discovered in 2000 that London Taxi drivers have bigger than average hippocampi, a brain structure known to be heavily involved in learning routes and spatial representations.

The study found that the size of the hippocampus correlated with the length of time being a taxi driver, suggesting that the extensive training and navigational experience may change and develop the hippocampus.

The study won an Ig Nobel Prize in 2003 for research “that cannot, or should not, be reproduced” but was actually one of the first studies to show likely experience-related changes to the structure of the human brain.

In the podcast Maguire discusses a new study which updates the findings and suggests that the taxi drivers’ pumped hippocampi come at a cost.

While their navigational abilities were increased, their ability to learn new associations between things (another function of the hippocampus) was poor, and the size of the anterior hippocampi (a more forward area) was actually smaller.

This suggests that overdevelopment in one area of the hippocampus may actually reduce development in another.

mp3 of NeuroPod special at SfN 2007 conference.
Link to NeuroPod index page.
pdf of Eleanor Maguire’s Taxi driver update study.

Fighting over inner experience

Salon has an entertaining review of the new book Describing Inner Experience which is sort of a combination of an argument and a self-consciousness showdown between philosopher Eric Schwitzgebel and psychologist Russell Hurlburt.

Schwitzgebel is sceptical that we can accurately describe our inner thoughts and experiences, while Hurlburt feels that we are capable of doing so, when properly directed.

If you think that it’s obvious we can describe our inner mental states, start by reading the review and you’ll get a flavour of what the problem is.

At the beginning of the book’s central section, Hurlburt and Schwitzgebel meet their volunteer. Her pseudonym is Melanie. She is in her 20s, and she has an interest in psychology but no experience in these debates. Hurlburt explains the rules to her: She will simply tell them what was on her mind just before each beep, and they will try to figure out if her reports are accurate.

Hurlburt handles the direct questioning, then turns her over to Schwitzgebel for cross-examination. They have six sessions, each about an hour long. And over the course of these sessions, something unexpected happens, a novelistic twist that is subtle, hilarious and hard to describe. A battle for interpretive credibility emerges, as the doubt Schwitzgebel casts upon Melanie’s self-understanding rebounds upon himself.

The preface and first chapter of the book are freely available online if you want to learn more, and the book itself has just been published.

Link to Salon review.
Link to details of book and sample preface and chapter.

The art of first impressions

Frontal Cortex has found an absolutely fantastic video art piece that explores the psychology of first impressions.

It really brings home the fact that first impressions vary so much between individuals and can be vastly wide of the mark as character judgements.

The piece is by film-makers Lenka Clayton and James Price.

The pair also created the fantastic short film People in Order, another very simple premise which is a perceptive look at how people change as they age, and New Love Order, which briefly introduces us to couples arranged in the order of the length of their relationship.

All insightful pieces that are alternately, challenging, poignant, funny and original.

2008-01-11 Spike activity

Quick links from the past week in mind and brain news:

A neuroimaging study on ESP! The Neurocritic looks at a recent study that investigated parapsychology using brain scanners.

Drug companies approximately spend $30 billion dollars promoting drugs in the US – twice as much as they spend on research and development, according to a new study in PLoS Medicine.

Scientific American reviews the year in robots. To the bunkers!

Sociologist Laura Maria Agustin argues that double standards in how we think about rich and poor people who cross borders is clouding the debate on ‘sex trafficking‘ in Reason magazine.

Harvard Magazine has an article on the genetics of autism and why the condition is being increasingly thought of a spectrum of traits rather than a cut-and-dry diagnosis.

Mirror Neurons – Rock Stars or Backup Singers? Neuroscientist Gregory Hickok argues against the mirror neuron hype on SciAm’s Mind Matters blog.

Professor of Robert Sylwester is interviewed on Sharp Brains on the cognitive science of learning.

Could a computers have a conscience? The Buffalo News ponders the possibilities.

PBS has a full programme and website on the debate over the increasing trend for medicating children with psychiatric drugs.

An article in Wired argues that the next victim of climate change will be our minds.

New hope for tinnitus sufferers as BBC News article discusses some new treatments in the pipeline.

Intelligence and working memory may be the key to identifying the genes for schizophrenia, suggests new research.

Furious Seasons has a careful analysis of one of the most important studies of treating depression yet completed.

How do we know we’re not dreaming? Eric Schwitzgebel looks at the possibilities.

Cognitive Daily has a fascinating article on whether your name affects your performance and preferences (something known as nominative determinism).