The Entirely Legitimate Encephalon #67

(Updated! New post from Channel N -see below.) Welcome to the 67th edition of Encephalon, the regular neuroscience and psychology blog roundup. In honor of the recently revealed hilarious petty corruption in British politics, I demanded a hefty bribe to do this post... Wait, did you just read that? I'll give you £50 if you keep quiet about it. Ok, £100. I've got a reputation to uphold.
Anyway, in no particular order - certainly not in the order of the sum they paid me - here are your links for this edition:

• New! Channel N features a talk by MacArthur Genius and neuro-robotics pioneer Yoky Matsuoka. If you ever want a bionic limb, she's the person to call.
  
• In honour of old St Paddy, PodBlack Cat deals with the psychology of "luck", superstition, and Irish movies. Apparantly, there are now breeds of clovers which always have four leaves - where's the fun in that?
  
• Neurophilosophy's Mo writes about a pair of fascinating neuroimaging studies about limb amputation and the brain's construction of the body image.
  
• Ward Plunet of BrainHealthHacks has three recent posts looking at possible links between obesity and cognitive ability - could be controversial.
• Ouroboros discusses an interesting discovery which reveals another piece of the puzzle about the genetics of familial Alzheimer's disease.
• Hesitant Iconoclast of the NeuroWhoa! blog presents a well thought out two-part post about the search for the brain's "God Spot", and what it might mean if there isn't one.
• The Neurocritic is, as ever, critical, about lie detection and about the latest potential weight loss pills.
  
• SharpBrains, the homeland of Encephalon, has a useful set of links to the best brain health articles from the past month, and also discusses the deeply unhealthy goings-on at JAMA regarding conflicts of interests, an antidepressant trial, and some impressive academic fisticuffs.
• Neuronarrative discusses two fMRI studies which are rather topical in the current economic climate. One is about what happens when we take expert's advice when making decisions and the other about the "money illusion". Finally, there's a post featuring four expert responses to the Susan Greenfield Facebook-destroys-the-brain controversy (which I wrote about previously) which are rather enlightening.
• BrainBlogger provides a typically accessible write-up of a small but exciting study about the possible utility of lithium in Lou Gherig's disease, and a large study of the possible cognitive consequences of the metabolic syndrome.
• Finally, The Mouse Trap's Sandeep has an extensive and very thought provoking two part series of thoughts on the psychology of pleasure, pain and bipolar disorder, and to round out this issue, discusses an imaging study about how we know the difference between reality and fiction. Did I really accept bribes to produce this issue?

That's it for this issue! The next Encephalon is slated to be hosted over at Ouroboros, so get writing and e-mail submissions to encephalon{dot}host{at}gmail{dot}com by April 13th.

Cosmic Ordering, CAM and the NHS

A while back, I argued that it might not be a good idea to encourage the use of therapies, such as homeopathy, which work via the "placebo effect". (I've also previously said that what people call "the placebo effect" very often isn't one).

But there's more to say on this. Let us assume that homeopathy, say, is nothing more than a placebo (which it is). Let's further assume that homeopathy is actually quite a good placebo, meaning that when people go to see a homeopath they generally leave feeling better and end up experiencing better health outcomes - for whatever reason. This second assumption is exactly that, an assumption, because to my knowledge no-one has done a study of whether people who use homeopathy actually feel any healthier than they would if they had never heard of homeopathy and just got on with their lives. But let's assume it works.

Now, does this mean that homeopathy is a good thing? Well, sure, if it makes people feel better, it's a good thing. However - it doesn't follow that homeopathy, or any other form of complementary and alternative medicine which works as a placebo, should be available on the NHS. Many have argued that if CAM works, even if only by the placebo effect, it's still a useful thing which the NHS should support if patient's request it. I disagree.
A while back, South Bank University in London was widely mocked for getting a psychic to give a training session on "cosmic ordering". Cosmic ordering is the belief that you can get what you want in life by placing an order with the universe in the form of wishing really hard and then some quantum stuff happens and - I can't write any more of this. It's all crap. Anyway, the head of South Bank defended the session on the grounds that the staff requested it, liked it and found it useful.

Now if I applied for funding from my University to pay for a night down the pub for the whole of my Department I'd get the beaurocratic equivalent of a slap in the face. This despite the fact that people would enjoy it, it would help with team-building, and reduce stress levels. The point is that despite a Departmental night down the pub being, probably, a good thing in many ways, it's just not the kind of thing a University is responsible for. It would be incredibly unprofessional for University money to be spent on that kind of thing.

Likewise, it was unprofessional of South Bank to pay for a psychic to give a training course, even though the attendees liked it. Sorry to sound anal but Universities don't exist to give their staff what they want. They exist to pay their staff in exchange for their professional services & to help them carry out those services.

Likewise, the NHS, I think, doesn't exist to make people feel good, it exists to treat and prevent medical illnesses. So people like homeopathy and find it's helpful for relieving stress-related symptoms. Does that mean the NHS should be paying for it? Only if you believe that the NHS should also be paying for me to take a holiday to Thailand. I don't believe in homeopathy, but I do believe that a week on a Thai beach would do wonders for my stress levels. Or maybe I'd prefer a sweet guitar - I find playing guitar is great for relaxation, but it would be even better if I had a £700 model to play on. My well-being levels would just soar, if only until the novelty wore off. You get the point.

Most "complementary and alternative medicine" is medicine in appearance only. Just because homepaths hand out pills doesn't mean that what they do has anything to do with medicine. It's ritual. It's close to being entertainment, in a sense - which is not to belittle it, because entertainment is an important part of life. I'm sure there are many people for whom their sessions with their homeopath are really very useful. I just don't think the medical services should necessarily be paying for everything that people find helpful.

[BPSDB]

Encephalon #67 is coming...

ENCEPHALON, the regular psychology and neuroscience blog carnival, will shortly be arriving at Neuroskeptic. The last few editions were awesome, so don't let me down here - get writing, or get submitting things you've already written, about the brain, the mind, and all that kind of thing.

As always, please email submissions to encephalon{dot}host{at}gmail{dot}com by the 30th March.

Serotonin, Hallucinations & Psychosis

Serotonin, as every newspaper reader knows, is the brain's "feel good chemical". Of course, it's a little bit more complicated than that. A lot more complicated, in fact. But even amongst scientists who are aware of the complexity of serotonin pharmacology, the functions of serotonin are still generally thought of in the context of mood and emotion.
What everyone tends to forget is that serotonin has a wild side. There's a long line of research, stretching back to the 40s, on the role of serotonin in perception and hallucinations.

It all started on Bicycle Day - the 1943 day that Albert Hofmann first experienced the psychedelic effects of LSD ("acid") while riding his bike home from the lab where he first synthesized the drug. Serotonin was discovered in 1948. It was soon noticed that the chemical structure of LSD bears a striking similarity to serotonin - as does psilocybin, the major psychoactive ingredient in "magic mushrooms":You don't need to be a chemist to appreciate the resemblance. So it would be a very reasonable assumption that hallucinogenic drugs work by interfering with the brain's serotonin pathways, and therefore that the serotonin system is somehow involved in regulating thought and perception. Somehow, LSD inteferes with the serotonin system in the brain to cause profoundly altered states of conciousness. That's pretty important.That's also the easy bit. What's been difficult has been working out what hallucinogens actually do in the brain specifically, and how this produces their psychoactive effects. Trends in Pharmacological Sciences has a nice review article on this. To cut a long story short, we still don't know how LSD works, although since research has mostly dried up since the 1970s (everyone's studying happy pills now) this isn't all that surprising.

What has emerged is that LSD and similar compounds all activate the 5HT2A receptor. Interestingly, so do drugs which are chemically rather different, but with similar hallucinogenic effects, such as mescaline, favored by Native Americans and Matrix fans alike. The more potent a drug is at activating the receptor, the less of it you need to take to trip out.

So, does this mean that 5HT2A = hallucinogenic effects? The problem with this nice simple theory is lisuride, a potent 5HT2A agonist with no hallucinogenic effects at all. This troublesome result might not disprove the 5HT2A theory, however, in the light of a 2007 experiment finding that LSD has different effects on target cells from lisuride, despite them both binding to the same receptor. Presumably LSD and lisuride do subtly different things to the same receptors (read the paper for a more detailed account).

There's loads more to be said about hallucinogen pharmacology, and I'll be covering some of it in the future. What's interesting - and frustrating - is how few psychopharmacologists are aware of the field. A lot of hallucinogen research is really groundbreaking; the finding that two different agonists of the same receptor can have quite different effects is a really important one. It's certainly a humbling result. After Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior, it's impossible not to get to wondering whether other receptors in the brain might have equally complex lives. Hallucinogen research underlines how imperfect our current understanding of the brain is. Plus, hallucinogens are really a lot sexier than antidepressants. Given all of which, it's a shame so few scientists are studying them. Acid - it's not just for ageing hippies.

Link Erowid.org has made available Hofmann's personal archive of over 4,000 papers relating to LSD. A dream come true if that kind of stuff floats your boat & well worth a browse for historical interest.

M GEYER, F VOLLENWEIDER (2008). Serotonin research: contributions to understanding psychoses Trends in Pharmacological Sciences, 29 (9), 445-453 DOI: 10.1016/j.tips.2008.06.006

González-Maeso, J., Weisstaub, N., Zhou, M., Chan, P., Ivic, L., Ang, R., Lira, A., Bradley-Moore, M., Ge, Y., & Zhou, Q. (2007). Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior Neuron, 53 (3), 439-452 DOI: 10.1016/j.neuron.2007.01.008

Nature "Does" Science Communication

The past few weeks has seen Nature (and Nature Neuroscience) run a series of features about science communication - science journalism, science blogging, and so on. They're all worth reading, and very readable, but, perhaps inevitably they raise more questions than they answer.

The basic assumption behind all of the articles is that communicating science to the public is A Good Thing, and scientists should be trying to help with it - whether by blogging about science, or helping to write press releases, or talking more to journalists.
I'm not sure about this. Sure - good, accurate information about science should be available to anyone who looks for it. But the same goes for history, or politics, or cricket. If people want to know about something, they should be able to read good stuff that's been written about it. I think there is an awful lot of great science writing out there, both in books, in print, and online. You can never have enough of it, though, so scientists should certainly be encouraged to write about science or help others to write about science in this way.

What I find questionable, though, is the idea that people who aren't really interested in science should be the targets of science communication. The Nature editorial of 19th March warns that

An average citizen is unlikely to search the web for the Higgs boson or the proteasome if he or she doesn't hear about it first on, say, a cable news channel. And as mass media sheds its scientific expertise, science's mass market presence will become harder to maintain.

Which is true, but I can't help but ask, why should the average citizen know or care about the Higgs boson? I find the Higgs boson quite interesting, although I admit, not as interesting as the brain. But I don't think that everyone should share my tastes. Personally, I find cricket deadly boring; I've never read the cricket pages of the newspaper, and I don't think I ever will. But some people are really into it, and good for them. If you prefer cricket to particle physics, who am I, or the editors of Nature, to say that's a problem?

The obvious response to what I've just said is that in a democracy, people have to know about science, because a lot of the major challenges facing our society involve science. If the public are ignorant about science, we won't be able to deal effectively with, say, climate change. There's probably some truth in that, but I suspect it's more important to educate people about climate change specifically, than to try to get them interested in Higgs bosons and hope that their passion for physics somehow "spills over" into a concern for the environment.

So, personally, I'm not really concerned if the public aren't interested in science. What concerns me is when they're actively fed inaccurate information about science. This just my personal take, but I would far rather that the newspapers never run another story about neuroimaging, say, than they keep on running rubbish ones.

Nature (2009). It's good to blog Nature, 457 (7233), 1058-1058 DOI: 10.1038/4571058a

Brumfiel, G. (2009). Science journalism: Supplanting the old media? Nature, 458 (7236), 274-277 DOI: 10.1038/458274a

Nature (2009). Filling the void Nature, 458 (7236), 260-260 DOI: 10.1038/458260a

Nature Neuroscience (2009). Getting the word out Nature Neuroscience, 12 (3), 235-235 DOI: 10.1038/nn0309-235

Nemesysco Strike Back, in Press Release Form

You may remember the case of Nemesysco. They're the company who market software which they claim can read your emotions from the sound of your voice. A few weeks ago, Nemesysco threatened legal action over a paper by two Swedish academics, Lacerda and Erikkson, which was critical of their products amongst others. A number of bloggers were moved to comment on this.

Anyway, I've just recieved an email from "Yossi Pinkas, VP Sales & Marketing, Nemesysco Ltd." with an attached Press Release containing Nemesysco's response to the controversy. Nemesysco apparantly read this blog, since they quote me in it. Hi, Nemesysco!

The Press Release doesn't appear on their website (yet), so I've uploaded it to scribd. Comments to follow.

"Ephebiphobia" is worse than ever!

The Guardian has a somewhat interesting if very self serving article by psychologist Tanya Byron about "ephebophobia" or the fear of tearaway youth. She begins with a pithy observation, namely that adults have been complaining that the kids these days have no respect, since time immemorial:

"We live in a decaying age. Young people no longer respect their parents. They are rude and impatient. They frequently inhabit taverns and have no self-control." These words - expressing the all-too-familiar contemporary condemnation of young people - were actually inscribed on a 6,000-year-old Egyptian tomb.

In other words, every generation thinks that the next generation is the worst ever. That's an excellent point. Yet she somehow missed the irony in the next line:

Such quotes illustrate what I believe has become a historically nurtured and culturally damaging phenomenon: ephebiphobia - the fear of youth. But today this problem is worse than ever.

Is it really? Or is there another Egyptian tomb somewhere, yet to be uncovered, in which someone laments how silly modern Egyptians are for thinking that everything was better in the good old days?

Amphetamine, Cocaine and DAT

The brain is a tightly regulated system. Levels of neurotransmitters, for example, are regulated by reuptake proteins, which move transmitters from outside the cell to inside, where they are inactive. This means that after cells release a neurotransmitter, such as dopamine, it is rapidly taken back up again.

Interestingly, however, the levels of the reuptake protiens themselves are variable and can change in response to various things. If dopamine levels rise, for example, nearby cells rapidly increase the number of dopamine transporters (DAT), thus helping to reduce dopamine levels again. This happens when DAT proteins waiting dormant within nerve cells are sent to the surface (the cell membrane) in response to increased dopamine levels.

This much is fairly well known, but a lovely experiment from a University of Michigan team has revealed just how fast the process is. (Dopamine and Amphetamine Rapidly Increase Dopamine Transporter Trafficking to the Surface: Live-Cell Imaging Using Total Internal Reflection Fluorescence Microscopy).

The authors used a form of light microscopy which allows the membrane of a single cell to be imaged. They created cells genetically engineered to have dopamine transporter protein (DAT) which glows, because it was linked to Green Fluorescent Protein. This allowed them to view changes in the level of DAT on the surface of the cells, in real time, in living cells.

They found that adding dopamine caused DAT levels to rise astonishly fast - within just a few seconds. Amphetamine, a drug which acts on the DAT, had the same effect. However, cocaine, a drug which blocks DAT, prevented this effect.They've even made a video so that you can see the dopamine transporters bubbling up on the surface of a single cell. Watch it (if you have academic access) - it beats 99% of YouTube.

This is a fascinating result, and it underlines the fact that nothing in the brain is ever straightforward. For example, most people will tell you that amphetamine and cocaine both have stimulant effects by "increasing dopamine levels" - cocaine by blocking dopamine reuptake and amphetamine by causing the dopamine transporter to actually go into reverse and start releasing dopamine. But this result suggests that amphetamine also increases membrane dopamine transporter levels. That could have any number of indirect effects. Then again over longer time-scales (minutes), amphetamine reduces the DAT levels. That could have indirect effects too...

It's also worth bearing in mind that although this experiment involved the dopamine transpoter, other reuptake proteins like the serotonin transporter might well be regulated in the same way, which could have big implications for antidepressant action...

Furman, C., Chen, R., Guptaroy, B., Zhang, M., Holz, R., & Gnegy, M. (2009). Dopamine and Amphetamine Rapidly Increase Dopamine Transporter Trafficking to the Surface: Live-Cell Imaging Using Total Internal Reflection Fluorescence Microscopy Journal of Neuroscience, 29 (10), 3328-3336 DOI: 10.1523/JNEUROSCI.5386-08.2009

In Defense of Susan Greenfield

Baroness Susan Greenfield has been taking a lot of flak these past few days for her comments about Facebook and computers in general:

If the young brain is exposed from the outset to a world of fast action and reaction, of instant new screen images flashing up with the press of a key, such rapid interchange might accustom the brain to operate over such timescales. Perhaps when in the real world such responses are not immediately forthcoming, we will see such behaviours and call them attention-deficit disorder...

and

I often wonder whether real conversation in real time may eventually give way to these sanitised and easier screen dialogues, in much the same way as killing, skinning and butchering an animal to eat has been replaced by the convenience of packages of meat on the supermarket shelf

She's taken a lot of flak, and she fully deserves it. Her comments were ill-judged and they bring her position as head of the Royal Institution into disrepute. Her speculations about clinical diagnoses such as ADHD and autism were especially dubious.

Greenfield's statements also display the vacuous obsession with "The Brain" so common today - if she'd simply said that spending hours on the internet might plausibly make kids grow up anti-social, that would be fair enough, but she had to bring the brain into it (several times in her various comments). Hence the headlines to the effect that Facebook could change or damage the brain. Well, Facebook does change the brain - as does everything else - because every experience we have has an influence somewhere in the brain. I'm reminded of Vicky Tuck on boy's and girl's brains; Tuck, however, is not a neuroscientist. Greenfield should know better.

But despite all this, Baroness Greenfield does make an important point.

At the moment I think we're sleepwalking into these technologies and assuming that everything will shake down just fine

These are very wise words. As a society, we are in danger of "sleepwalking" into social and cultural changes which we may end up regretting. Profound changes in the way people live rarely happen overnight, and they are rarely presented to us as a choice that we can either accept or reject. Societies just change, over a span of decades, often without anyone noticing what is happening until the change has happened.

One of my favorite books is Bowling Alone by the sociologist Robert D. Putnam. Putnam assembled data from a wide range of sources to support his theory that a profound change took place in America over the years from about 1960 to 1990; namely, that Americans stopped participating in community life. Union membership, Church attendance, charitable giving, league bowling, voter turnout, cards-playing, and many other such statistics fell markedly over this period, after a high peak in the 1950s. Meanwhile, solitary or small-group activities such as TV watching, spectator sports, and so on, exploded. Over the span of 20 years or so, Americans lost interest in "the community" as a whole and turned to themselves and their immediate circle of friends and family. He also makes a convincing case that this is, in many ways, a bad thing.

I doubt that Putnam's thesis is water-tight; for all I know he may have cherry-picked those statistics that support his theory and ignored those that don't. It wouldn't be the first time that someone has done that. Yet what's interesting about Bowling Alone is that even if Putnam's theory is only part of the truth, it's hard to deny that there's something in it - but it still took a book published in 2000 to bring it to people's attention. Putnam was writing about profound changes that every American will have felt to some degree. Yet these changes went un-noticed, or at least, few noticed that the various individual changes were part of a larger trend.

Putnam proposes various causes for the fragmentation of American community life, ranging from suburbanization to the increasing time pressures of work to that old favorite "the breakdown of the family". None of these were deliberate choices. Over 20 years or so America sleepwalked into a different way of life. This is hard to deny even, if you don't accept everything Putnam says. Baroness Greenfield, clearly, is no Robert Putnam. But her point about the dangers of sleepwalking is a sound one. Sleepwalking happens. It would be a pity if that message were to be lost in all the nonsense about Facebook and the brain.

[BPSDB]

Antidepressants, Placebos and the Failure of Psychiatry

Update 06 05 2009: Time readers may find this other post interesting!

Antidepressants are some of the most-prescribed drugs in the world. Yet they are also amongst the least well understood. We know little about how effective antidepressants are in the people who take them. Some antidepressants may work fantastically for most people. On the other hand some of them, perhaps all of them, may be useless or even worse. The truth is unclear.This is a minority view. Opinions about antidepressants are polarized - most people either firmly believe that they do work, or firmly believe that they don't. Yet neither of these positions seems to me to be supported by the evidence available. I don't think that anyone ought to firmly believe anything about these drugs - except that better research is urgently needed.

Another placebo meta-analysis

The issue is not a lack of studies. After fifty years of research, and untold millions of research dollars, there are hundreds of published clinical trials of antidepressants. It's when you try to make sense of the results of this great mass of trials that the problems become apparent. The latest attempt to do that is a paper from a German-American collaboration, Rief et. al.'s Meta-analysis of the placebo response in antidepressant trials. The authors set out to

Determine overall effect sizes of placebo and drug effects in antidepressant trials

In other words, they wanted to find out how much people improve when given antidepressants, and how much of that improvement is due to the placebo effect. They had plenty of data to work with. Even after discarding hundreds of trials for being too small or otherwise unsuitable:

The final sample consisted of 96 trials that reported sufficient data to compute effect sizes. The placebo groups of these studies comprised 9566 people. Approximately half of the studies were published after 1996, 68% were conducted in the United States, and the mean sample size was 86 participants.

And this is what they found after crunching the numbers:

The overall effect size [Cohen's d] of the placebo effect was 1.69 (95% CI=1.54–1.85), as compared to d=2.50 (95% CI=2.30–2.69) in the drug group. The ratio of the effect sizes suggests that 67.6% of the improvements in the drug group were attributable to the placebo effect [i.e. because 1.69 is 67.6% of 2.50].

That seems like a nice, neat and tidy result. When you give depressed people antidepressants, they get loads better (a standardized effect size of 2.50 is enormous), but most of that enormous improvement is due to the "placebo effect". However, the truth is not quite so neat.

It's a Little Bit More Complicated Than That

1. First off, none of the studies included in this analysis measured the placebo effect. The "placebo effect" is supposed to be the power of treatments to make people get better purely through making them expect to get better. It's certainly plausible that there could be big placebo effects in depression. There is plenty of anecdotal evidence that it happens.

In these studies, patients took either antidepressant pills or sugar pills. The patients given sugar pills were assessed as having got a lot better, on average. Is that evidence for the placebo effect? No, because as I've explained before, the improvement reported in the placebo group could be huge even if there were no "placebo effect" at all. The patients might have just got better spontaneously, because people who are depressed do tend to get better with time. It might have been that old chesnut, regression to the mean. Or maybe the patients only seemed to get better on average because the ones who didn't get better dropped out of the trial.

According to a meta-analysis of trials which actually did examine the placebo effect - by comparing people given placebos to people who got no treatment at all - the placebo effect in depression is at best small (Hrobjartsson & Gøtzsche 2004). However, the authors of this paper are well known for being very skeptical of placebos, and the number and quality of the trials was very low. There were 7 trials with a total of 258 patients. That's it. The only reasonable view is that we just don't know how powerful placebos are in depression.

2. Rief et. al. found that the size of the effects of antidepressants and placebos was much bigger when using "observer-rating" to measure the severity of depression, as compared to when patients rated their own symptoms. The difference between the two types of rating scale was enormous, dwarfing the drug vs. placebo difference:

In the placebo groups, there was a substantial difference between effect sizes for improvements rated by observers (d=1.85; 95% CI=1.69–2.01; 93 studies) compared to those rated by patients (d=0.67; 95% CI=0.49–0.85; 28 studies)...The difference between self-ratings and observer ratings was also found in the drug groups (self-rating d=1.12 versus observer rating d=2.89).

What does this mean? It could mean that psychiatrists tend to exaggerate small changes in their patients' depression. But it could mean that depression renders people unable to notice their own improvement. Perhaps the commonly used self-rating questionnaires, like the BDI, are just not very good at measuring depression, while observer rating scales, like the HAMD, are better. On the other hand it could be that self-rating scales are better, and observer-rating scales tend to exaggerate changes. Or...

Any or all of these could be true. Speaking as both a sufferer from depression and as a trained depression observer (I use the HAMD for research), I can confidently say that rating depression is one of the hardest things I ever have to do. Monitoring my own ups and downs, let alone putting a number on them, is extremely difficult. Trying to put a number on the mood of a patient who I've only known for an hour is even harder.

Poets and novelists struggle mightily to capture the purely qualitative aspects of our emotions. The idea that some guy reading a list off a printed list of questions could succeed at putting a number on a stranger's wellbeing in 5 minutes seems faintly absurd.

3. The results of this meta-analysis are much more favorable to antidepressants than was the analysis of Irving Kirsch et. al. (2008), Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. This was the (in)famous paper that everyone in the media thought proved that "Prozac doesn't work".

Kirsch et. al. reported an average difference between the drug improvement and the placebo improvement of d=0.32, as against d=0.81 in this study. Conventionally, a standardized effect size d of 0.3 would be called "small" while 0.8 would be called "large". So this is a big difference. Why?

Again, there are plenty of possible reasons. Kirsch et. al. included fewer trials - only 35 -and only considered "newer" antidepressants. Rief et. al. included trials of older drugs. Kirsch et. al. included unpublished drug company data; Rief. et. al. only included published trials, meaning that publication bias could have been a problem (although they say that there is no evidence it was.)

Differences in the statistical techniques used could also explain it. As a series of outstanding posts by P J Leonard and Robert Waldmann last year showed, there were serious problems with the Kirsch et. al. analysis; these are too technical to go into here but suffice it to say that if the authors of this analysis had chosen to use Kirsch et. al.'s methods they might have reached very different conclusions.

4. The most important message of Rief et. al.'s analysis is also the simplest. There are vast differences between trials in terms of what happened to the patients.
This is a plot of the degree of improvement experienced by patients in the placebo group in each trial. The average improvement ranges from zero to huge. In addition, more recently published trials tended to find greater improvements. Yet all of these patients were given the exact same thing - sugar pills. (This is not a new finding.)

Clearly, something is seriously wrong here. People suffering from the same disease given the same treatment should show similar responses. The most likely explanation is that these groups of people were not all suffering from the same disease. The diagnosis of "major depression" is increasingly seen as problematic; almost certainly there is in fact no single disease called "depression" at all. Yet every antidepressant clinical trial operates under the assumption that there is one.

Given this, it's no wonder that antidepressants, and placebos, give such wildly different results in different trials. The wonder, perhaps, is that we are still conducting such trials without first establishing what exactly we think clinical depression is and how best to measure it.

[BPSDB]

Winfried Rief, Yvonne Nestoriuc, Sarah Weiss, Eva Welzel, Arthur J. Barsky, Stefan G. Hofmann (2009). Meta-analysis of the placebo response in antidepressant trials Journal of Affective Disorders DOI: 10.1016/j.jad.2009.01.029

More on Voodoo Correlations

I just want to draw your attention to Brad Buchsbaum's blog, where he has two truly excellent posts(1,2) on the Vul et. al. (2009) Voodoo Correlations in Social Neuroscience paper.Here's hoping there will be plenty more to follow...

My take on this paper is here.

A Very Optimistic Genetics Paper

Saturday saw the Guardian on fine form with a classic piece of bad neuro-journalism which made it all the way onto the front page:

Psychologists find gene that helps you look on the bright side of life
Those unfortunate enough to lack the 'brightside gene' are more likely to suffer from mental health problems such as depression

What the research actually found was nothing to do with looking on the bright side of anything, and was nothing to do with depression either. In fact, it suggests that the gene in question doesn't cause mental health problems. So the headlines are a little misleading, then.

The study comes from Elaine Fox and colleagues from the University of Essex.* They took 111 people, presumably students, and got them to do a "dot-probe" task. Performance on this task was related to the genotype of the 5HTTLPR polymorphism, a variant in the gene which encodes for the serotonin transporter protein. Serotonin is "the brain's main feelgood chemical" as the Guardian put it... except it isn't, although it does have something to do with mood.

What's a "dot probe" task? It's a test which has become popular amongst all kinds of psychologists over the past 10 years or so, having first been used in 1986 by Colin MacLeod et. al. The task involves pressing a button whenever a "probe" - a little dot - appears on a screen. The goal is to press the button as quickly as possible, as soon as the dot appears.

The twist is that as well as the dots, there are other things on the screen. In the 1986 version of the test these were words, while in this experiment they were colour pictures. Some of the images were pleasant: smiling faces, flowers, and other nice things. Some were unpleasant - scary dogs, bloody injuries, etc. And some were neutral objects, like furniture.Pairs of these pictures appeared on the screen for a short time (half a second) immediately before each dot appeared, one on the left of the screen and one on the right. The key is that the dot appeared in the same place as one of the pictures.

The task operates under the assumption that if the viewer's attention is grabbed by one of the pictures, they are likely to be faster to respond to seeing the dot when it appears in the same place as that picture, because they will already be focused on that area of the screen. If, for example, people are on average faster to detect the dot when it appears in the same place as the nice pictures as opposed to the horrible ones, this is described as indicating a "positive attentional bias" i.e. an unconscious tendency to pay attention to pleasant pictures.

Unfortunately, now that you know what a dot probe task is, you can't take part in any psychology experiments which uses one, because once you know how it's supposed to work there's no point in doing it. Sorry. But on the bright side, you now officially know more about psychology than The Economist, whose write-up of this experiment managed to be even worse than the Guardian's. They not only sensationalized the results, but also misunderstand the whole point of the dot-probe task - it's not about "distraction", it's about selective attention-grabbing.

Anyway, that's the task, and the study found that carriers of two "long" variants of the 5HTTLPR gene showed a strong attention bias towards nice pictures and away from nasty ones, while other people showed no biases. Statistically, the result was highly significant, so let's assume it's true. What does it mean? You could take it to mean that carriers of two long variants were more optimistic in that they tend to pay attention to the good stuff. On the other hand you could equally well say they're so squeamish and wussy that they can't bear to look at the bad stuff and have to avert their eyes from it.

And what's this got to do with depression? Well to cut a very long story short the gene in question has been previously linked to depression and also to personality traits such as "neuroticism" - being anxious, worried and generally miserable (see this paper). But in this study they found no such association with neuroticism. Despite the fact that it was a report of this association which got everyone interested in the 5HTTLPR variant in the first place back in 1996! Brilliantly, they spin their negative finding as a good thing -

The fact that our genotype groups were matched on a range of self-report measures, including neuroticism can be seen as a major strength.

Hope springs eternal. Overall, while this paper is a fine contribution to the psychology literature on the dot-probe task (and the results genuinely do seem to be very significant - there's probably something going on here) it's got nothing to do with optimism and little to do with anything that the average newspaper reader cares about. Luckily, we have journalists to make science interesting on the cheap and on the quick - at the cost of accuracy. There's a lot of really interesting, really thought-provoking popular science writing to be done about the dot-probe, and about the 5HTTLRP gene. But none of it has yet made it into the British papers.

[BPSDB]

*Fox, my PubMed search reveals, also does work on so-called "electromagnetic sensitivity". The upshot of her work is that lots of people sincerely believe that signals from mobile phones and other sources make them feel unwell, but actually, it's all the placebo effect. Now that really is something that everyone should find fascinating - much more so than this study, anyway.

Elaine Fox, Anna Ridgewell and Chris Ashwin (2009). Looking on the bright side: biased attention and the human serotonin transporter gene Proc. R. Soc. B

The Ethics of Junk Science

"Women, the weaker sex... at resisting food, researchers find".

This appeared in the Daily Mail a while back. This headline was based on a neuroimaging experiment, which, predictably, didn't prove anything of the kind. Yawn. I've written about this kind of thing before, and no doubt I will do again. But why do I do it? What's the harm in this kind of thing?

A cynic might say that this kind of thing is harmless fun - or at any rate, harmless. No-one really cares about articles like this, and no-one takes them seriously. No-one's going to read this article and start to think that all women are impulsive and gluttonous - at least not unless they were a sexist pig to begin with.

The opposite view is that this article represents a sexist attack on the rights and status of women (in this particular case), and more generally, that this kind of science writing promotes a reductionist view of life in which all of our problems are ultimately biological ones. This has the dangerous implication that our problems either can't be solved, or can only be solved through the application of some kind of pill or potion. Junk science writing of this kind, then, is actively dangerous.

Those are the two extremes. The truth, I assume, lies somewhere in between. No-one is going to read this one single article and become a sexist pig, just like this spectacularly awful article isn't going to make anyone hate hip-hop and no-one is going to listen to Baroness Susan Greenfield and decide they want to ban Facebook. It's just a couple of hundred words in the Daily Mail.

But while eating one packet of cookies won't make you overweight, scoff a packet every day and your waistline will suffer for it. Every crap science article in the newspapers is another portion of nonsense in the nation's diet; over time, it builds up. One simplistic, vaguely sexist popular science headline isn't going to do much harm; if that's all people read for years on end it's going to have an effect. And there are loads of them.

There's anothing point, though. Even if you don't have strong views on the particular issues at hand, you should care about the abyssmal standards of science journalism. I'm open to the idea that women are, on average, less able to restrain their hunger then men. It's probably not true, but I don't see that idea in itself as either implausible or inherently sexist. But what I do know is that it's a fairly difficult question. There are arguments on both sides. More generally, the controversy over human sex differences is a vast one, with a huge amount of evidence to consider, and it isn't going to be settled by one neuroimaging study, or even a hundred.

The implicit message of this kind of junk science writing is that all kinds of complex and difficult scientific questions are in fact really simple. If people were more aware of the difficulties inherent in answering even apparantly simple questions, they'd be less willing to settle for the easy, simple, entirely wrong answers when it comes to practical political and social issues.

Maybe that's too simplistic. But it wouldn't hurt.

[BPSDB]