Neuroskeptic Has Moved

After four years, Neuroskeptic is no longer an indie blog - I've moved to Discover Magazine blogs.

The new address is here: http://blogs.discovermagazine.com/neuroskeptic/

So please stop using this blogspot site; don't link to it, don't visit it, etc. All the posts are on the new one. The new RSS feed is: http://feeds.feedburner.com/neuro-skeptic/
Comments on this blog are now turned off but all old comments have been transferred to the new site, and you can comment there.

Neuroskeptic Is Moving

Over the next few days, Neuroskeptic will be moving to Discover Magazine. Which is very exciting.

This will mean no new posts for at least a week, while we sort out the technical issues of the transition, and I've also turned comments off - all existing comments will be moved over to the new blog, however.

For more updates you can follow me on Twitter...

See you on the other side soon!

How To Respond to Criticism

People argue. On the internet, especially. Here's some tips on how best to respond to criticism of your ideas or writing - in my experience (the fact that I've often failed to follow these rules myself is part of that experience.)

Be Nice

Aggressive and insulting responses are a sign of weakness, and readers know it. If you're confident in your position, you can afford to be nice, and it makes your whole case look more convincing. Quite apart from the fact that it's just, well, nice.

Don't call out people for not being nice, though. The Three V's - "vitriolic", "virulent" and "violent" - seem to be especially common complaints. The trouble is that just as remarking on someone's faux pas is, itself, a faux pas, proclaiming that your opponent is using nasty language lowers the tone of your response.

It's natural to feel hurt by insults, but keep your feelings to yourself. Even if the criticism really is appallingly vicious, let it speak for itself: just slip a quote of the worst bits into your response, by way of making a separate point, and don't lower yourself by commenting on it.

Complimenting critics shows strength. It shows that you're confident that, despite the praise you're heaping on them, you're still right. So be generous. It only works if it seems sincere, though, so no outright brown-nosing.

Be Fresh

Don't just defend the ground you've already occupied - take the offensive (without being offensive). Bring new arguments to the table. New facts are always good - if a critic tries to debunk an example you used to prove a point, don't bother to quibble with them: produce three more.

Make your response readable. A reply is a piece of writing like any other, and it should be as concise and as clear as possible. Exhaustive replies are counterproductive; they're unlikely to be read. Just identify the key criticisms, and respond to those.

Stick to the point. Readers want you to engage with the issues. You may feel that you know all about your detractors' beliefs, character, motives and so forth, and that these are interesting. They rarely are.

Be Right

Often forgotten, this one.

If you're not sure whether you're right, find out. Take your time. If you have to say something right now, say you're working on it. Better a late reply than a bad reply.

If you're wrong, admit it. People will forgive an honest mistake, if you hold up your hands and ask them to. A reputation for admitting your mistakes and correcting your views is actually a point in your favor

If you've done something wrong, apologize. And nothing more. Don't try and justify yourself; it never works. Don't try and get people to pity you; it'll ensure no-one does. Just say sorry, and then keep quiet until the whole thing cools down.

Notorious Paedophile Reads Neuroskeptic

There's been controversy in the UK over an article published in the Guardian that's regarded as being pro-child abuse.

In particular, the newspaper has taken flak for quoting Tom O'Carroll, a self-confessed paedophile and advocate for the right of people to be one. Amongst other things he's written a book about Michael Jackson. At least this week, until the next one comes along, he is Britain's most notorious paedophile.

Now oddly enough, I recently had an encounter with O'Carroll, although I didn't know who he was at the time. Here's the tale...

A few weeks ago, I got an out-of-the-blue email from a Neuroskeptic reader (as happens often), from someone saying he'd tried to leave a comment on this post but it was rejected for being too long.

O'Carroll (for it was he) wanted to know whether I agreed with his reservations about some research on "Cerebral white matter deficiencies in pedophilic men", and specifically on this statement by the paper's author:

One must consider carefully whether the brain differences we detected [i.e. reduced white matter volume in particular areas] cause pedophilia or whether some aspect of being pedophilic caused the brain differences...

Although it is now known that certain brain structures respond to environmental stimulation, such as the motor cortex, there is no evidence that such stimulation causes any changes in the superior fronto-occipital fasciculus or right arcuate fasciculus (the brain regions in which pedophiles and nonpedophiles differ).

Moreover, the brain regions we identified are extremely large, and no previous research has ever found changes in such large regions of the brain. As an analogy, physical exercise will generally stimulate one’s muscle tissue to grow, but one would not grow an extra arm; neurological changes occur only in a very specific manner.

O'Carroll thought that this is a misleading analogy, because the brain could be plastic in ways we don't yet understand. I agreed. We just don't know enough about the brain, yet, to say that the observed white matter changes can't possibly be responses to experiences.

Several recent studies found that experience and learning can change adult human white matter structure. The changes observed were fairly small, but then these studies were fairly short, so they don't define the upper limit of what's possible over time.

These results are not without critics of their own, and I'm on the fence about whether white matter is plastic at all, but my point is, it's an open question. So comparing the idea of white matter plasticity to 'growing an extra arm' is overstatement - and it would be, whether the topic was paedophilia or anything else.

Now, as I said, I hadn't heard of Tom O'Carroll at the time, and I assumed he had a purely academic interest in the matter, as an piece of oversold neuroscience. But now, thanks to the Guardian drama, I realize that...

Britain's most notorious paedophile reads Neuroskeptic.

Hmm.

On that macabre note, I've often wondered whether James Eagan Holmes, the Aurora, Colorado Batman shooter, ever visited this blog. It's possible: he was a neuroscience undergraduate and later PhD student over the time Neuroskeptic's been going.

There have been 574 visits from Aurora, Colorado, where Holmes was doing his PhD, since 2008. I'll never know whether he was one of them, but the idea that he might have been is pretty creepy.

Why (And How) To Write Less

I said a couple of times during my recent trip to UPenn that "Most writing is too long". People seemed to nod appreciatively at this, so here's some more on that topic...

Most writing is too long and the most common reason is that it's not written for the reader's benefit. Readers want the important stuff, as clearly as possible, in the shortest possible space. If you remember that and let it guide your writing, you won't go far wrong. The reader's favourite bits are the ones you don't write.

The problem is that it's tempting to write for your own benefit, not the reader's, and this almost always ends up making things too long. This can take many forms:

Some write to help themselves understand the material, such that the end product is a record of their learning process. Others will insert details that the reader doesn't need, because it's a topic the writer's fond of. Other fear making tough decisions about what to include, so they say everything and hope some of it's good: "Write it all and let God sort them out."

This is common because formal education teaches you to write poorly. Specifically, it encourages people to overwrite. Teachers and professors give assignments and they set a minimum word count. This sends the message that where writing's concerned, more is better.

Teachers have their reasons. They want a brain-dump to show that the student's done the homework, pretty much the opposite of good writing. That's fair enough for school, but if you internalize that philosophy, you will end up writing to show off rather than for the reader's benefit.

Once you put the reader's interests first, you'll naturally start to find your own ways to achieve that. Everyone's style is different, but here's a few I've learned:

• If it starts "On that note...", "Also...", or "Furthermore...", you should probably cut it.
• Join Twitter - writing to a 140 character limit is a great form of discipline. Then imagine that every paragraph you write must become a tweet. You may find you can compress that paragraph into one sentence.
• Just as Twitter is good, other artificial constraints are good. Set yourself a word limit; if you're blogging, make it 500 words.
• Unless the article's about you, sentences that include the word "I" or "we" can usually be cut.
• Think of your piece as a nuclear missile: it has a payload, the message you want the reader to grasp, and a rocket motor, the introduction and other stuff you need to ensure it reaches the reader. Every missile needs a motor, but designers try to make the payload as big as possible, given the size of the motor. Identify what your payload is, and what your motor is. Then think, is my motor too big? (It probably is.) In this paragraph the missile analogy is the motor.
• As a rule of thumb, by writing it better, you can cut it down by half.

Am I Attacking Neuroscience?

A New York Times article just out says:

Neuroscience: Under Attack

Under attack by who?

Er... me. And the rest of the usual suspects:

A gaggle of energetic and amusing, mostly anonymous, neuroscience bloggers - including Neurocritic, Neuroskeptic, Neurobonkers and Mind Hacks - now regularly point out the lapses and folly contained in mainstream neuroscientific discourse. 

I had promised not to do any more self-referential posts, but this one wasn't my fault. Just when I thought I was out, they pull me back in.

Anyway, I'm pretty happy with how Neuroskeptic's presented in the article, but not entirely.

The headline is sensationalist - I don't see myself as attacking neuroscience and I don't think any of the others do either. We are trying to defend neuroscience against errors and misrepresentations. My ideal is The Sceptical Chymist, where skepticism helped, rather than undermined, chemistry.

But the job of a headline is to be sensationalist so that's OK. Most of the piece is very good. I'm all on board with this:

Meet the "neuro doubters". The neuro doubter may like neuroscience but does not like what he or she considers its bastardization by glib, sometimes ill-informed, popularizers.

Yet I can't quite go along with this:

A number of the neuro doubters are also humanities scholars who question the way that neuroscience has seeped into their disciplines, creating phenomena like neuro law, which, in part, uses the evidence of damaged brains as the basis for legal defense of people accused of heinous crimes, or neuroaesthetics, a trendy blend of art history and neuroscience.

Admittedly this wasn't directly aimed at me because I'm not a humanities scholar, but I believe that neuroaesthetics and neurolaw are absolutely valid - in theory.

I'm not defending any particular manifestation of those, and I've criticized quite a few. But in the abstract, I see nothing wrong with neuroscience helping to explain those things. It will be difficult in practice, but it's fine to try.

Upcoming Appearances (And A Funny Picture)

Just a quick reminder - or perhaps a new announcement for those of you who aren't on Twitter - that I've been short-listed for the UK Science Blogging Prize. I'll be giving a very brief talk at the awards night next Sunday 25th November which is in the Penderel's Oak, London.

Speaking of Twitter, I'm on Twitter here: https://twitter.com/Neuro_Skeptic

I'll also be speaking in Philadelphia on December 6th at UPenn on the topic of Brain Rumors: Public (MIs)understanding of Neuroscience and Why It Matters

Finally, to save this from being a completely boring post, here is the cover of the latest British Medical Journal, which in my opinion is the funniest image ever to grace the front of an academic publication. Even if it is, literally, potty humour.

Migraines On Twitter

People talk about migraines on Twitter more on weekdays than weekends and holidays - and the peak time of day for the horrible headaches is 7 in the morning.

The working-day effect on migraines has been reported before - perhaps a reflection of stress or, less charitably, people wanting a day off work... although some people suffer weekend migraines.

Of the working week, Tuesdays saw the most migraines, while Fridays were the least bad. About 80% of Twitter migraine mentions came from women - which matches the fact that women are at higher risk.

That's according to a little study just published that used a public database of tweets, timeu.se, that Neuroskeptic readers may remember.

In fact, an author of this study said in an email to me that it was actually inspired by one of my posts... but I'm aware that telling you that, combined with the previous post, means I'm in danger of blowing my own trumpet or 'disappearing up my own arse' as we say in the UK. So rest assured that this will be the last such self-referential piece for at least... a day or two.

Linnman, C., Maleki, N., Becerra, L., and Borsook, D. (2012). Migraine Tweets - What can online behavior tell us about disease? Cephalalgia DOI: 10.1177/0333102412465207

Blogging's First Academic Paper

In an historic achievement, I can announce that I have become (to my knowledge) the first blogger ever to publish in a peer-reviewed academic journal under a blogging pseudonym.

Skeptic, N. (2012) The Nine Circles of Scientific Hell Perspectives on Psychological Science 7 (6) 643-644

This is based on a post from two years ago (far and away the most popular post I've ever done).

Now as historic achievements go, this is fairly niche, but I do think it's important.

Most of the problems with the way science works today are problems of communication. We're trying to do 21st century work with a 19th century publishing model, and the cracks are showing.

Academic papers are a fine way of presenting the final results of research - they're here to stay. But scientists ought to be communicating (with each other and with the public) in many other ways as well, and I think that anything we can do to break down the hegemony of the 'final paper' - whether it be blogging, arxiv, the Open Science Framework or raw data sharing - is a step forward.

In that regard, I think it's great that the boundaries between 'real' papers and alternative forms of scientific communication have just become a little blurrier.

The piece appears in a special issue of Perspectives on Psychological Science full to bursting with other papers that readers of this blog are likely to find interesting... and it's all free to access (at least for now).

Neuroskeptic (2012). The Nine Circles of Scientific Hell Perspectives on Psychological Science, 7 (6), 643-644 DOI: 10.1177/1745691612459519

John Bargh's "Transient and Ephemeral" Blogs

Leading social psychologist and Yale Professor John Bargh has been at the center of a number of controversies lately.

Most recently, researcher Brent Donnellan covered a case in which he was unable to replicate one of Bargh's experiments, which prompted Bargh to share his original raw data with him, but on the condition that he never discussed it publicly: What’s the First Rule about John Bargh’s Data? You do not talk about John Bargh’s data

But a couple of months back, even more sparks flew over an unrelated non-replication. Some other people didn't reproduce a different Bargh study.

In response to that non-replication, Bargh published two blog posts called "Nothing In Their Heads" and "Angry Birds", criticizing both the study itself and the journal it appeared in, PLoS ONE. It was a combative defence of his work.

However, Bargh seems to have since decided it was a bit too defensive, because the posts have been deleted. They just vanished: to my knowledge Bargh hasn't announced this, nor explained why.

Now interestingly enough, Bargh has just published a short paper in which he offers he thoughts on blogging - it's rather topical...

Debate among psychologists takes place formally in the published record of journal articles and books... this is the permanent record, as opposed to the relatively transient and ephemeral world of blogs.

As I understand (and use) them, blogs are like newspaper columns or spontaneous radio interviews, and meant to be a forum wherein one can provide the interested public with opinions, feelings, and conjectures; blogs are thus a potentially valuable outlet for ideas when used and evaluated appropriately...

[but they are] personal property whereas journal articles are public property
– as illustrated by one’s ability to edit, change, or delete one’s personal blog entries and one’s concomitant inability to do the same with published works (except to make necessary corrections with the consent of the journal editor).

Fair enough. However, the fact is, a public statement is a public statement. You can change your mind, but you can't change the past. In my book, to try to erase your past statements from the record is both deceptive - and counterproductive.

The internet never forgets... well, actually, I can't find copies of the deleted posts (Edit: See the comments, someone has saved them), so maybe it does, however there are dozens of references to them online, many highly critical. At best, what Bargh has achieved is that his critics are now the only sources for information about his work.

Bargh's new paper, by the way, is a response to this piece I blogged about about the question of free will.

Bargh, J. (2012). Social psychology cares about causal conscious thought, not free will per se British Journal of Social Psychology DOI: 10.1111/bjso.12011

Autism Brain Scans Flawed? You Read It Here First

According to a piece in Nature today, a major line of research about autism might be seriously flawed:

One of the most popular and widely accepted theories on the cause of autism spectrum disorders attributes the condition to disrupted connectivity between different regions of the brain.

This 'connectivity hypothesis' claims that the social and cognitive abnormalities in people with autism can be explained by a dearth of connections between distant regions of the brain. Some flavours of this theory also predict more connections between nearby brain regions.

Recent studies, however, have found that when a person moves their head while undergoing functional magnetic resonance imaging (fMRI) - a method that maps how different neuroanatomical structures of the brain interact in real time, its functional connectivity - it looks like the neural activity observed in autism. That's a sobering discovery...

So the characteristic pattern of "abnormal connectivity" in autism might not be real: it might just reflect the fact that people with autism move around more during the scan.

A sobering idea, indeed... but not an entirely new one. I suggested it over a year ago:

Head motion affects estimates of functional connectivity. The more motion, the weaker the measured connectivity in long-range networks, while shorter range connections were stronger... Disconcertingly, this is exactly what's been proposed to happen in autism (although in fairness, not all the evidence for this comes from fMRI). This clearly doesn't prove that the autism studies are all dodgy, but it's an issue. People with autism, and people with almost any mental or physical disorder, on average tend to move more than healthy controls.

Ben Deen, and Kevin Pelphrey (2012). Perspective: Brain scans need a rethink Nature

Recommend Me An Agent

I'm looking for a literary agent.

I have an idea for a book, it's non-fiction, about science, for a general audience. It'll cover some  themes I've written about on this blog, although it'll all be new material.

Anyway, if you can recommend any good agents who you think might be interested in this or if you are one and are interested - please let me know. You can email me at neuroskeptic at gmail dot com. I live in the UK, so a London-based agent would be ideal, but I'm open to all suggestions.

Naomi Wolf's "Vagina"

Naomi Wolf's "Vagina" is full of bad science about the brain - is an article I wrote for the New Statesman. It's about a new book which is... not very good.

I didn't come up with the title by the way, but I do rather like it.

See also the Neurocritic's take.

How To Lose Twitter Followers

Inspired by David Allen Green's How to lose followers on Twitter, I thought I'd share some tips on what to avoid doing if you want to be big on Twitter.

I don't think there's any simple formula for gaining followers. You just need to write "good" Tweets, where "good" is impossible to define and depends on what kind of thing you write about. However, there are some simple things that are pretty sure to lose you followers.

• Send a Tweet. Every time you Tweet, expect to lose followers. People will unfollow you when they see your Tweets and decide they don't want to hear more, and the more you post, the more likely they are to feel it's too much. Dense "bursts" of Tweets, in particular, may make people decide that you're taking up too much space in their time line. Tweeting is the only way to gain followers, but unless a Tweet actively gains followers, it will lose them.
• Treat Twitter as a social network. It's not. Or rather, it can be, and that's fine if you want to use it that way. But if you care about your follower count, then you're probably not thinking of it as one. Twitter is a microblogging platform, so treat your Tweets like blog posts aimed at your audience, rather than personal "chat" messages. Chat Tweets rarely gain followers... and that means they lose them (see above). It's not an absolute rule, and if you never chat, it will cut you off from important discussions. But chat should not be your default mode.
• Spam. There are various services that make cookie-cutter Tweets on your behalf. Usually they're a round up of your recent Tweets, or a follower count. In general, avoid these. Your followers want to hear from you, not from a robot, and they want to hear your thoughts, not your Twitter stats. They can be useful, but think very careful before using these.
• Be Bilingual. If you speak more than one language, that's awesome. It means you can communicate with more people. But don't try and mix languages on the same account. If half your Tweets are English and half are French, then half your Tweets are essentially just meaningless clutter, for any given follower. Make two accounts, one per language, and you'll get more followers overall.

On Twitter, It's Beer Before Liquor

People tweet about beer in the evenings, especially on Fridays, according to a not-very-surprising-but-still-fun little report in the journal Epidemiology: Using Twitter to Measure Behavior Patterns

The study used timeu.se, a free searchable database of millions of Tweets. The site grew out of an excellent bit of research you might remember from last year that examined how average mood varies over the course of the day and year.

People tweet about and presumably drink beer (and wine) most in the evenings, especially on Fridays and Saturdays. Smoking-related tweets however were mostly flat, although there did seem to be a small peak in the mornings.

So I ran a few searches of my own, and I noticed that different drinks peak at different times. "Beer" is most popular in the early evening, closely followed by "Wine", but "Vodka" doesn't max out until midnight.

Looks like people are not following the old "beer before liquor, never sicker" rule.

Also, while wine gets the most tweets during the week, beer and vodka really take off at the weekend.

 Cunningham A. John (2012). Using Twitter to Measure Behavior Patterns Epidemiology DOI: 10.1097/EDE.0b013e3182625e5d

Love Truth? Wait.

Britain may be hosting the Olympics, but that hasn't stopped us indulging in our own national sport of complaining. Many of the complaints in the past 24 hours or so have been about this chap:

Rileyy_69 attacked a celebrity on Twitter, who called him out on it, rileyy_69 attacked him more, thousands of fans of said celebrity attacked him, he attacked some of them back, then he apologized, but then attacked again, and eventually someone reported him to the police, and he was arrested on Tuesday morning for malicious communications or something.

All very exciting, but so what?

Should we pity this guy, or did it he bring it on himself? Were the thousands who attacked him jumping on the bandwagon, or justifiably outraged? Should he have been arrested, and if not, why? Because the law in question ought to be repealed, or because it's a fine law but was wrongly applied in this case?

Good questions. We don't know enough yet to answer them. We don't know this person, his life story, his mental health situation, etc. Some details have now started to emerge, but generally the early, fragmentary reports in cases like this only add to the confusion.

It's too early to tell. I don't think anyone can dispute this. Unless you i) know Rileyy69 in real life and ii) are an expert in the relevant areas of law and iii) have read all his Tweets, not just the ones that made it into the newspapers, you are probably not in a position to judge.

It's too early to say, but that's never stopped anyone.

Newspapers and blogs are full of definitive, final judgements on these questions. Both those broadly in favor of the arrest of Rileyy_69, and those opposed, are equally premature. If there is a difference, it's that the latter group also include hypocrites, who swiftly took to Twitter to criticize the knee jerk mob mentality of the Twitterati.

One who really cared about Rileyy_69, the law, the media, or whatever else they claimed to, would above all want to establish the facts before commenting. The truth will out; we can but wait, or try to help it along. But we should not try to outrun it.

The truth is slow.

And that's fine. There's rarely, and certainly not in this case, a need to form your opinions within minutes and to nail your theses to the door of the cathedral within a day of the event. Just wait! You'll be in good company; few of the great minds of history measured time in hours.

"Ah", you might say, "but those who attacked Rileyy_69 on Twitter were, themselves, doing what you're criticizing!". They were, actually, but that's what Twitter is for. Tweets are about speed and in its place, that's fine. The human brain responds to stimuli within about 100 milliseconds; you give people the chance to type that response, and they will. To criticize that is to criticize human nature.

No, the problem is not those who use an avowedly instant communication service as intended. It's those who try to export that mode of thought into the ancient and higher medium of prose longer than 140 characters.

For everything there is a time, a time to Tweet and a time to think. Just don't mix them up.

Why Blogs Fail

I can think of several new neuroscience blogs that started out with some really nice content, but then they disappeared after a few weeks or months. I'm sure the same must be true of other genres. This is a shame.

Thinking back over the early days of Neuroskeptic, my advice to new bloggers is: it gets better. The early days of any blog are psychologically tough because almost inevitably, your first posts are not going to get the recognition they deserve.

That's because people tend to really pour their hearts into early posts - these are the ones that express thoughts you've been mulling over for ages and are finally writing about - and then inevitably, hardly anyone reads them, because it's a new blog and no-one even knows it's there yet. Certainly that was my experience.

Luckily, it doesn't stay that way. Your first posts will flop, at least in relation to your own expectations, but remember that a) it's nothing personal and b) no-one except you cares. Only you can see your traffic stats and whatever, but even if everyone knew them, they wouldn't mind. You need to push on through that stage and once you do, you won't care about it either.

To get past the first stage, you need to "sell" your blog. I think a lot of new bloggers forget this, or think it somehow won't apply to them, which sets them up for disappointment. Of course, good content is essential - no matter how hard you try, you can't sell crap. But great writing alone is not enough. No, not even yours.

Promotion is part of blogging, but once you get into the right mindset, you'll realize that it's not a chore so much as a natural extension of writing. You write something, and then you go and find people who'll be interested in it, and who might have interesting comments about it, and try and get them involved. Or you get involved in conversations about the topics you're interested in.

Sell, don't beg. Outright asking more established people for links, retweets etc. rarely works and it looks bad. Get people interested in it. If that's a chore, then it means you're not really interested in your own stuff, in which case that's a problem.

If you've done this for, say, a year, then I'd say you've given blogging a good shot and you can make an informed decision as to whether or not it's for you. But if you quit after just a couple of months because "I tried blogging and it didn't work out" or "I had a blog but no-one read it" then I'd say you're probably making a mistake. You haven't experienced all of blogging, only the start of it, which is the toughest and least rewarding part. It gets better.

Big Pharma Read Neuroskeptic?

A few weeks back I blogged about an error-ridden paper from pharmaceutical company Janssen. It  reported on the failure of a candidate antidepressant, JNJ-18038683. But it was rubbish: the Abstract contradicted the results of the study, wrongly claiming that the drug did statistically significantly better than placebo in a particular analysis, when it didn't. And they repeatedly mixed up the names of two other antidepressants.

I posted on May 17th. On May 23rd, a new version of the offending article quietly appeared on the journal's website: here it is. But the old version is still up, although I'm not sure it's intended to be, because the link is gone, so I think the only way to find it is from this blog.

Interestingly, the new manuscript corrects those two issues I noted. As far as I can see those are the only changes. Coincidence?

The original paper was a "Fast Forward" online accelerated publication manuscript, and it's common for these to be corrected in minor ways when they're officially published (i.e. when they appear in print), but that's not what happened here, because the new version is still a Fast Forward. This kind of revision is unusual.

So it seems that someone at Janssen is reading this blog!

If so: Hey. Believe it or not, I'm on your side, I want you to succeed. I suffer from depression, and I've love it if you came up with an actually good new antidepressant. But your industry hasn't released one in at least 10 years (be honest), and you're not fooling anyone with clever statistical tricks.

Forget that, and invest in some proper science. For example, ketamine is clearly the most exciting potential antidepressant right now, and glutamate could be the next serotonin. But because no-one has tested it against an active placebo, no-one, including you, knows whether it's really working. Run a really serious trial of ketamine, if it does work, then that's your next generation of antidepressants right there. If not, better to know that now than later when you've sunk billions into the idea.

Bipolar Disorder - A BRIDGE to nowhere?

Last August I blogged about a research paper that claimed that almost half of all people suffering from depression actually have features of bipolar disorder - including me: So Apparantly I'm Bipolar

It was called the BRIDGE study. I took issue with it for various reasons, including the fact that it counted as 'bipolar features' any periods of irritable or elevated mood, even if they were associated with drug treatment:

Under the new regime if you've ever been irritable, high, agitated or hyperactive, on antidepressants or not, you meet "Bipolar Specifier" criteria, so long as it was marked enough that someone else noticed it...

A cynic would say that this is a breathtaking piece of psychiatric marketing. You give people antidepressants, then you diagnose them with bipolar on the basis of their reaction to those drugs, thus justifying selling them yet more drugs.

The cynic would not be surprised to learn that this study was sponsored by pharmaceutical company Sanofi. 

Now a crack team of psychiatrists have written a Letter to the Editor criticizing BRIDGE and they say... pretty much what I said: BRIDGE Study Warrants Critique. They do make a couple of new points also.

The 8 authors of the Letter include David Allen, David Healy, Peter Parry and Jon Jureidini, all major critical voices in psychiatry. However... while this A-Team make an excellent case that BRIDGE is a step in the direction of overdiagnosis and overtreatment of bipolar, they drop the ball slightly when they say:

The article concluded with an appeal to use “mood stabilizers,” presumably atypical antipsychotics, which are less efficacious than lithium. The sponsor has a medication in this class.

Sanofi does make the atypical antipsychotic amisulpiride, but it's not generally referred to as a "mood stabilizer", and I'm not sure why you'd assume that Sanofi had amisulpiride specifically in mind. The BRIDGE team exploit this in their rebuttal letter:

Allen et al cast unseemly aspersions that the BRIDGE study was a vehicle to promote sales of an antipsychotic drug sold by sanofi-aventis. sanofi-aventis has no antipsychotic with an indication for bipolar disorder. We know of no evidence that this was the case at any stage of development and execution of the BRIDGE study.

Maybe so, but as I said in my post, Sanofi also make some popular brands of valproate/valproic acid, a prototypical "mood stabilizer" which is widely used in bipolar disorder. I'd have said that was the more likely candidate...

Fundamentally, we know that Sanofi "was involved in the study design, conduct, monitoring, data analysis, and preparation of the report." We also know that Sanofi is exists to make profit by selling drugs. So either Sanofi thought that this study would make them a profit eventually, by selling more drugs... or they threw money and time at this for no commercial reason. Hmm.

The reply concludes with the frankly bizarre statement that:

Allen et al view their position as part of a “debate” about the “ever-widening bipolar spectrum.” We consider data, not debates, as central to the progress in the scientific understanding of mood disorders...

But science is a debate about data. Data by themselves are just numbers; to be useful, they must be interpreted, and scientific debates aim at arriving at such interpretations. No-one is questioning the BRIDGE data as such, we're questioning what it means.

David M. Allen, et al (2012). BRIDGE Study Warrants Critique Archives of General Psychiatry, 69 (6) DOI: 10.1001/archgenpsychiatry.2012.118

Why We Sleep, Revisted

I've got another guest post over at Discover magazine: Is the Purpose of Sleep to Let Our Brains “Defragment,” Like a Hard Drive?

It's an expanded version of two Neuroskeptic posts(1,2) about the theory that the job of slow-wave sleep is to prune connections in the brain, connections which tend to become stronger while we're awake and might become too strong without periodic resetting.

One of the commenters on the Discover post pointed out that this idea a bit like a much older idea about sleep, from Francis Crick (of discovering-the-structure-of-DNA fame). Back in 1983, Crick and Graeme Mitchison proposed that dreaming sleep serves to help us "unlearn": The Function of Dream Sleep
Their idea was a bit different, but it was really very elegant.

The sleeping brain, they said, is cut off from real sensory input, and is subject only to essentially random activity variations. However, sometimes these meaningless inputs may be 'interpreted' as having meaning, activating representations (concepts, thoughts, memories) that we've learned to recognize when awake.

These "patterns" that the brain wrongly "sees" in noise are what we experience as dreams. Crick and Mitchison's point is that, ideally, a pattern recognition system (like the brain) shouldn't be picking up patterns from random noise because that would be a sign that it was biased in favor of those patterns - "obsessed" with them, as it were, and liable to see them everywhere. So it would be good if there were some way of identifying the brain's overlearned biases and (partially) unlearning them.

That's what dreams do, somehow, according to Crick. It's like if dreams are a self-administered Rorschach test that the brain uses to work out what's "weighing on its mind"! Incidentally, this is an idea I once suggested (much less clearly) myself.

It's a beautiful and ingenious theory, although as the authors admitted, it would be very hard to test and it leaves wide open the question of how dreams could cause memories to be "unlearned" or indeed whether unlearning is even possible in the brain. It's also not very similar to the modern "defrag" theory, because Crick was talking about the dreaming rapid eye movement stage of sleep, not slow-wave sleep.

Francis Crick and Graeme Mitchison (1983). The Function of Dream Sleep Nature, 304, 111-114