Tuesday, August 17, 2010

What The Internet Thinks About Antidepressants

Toronto team Rizo et al offer a novel approach to psychopharmacology: trawling the internet for people's opinions. It's a rapid, web-based method for obtaining patient views on effects and side-effects of antidepressants.

They designed a script to Google the names of several antidepressants in the context of someone who's taking them, and checks to see if they describe any side-effects.
A large number of URLs were rapidly screened through Google Search™, using one server situated in Ohio, USA. The search strategy used language strings to denote active antidepressant drug usage, such as “I'm on [name of antidepressant]…” or “I
have been on [antidepressant] for ….”, or “I've started [antidepressant]…”, or “the [antidepressant] is giving me or causing me…”
They then used a thing called OpenCalais™ to read the search hits and decide whether they were mentioning particular diseases or symptoms. OpenCalais is a natural language processor which is meant to be able to automatically extract the meaning from text. However, to make sure it wasn't doing anything silly (natural language processing is quite tricky), they manually checked the results.

What happened? They found about 5,000 hits in total from people taking antidepressants, ranging from 210 for mirtazapine (Remeron) up to 835 for duloxetine (Cymbalta). That doesn't seem like all that many considering they searched on the entire internet, although they only searched English language websites.

Anyway, drowsiness, sleepiness or tiredness was mentioned in from 6.4% (duloxetine) down to 2.9% (fluoxetine) of the hits. Insomnia was noted in 4% (desvenlafaxine) down to 2.2% fluoxetine. And so on.

These results are a lot lower than anything previously reported from clinical trials, where the prevalence of drowsiness, for example, is often around 25% (vs. 10% on placebo); with some drugs, it's higher. So there's a big discrepancy, and it's hard to interpret these results. Maybe lots of people are having side effects and just not bothering to write about them. Or they're too embarrassed. Etc.

Still, it's a very clever idea it would probably be better used trying to discover which drugs work best. Neuroskeptic readers will know that clinical trials of antidepressants are flawed in several ways. I'd say they're actually better at telling us about side effects (which are probably roughly the same in clinical trials and in real life) than they are at telling us about efficacy (where this assumption doesn't hold)...

Links: There are many websites where people describe their experiences of medical treatments ranging from the fancy to the crude (but much more informative)...

ResearchBlogging.orgRizo C, Deshpande A, Ing A, & Seeman N (2010). A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants. Journal of affective disorders PMID: 20705344

What The Internet Thinks About Antidepressants

Toronto team Rizo et al offer a novel approach to psychopharmacology: trawling the internet for people's opinions. It's a rapid, web-based method for obtaining patient views on effects and side-effects of antidepressants.

They designed a script to Google the names of several antidepressants in the context of someone who's taking them, and checks to see if they describe any side-effects.
A large number of URLs were rapidly screened through Google Search™, using one server situated in Ohio, USA. The search strategy used language strings to denote active antidepressant drug usage, such as “I'm on [name of antidepressant]…” or “I
have been on [antidepressant] for ….”, or “I've started [antidepressant]…”, or “the [antidepressant] is giving me or causing me…”
They then used a thing called OpenCalais™ to read the search hits and decide whether they were mentioning particular diseases or symptoms. OpenCalais is a natural language processor which is meant to be able to automatically extract the meaning from text. However, to make sure it wasn't doing anything silly (natural language processing is quite tricky), they manually checked the results.

What happened? They found about 5,000 hits in total from people taking antidepressants, ranging from 210 for mirtazapine (Remeron) up to 835 for duloxetine (Cymbalta). That doesn't seem like all that many considering they searched on the entire internet, although they only searched English language websites.

Anyway, drowsiness, sleepiness or tiredness was mentioned in from 6.4% (duloxetine) down to 2.9% (fluoxetine) of the hits. Insomnia was noted in 4% (desvenlafaxine) down to 2.2% fluoxetine. And so on.

These results are a lot lower than anything previously reported from clinical trials, where the prevalence of drowsiness, for example, is often around 25% (vs. 10% on placebo); with some drugs, it's higher. So there's a big discrepancy, and it's hard to interpret these results. Maybe lots of people are having side effects and just not bothering to write about them. Or they're too embarrassed. Etc.

Still, it's a very clever idea it would probably be better used trying to discover which drugs work best. Neuroskeptic readers will know that clinical trials of antidepressants are flawed in several ways. I'd say they're actually better at telling us about side effects (which are probably roughly the same in clinical trials and in real life) than they are at telling us about efficacy (where this assumption doesn't hold)...

Links: There are many websites where people describe their experiences of medical treatments ranging from the fancy to the crude (but much more informative)...

ResearchBlogging.orgRizo C, Deshpande A, Ing A, & Seeman N (2010). A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants. Journal of affective disorders PMID: 20705344

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Monday, August 16, 2010

BOM DIA!!!!!!

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Sunday, August 15, 2010

Is Your Brain Autistic?

There's been a lot of buzz and some scepticism about the
New brain scan to diagnose autism
Here's a quick overview. Autism is believed to be a disorder of brain development. If so, it should be possible to diagnose it based on a brain scan. Unfortunately, it's not. You can't tell, from a scan, whether someone has autism or not. Not even if you're a world expert.

There are reports of various differences between autistic and non-autistic brains - a bit smaller here, a bit bigger there - but there's a lot of overlap. So at present, diagnosis of autism is purely based on symptoms.

Ecker et al, a team based at the Institute of Psychiatry in South London, made use of a mathematical technique called a Support Vector Machine (SVM) to try to spot differences that the naked eye can't. An SVM is a learning algorithm: you "teach" it to spot differences by showing it lots of examples. In this case, they showed it 20 autistic brains, and the brains of 20 healthy controls matched for age, gender, and IQ.

How does an SVM work? Imagine that there are two kinds of, say, fruit. Both are kind of round but A's are more spherical than B's. So you could draw a plot of sphere-ness, and find a line separating A and B:
An SVM is an automatic method of finding that line. How? It's complex, but fortunately you don't need to know (I don't). Of course, that's easy, but imagine that things got more tricky. As well as the variable of roundness, there's colour. Fruit B can be either spherical and dark, or non-spherical and light (maybe it's two different stages of ripeness).

An SVM could do this easily too:
Now suppose that there's 1000 different variables, and you want to find the "line" - actually a 1000-dimensional "hyperplane" (a line is 2D, a plane is 3D, anything with 4D or more is a hyper-plane) - dividing the "space" of possibilities into two.

For a human that's impossible, but not for an SVM. This is essentially what Ecker et al did. Each dimension of their "space" was the amount of grey matter at a particular point in the brain. So, they were training the SVM to distinguish between autistic brains and non-autistic brains, based on their shape, but in a much more complex way than a human could.

Did it work? Surprisingly well. Here's the end result (the multi-dimensional space has been helpfully compressed into 2D by the SVM):
It wasn't perfect, but the best approach, based on the cortical thickness in the left hemisphere, managed 90% accuracy, which is pretty awesome. Focussing on the headline 90% result is cherry-picking a bit, because using other variables, like cortical curvature, wasn't as good, but even the worst ones managed 70-85%, much better than chance (50%). Importantly, they also tried the system on 20 adults with ADHD, and it classified them as non-autistic. This shows that it's not just measuring "normality".

*

Now the question everyone's asking: is this going to be used for diagnosis in the real world any time soon? The first thing to remember is that this is a scientific paper, and this result is first and foremost of research interest: it provides clues towards the biology, and ultimately the causes, of autism.

But let's suppose you're a clinician and you have someone who you suspect may have autism, but you're not sure. They're a tricky one, a borderline case. You use this system on their brain and it says they are autistic. Should that factor into your decision? It depends. The fact is that rather than an either-or result, the SVM returns a distance from the hyperplane for each brain. You can see this clearly in the plot above.

In my opinion, if you have a borderline case, and the machine says he's borderline, then that's not much help, and it doesn't matter if he's just over the line, or not quite over it. You already knew he was borderline.

But if the machine says that he's deep into the autism space, then I think that is something. It tells you that his brain is very typical of people with autism. Interestingly, Ecker et al found that distance from the hyperplane correlated with symptom severity for "social" and "communication" symptoms (though not "repetitive behaviours"). That's a pretty cool result because the SVM wasn't trained to do that, it was trained to decide on an either-or basis.

What needs to happen next? As it stands, this system only works for adults: it would fail for children or teenagers, because their brains are a very different size and shape. Exactly the same SVM approach could be used in younger age groups, though, so long as the patients and the controls were the same age.

We also need to make sure that the SVM can tell the difference between autism and other conditions; Ecker et al showed that it could distinguish autism from ADHD, but that's only one comparison and it might not be the hardest one: I would want to see it tested against things like epilepsy, mental retardation, and dyslexia as well.

Overall though, this is very exciting work, and certainly a cut above most "Brain Scans To Diagnose Mental Illness" studies that make it into the headlines.

Full Discloser: I know some of the researchers involved in this work.

Links: The same team had a paper out a few months back, using a slightly less sophisticated SVM approach, which managed 80% accuracy. I wrote about another application of SVMs previously: How To Read Minds. This study has been blogged about at The New Republic and Dormivigilia
.

ResearchBlogging.orgEcker C, Marquand A, Mourão-Miranda J, Johnston P, Daly EM, Brammer MJ, Maltezos S, Murphy CM, Robertson D, Williams SC, & Murphy DG (2010). Describing the brain in autism in five dimensions--magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. Journal of Neuroscience, 30 (32), 10612-23 PMID: 20702694

Is Your Brain Autistic?

There's been a lot of buzz and some scepticism about the
New brain scan to diagnose autism
Here's a quick overview. Autism is believed to be a disorder of brain development. If so, it should be possible to diagnose it based on a brain scan. Unfortunately, it's not. You can't tell, from a scan, whether someone has autism or not. Not even if you're a world expert.

There are reports of various differences between autistic and non-autistic brains - a bit smaller here, a bit bigger there - but there's a lot of overlap. So at present, diagnosis of autism is purely based on symptoms.

Ecker et al, a team based at the Institute of Psychiatry in South London, made use of a mathematical technique called a Support Vector Machine (SVM) to try to spot differences that the naked eye can't. An SVM is a learning algorithm: you "teach" it to spot differences by showing it lots of examples. In this case, they showed it 20 autistic brains, and the brains of 20 healthy controls matched for age, gender, and IQ.

How does an SVM work? Imagine that there are two kinds of, say, fruit. Both are kind of round but A's are more spherical than B's. So you could draw a plot of sphere-ness, and find a line separating A and B:
An SVM is an automatic method of finding that line. How? It's complex, but fortunately you don't need to know (I don't). Of course, that's easy, but imagine that things got more tricky. As well as the variable of roundness, there's colour. Fruit B can be either spherical and dark, or non-spherical and light (maybe it's two different stages of ripeness).

An SVM could do this easily too:
Now suppose that there's 1000 different variables, and you want to find the "line" - actually a 1000-dimensional "hyperplane" (a line is 2D, a plane is 3D, anything with 4D or more is a hyper-plane) - dividing the "space" of possibilities into two.

For a human that's impossible, but not for an SVM. This is essentially what Ecker et al did. Each dimension of their "space" was the amount of grey matter at a particular point in the brain. So, they were training the SVM to distinguish between autistic brains and non-autistic brains, based on their shape, but in a much more complex way than a human could.

Did it work? Surprisingly well. Here's the end result (the multi-dimensional space has been helpfully compressed into 2D by the SVM):
It wasn't perfect, but the best approach, based on the cortical thickness in the left hemisphere, managed 90% accuracy, which is pretty awesome. Focussing on the headline 90% result is cherry-picking a bit, because using other variables, like cortical curvature, wasn't as good, but even the worst ones managed 70-85%, much better than chance (50%). Importantly, they also tried the system on 20 adults with ADHD, and it classified them as non-autistic. This shows that it's not just measuring "normality".

*

Now the question everyone's asking: is this going to be used for diagnosis in the real world any time soon? The first thing to remember is that this is a scientific paper, and this result is first and foremost of research interest: it provides clues towards the biology, and ultimately the causes, of autism.

But let's suppose you're a clinician and you have someone who you suspect may have autism, but you're not sure. They're a tricky one, a borderline case. You use this system on their brain and it says they are autistic. Should that factor into your decision? It depends. The fact is that rather than an either-or result, the SVM returns a distance from the hyperplane for each brain. You can see this clearly in the plot above.

In my opinion, if you have a borderline case, and the machine says he's borderline, then that's not much help, and it doesn't matter if he's just over the line, or not quite over it. You already knew he was borderline.

But if the machine says that he's deep into the autism space, then I think that is something. It tells you that his brain is very typical of people with autism. Interestingly, Ecker et al found that distance from the hyperplane correlated with symptom severity for "social" and "communication" symptoms (though not "repetitive behaviours"). That's a pretty cool result because the SVM wasn't trained to do that, it was trained to decide on an either-or basis.

What needs to happen next? As it stands, this system only works for adults: it would fail for children or teenagers, because their brains are a very different size and shape. Exactly the same SVM approach could be used in younger age groups, though, so long as the patients and the controls were the same age.

We also need to make sure that the SVM can tell the difference between autism and other conditions; Ecker et al showed that it could distinguish autism from ADHD, but that's only one comparison and it might not be the hardest one: I would want to see it tested against things like epilepsy, mental retardation, and dyslexia as well.

Overall though, this is very exciting work, and certainly a cut above most "Brain Scans To Diagnose Mental Illness" studies that make it into the headlines.

Full Discloser: I know some of the researchers involved in this work.

Links: The same team had a paper out a few months back, using a slightly less sophisticated SVM approach, which managed 80% accuracy. I wrote about another application of SVMs previously: How To Read Minds. This study has been blogged about at The New Republic and Dormivigilia
.

ResearchBlogging.orgEcker C, Marquand A, Mourão-Miranda J, Johnston P, Daly EM, Brammer MJ, Maltezos S, Murphy CM, Robertson D, Williams SC, & Murphy DG (2010). Describing the brain in autism in five dimensions--magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. Journal of Neuroscience, 30 (32), 10612-23 PMID: 20702694

Thursday, August 12, 2010

Drugs for Starcraft Addiction

Are you addicted to Starcraft? Do you want to get off Battle.net and on a psychoactive drug?

Well, South Korean psychiatrists Han et al report that Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

They took 11 people with "Internet Game Addiction" - the game being Starcraft, this being South Korea - and gave them the drug bupropion (Wellbutrin), an antidepressant that's also used in drug addiction and smoking cessation. These guys (because, predictably, they were all guys) were seriously hooked, playing on average at least 4 hours per day.
Six were absent from school because of playing Internet video game in Internet cafes for more than 2 months. Two IAGs had been divorced because of excessive Internet use at night.
They helpfully summarize Starcraft for the layperson:
As a military leader for one of three species, players must gather resources for training and expanding their species’ forces. Utilizing various strategies and alliances with other species, players attempt to lead their own species to victory.
Which is all true, but it doesn't quite communicate the sheer obsessiveness that's require to win this game. As Penny Arcade said "it is OCD masquerading as recreation", and that's coming from someone who literally plays video games for a living.

Anyway, apparently the drug worked:
After 6 weeks of bupropion SR treatment in the IAG group, there were significant decreases in terms of craving for playing StarCraft (23.6%), total playing game time (35.4%), and Internet Addiction Scale scores (15.4%)
They also did some fMRI and found that the addict's brains responded more strongly to pictures of Zerglings than did control people, and that the drug reduced activity a bit. But there was no placebo group, so we have no idea whether this was the drug or not.

Sadly, the point is moot, because Starcraft II has just come out, and it's more addictive than ever. I'm off to try and optimize my Terran build order, and by God I will get those 10 marines out in the first 5 minutes if it takes me all night...

ResearchBlogging.orgHan DH, Hwang JW, & Renshaw PF (2010). Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction. Experimental and clinical psychopharmacology, 18 (4), 297-304 PMID: 20695685