Prozac Made My Cells Spiky

A great many neuroscientists are interested in clinical depression and antidepressants. We're still a long way from understanding depression on a biological level - and if anyone tries to tell you otherwise, they're probably trying to sell you something. I've previously discussed the controversies surrounding the neurotransmitter serotonin - according to popular belief, the brain's "happy chemical". My conclusion was that although clinical depression is not caused by "low serotonin" alone, serotonin does play an important role in mood at least in some people.

A paper published recently in Molecular Psychiatry makes a number of important contributions to the literature on depression and antidepressants; I haven't seen it discussed elsewhere, so here is make take on it. The paper is by a Portuguese research group, Bessa et. al., and it's titled The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. The findings are right there in the title, but a little history is required in order to appreciate their significance.

For a long time, the only biological theory which attempted to explain clinical depression and how antidepressants counteract it was the monoamine hypothesis. During the early 1960s, it was noticed that early antidepressant drugs, such as imipramine, all inhibited either the breakdown or the removal (reuptake) of chemicals in the brain called monoamines, including serotonin. This led many to conclude that antidepressants improve mood by raising monoamine levels, and that depression is probably caused by some kind of monoamine deficiency. For various reasons (not all of them good ones), it was later decided that serotonin was the crucial monoamine involved in mood, although for several years another, noradrenaline, was favored by most people.

This "monoamine hypothesis" was always a little shaky, and over the past decade or so, an alternative approach has become increasingly fashionable. If you were so inclined, you might even call it a new paradigm. This is the proposal that antidepressants work by promoting the survival and proliferation of new neurones in certain areas of the brain - the "neurogenesis hypothesis". Neurogenesis, the birth of new cells from stem cells, occurs in a couple of very specific regions of the adult brain, including the elaborately named subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Many experiments on animals have shown that chronic stress, and injections of the "stress hormone" corticosterone, can suppress neurogenesis, while a wide range of antidepressants block this effect of stress and promote neurogenesis. (Other evidence shows that antidepressants probably do this by inducing the expression of neurotrophic signaling proteins, like BDNF.)

The literature on stress, neurogenesis, and antidepressants, is impressive and growing rapidly. For good reviews, see Duman (2004) and Duman & Monteggia (2006). However, the crucial question - do antidepressants work by boosting hippocampal neurogenesis? - remains a controversial one. The hippocampus is not an area generally thought of as being involved in mood or emotion, and damage to the human hippocampus causes amnesia, not depression. Given that the purpose (if any) of adult neurogenesis remains a mystery, it's entirely possible that neurogenesis has nothing to do with depression and mood.

To establish whether neurogenesis is involved in antidepressant action, you need to to manipulate it - for example, by blocking neurogenesis and seeing if this makes antidepressants ineffective. This is practically quite tricky, but Luca Santarelli et. al. (2003) managed to do it by irradiating the hippocampi of mice with x-rays. They found that this made two antidepressants (fluoxetine, aka Prozac, and imipramine) ineffective in protecting the animals against the detrimental effects of chronic stress. This was a landmark result, and raised a lot of interest in the neurogenesis theory.

This new paper, however, says differently. The authors gave lab rats a six-week Chronic Mild Stress treatment, a Guantanamo Bay-style program of intermittent food deprivation, sleep disruption, and confinement. Chronic stress has various effects on rats, including increased anxiety and decreased time spent grooming leading to fur deterioration. These behaviours and others can be quantified, and are treated as a rat analogue of human clinical depression - whether this is valid is obviously debatable, but I'm willing to accept it at least until a better animal model comes along.

Anyway, some of the rats were injected with antidepressants during the final two weeks of the stress procedure. As expected, these rats coped better with the stress at the end of six weeks. This graph shows the effects of stress and antidepressants on the rat's behaviour in the Forced Swim (Porsolt) Test. Higher bars indicate more "depressed" behaviour. The second pair of bars, representing the stressed rats who got placebo injections, is a lot higher than the first pair of bars representing rats who were not subjected to any stress. In other words, stress made rats "depressed" - no surprise. The other four pairs of bars are pretty much the same height as the first pair; these are rats who got antidepressants, showing that they were resistant to the effects of stress.

The crucial finding is that the white and the black bars are all pretty much the same height. The black bars represent animals who were given injections of methylazoxymethanol (MAM), a cytostatic toxin which blocks cell division (rather like cancer chemotherapy). As you can see, MAM had no effect at all on behaviour in the swim test. It had no effect on most other tests, although it did seem to make the rats more anxious in one experiment.

However, MAM powerfully inhibited neurogenesis. This second graph shows the number of hippocampal cells expressing KI-67, a protein which is a marker of neuroproliferation. As expected, stress reduced neurogenesis and antidepressants increased it. MAM (black bars again) reduced neurogenesis, and in particular, it completely blocked the ability of antidepressants to increase it.

But as we saw earlier, MAM did not stop antidepressants from protecting rats against stress. So, the authors concluded, neurogenesis is not necessary for antidepressants to work. This contradicts the landmark finding of Santarelli et. al. - why the discrepency? There are so many differences between the two experiments that there could be any number of explanations - the current study used rats, while Santarelli used mice, for one thing, and that could well be important. Whatever the reason, this result suggests at the least that neurogenesis is not the only mechanism by which antidepressants counteract the effects of stress in animals.

The most interesting aspect of this paper, to my mind, was an essentially unrelated new finding. Stress was found to reduce the volume of several areas of the rat's brain, including the hippocampus and also the medial prefrontal cortex (mPFC). Unlike the hippocampus, this is an area known to be involved in motivation and emotion. Importantly, the authors found that following stress, the mPFC did not shrink because neurones were dying or because fewer neurones were being born, but rather because the existing neurones were changing shape - stress caused atrophy of the dendritic spines which branch out from neurones. Dendrites are essential for communication between neurones.

As you can see in the drawings above, stress (the middle column) caused shrinking and stunting of the dendrites in pyrimidal neurones from three areas relative to the unstressed rats (left), while those rats recieving antidepressants as well as stress showed no such effect (right). The cytostatic MAM had no effect whatsoever on dendrites. Further work found that antidepressants increase expression of NCAM1, a protein which is involved in dendritic growth.

So what does this mean? Well, for one thing, it doesn't prove that antidepressants work by increasing dendritic branching. Cheekily, the authors come close to implying this in their choice of title for the paper, but the published evidence shows no direct evidence for this. To find out, you would have to show that blocking the effects of antidepressants on dendrites also blocks their beneficial effects. I suspect this is what the authors are now working hard to try to do, but they haven't done so yet.

It also doesn't mean that taking Prozac will change the shape of your brain cells. It might well do, but this was a study in rats given huge doses of antidepressants (by human standards), so we really don't know whether the findings apply to humans. On the other hand, if Prozac changes the shape of your cells, this study suggests that stressful situations do too - and Prozac, if anything, will put your cells back to "normal".

Finally, I don't want to suggest that the neurogenesis theory of depression is now "dead". In neuroscience, theories never live or die on the basis of single experiments (unlike in physics). But it does suggest that the much-blogged-about neurogenesis hypothesis is not the whole story. Depression isn't just a case of too little serotonin, and it isn't just a case of too little neurogenesis or too little BDNF either.


J M Bessa, D Ferreira, I Melo, F Marques, J J Cerqueira, J A Palha, O F X Almeida, N Sousa (2008). The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling Molecular Psychiatry DOI: 10.1038/mp.2008.119

Prozac Made My Cells Spiky

A great many neuroscientists are interested in clinical depression and antidepressants. We're still a long way from understanding depression on a biological level - and if anyone tries to tell you otherwise, they're probably trying to sell you something. I've previously discussed the controversies surrounding the neurotransmitter serotonin - according to popular belief, the brain's "happy chemical". My conclusion was that although clinical depression is not caused by "low serotonin" alone, serotonin does play an important role in mood at least in some people.

A paper published recently in Molecular Psychiatry makes a number of important contributions to the literature on depression and antidepressants; I haven't seen it discussed elsewhere, so here is make take on it. The paper is by a Portuguese research group, Bessa et. al., and it's titled The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. The findings are right there in the title, but a little history is required in order to appreciate their significance.

For a long time, the only biological theory which attempted to explain clinical depression and how antidepressants counteract it was the monoamine hypothesis. During the early 1960s, it was noticed that early antidepressant drugs, such as imipramine, all inhibited either the breakdown or the removal (reuptake) of chemicals in the brain called monoamines, including serotonin. This led many to conclude that antidepressants improve mood by raising monoamine levels, and that depression is probably caused by some kind of monoamine deficiency. For various reasons (not all of them good ones), it was later decided that serotonin was the crucial monoamine involved in mood, although for several years another, noradrenaline, was favored by most people.

This "monoamine hypothesis" was always a little shaky, and over the past decade or so, an alternative approach has become increasingly fashionable. If you were so inclined, you might even call it a new paradigm. This is the proposal that antidepressants work by promoting the survival and proliferation of new neurones in certain areas of the brain - the "neurogenesis hypothesis". Neurogenesis, the birth of new cells from stem cells, occurs in a couple of very specific regions of the adult brain, including the elaborately named subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Many experiments on animals have shown that chronic stress, and injections of the "stress hormone" corticosterone, can suppress neurogenesis, while a wide range of antidepressants block this effect of stress and promote neurogenesis. (Other evidence shows that antidepressants probably do this by inducing the expression of neurotrophic signaling proteins, like BDNF.)

The literature on stress, neurogenesis, and antidepressants, is impressive and growing rapidly. For good reviews, see Duman (2004) and Duman & Monteggia (2006). However, the crucial question - do antidepressants work by boosting hippocampal neurogenesis? - remains a controversial one. The hippocampus is not an area generally thought of as being involved in mood or emotion, and damage to the human hippocampus causes amnesia, not depression. Given that the purpose (if any) of adult neurogenesis remains a mystery, it's entirely possible that neurogenesis has nothing to do with depression and mood.

To establish whether neurogenesis is involved in antidepressant action, you need to to manipulate it - for example, by blocking neurogenesis and seeing if this makes antidepressants ineffective. This is practically quite tricky, but Luca Santarelli et. al. (2003) managed to do it by irradiating the hippocampi of mice with x-rays. They found that this made two antidepressants (fluoxetine, aka Prozac, and imipramine) ineffective in protecting the animals against the detrimental effects of chronic stress. This was a landmark result, and raised a lot of interest in the neurogenesis theory.

This new paper, however, says differently. The authors gave lab rats a six-week Chronic Mild Stress treatment, a Guantanamo Bay-style program of intermittent food deprivation, sleep disruption, and confinement. Chronic stress has various effects on rats, including increased anxiety and decreased time spent grooming leading to fur deterioration. These behaviours and others can be quantified, and are treated as a rat analogue of human clinical depression - whether this is valid is obviously debatable, but I'm willing to accept it at least until a better animal model comes along.

Anyway, some of the rats were injected with antidepressants during the final two weeks of the stress procedure. As expected, these rats coped better with the stress at the end of six weeks. This graph shows the effects of stress and antidepressants on the rat's behaviour in the Forced Swim (Porsolt) Test. Higher bars indicate more "depressed" behaviour. The second pair of bars, representing the stressed rats who got placebo injections, is a lot higher than the first pair of bars representing rats who were not subjected to any stress. In other words, stress made rats "depressed" - no surprise. The other four pairs of bars are pretty much the same height as the first pair; these are rats who got antidepressants, showing that they were resistant to the effects of stress.

The crucial finding is that the white and the black bars are all pretty much the same height. The black bars represent animals who were given injections of methylazoxymethanol (MAM), a cytostatic toxin which blocks cell division (rather like cancer chemotherapy). As you can see, MAM had no effect at all on behaviour in the swim test. It had no effect on most other tests, although it did seem to make the rats more anxious in one experiment.

However, MAM powerfully inhibited neurogenesis. This second graph shows the number of hippocampal cells expressing KI-67, a protein which is a marker of neuroproliferation. As expected, stress reduced neurogenesis and antidepressants increased it. MAM (black bars again) reduced neurogenesis, and in particular, it completely blocked the ability of antidepressants to increase it.

But as we saw earlier, MAM did not stop antidepressants from protecting rats against stress. So, the authors concluded, neurogenesis is not necessary for antidepressants to work. This contradicts the landmark finding of Santarelli et. al. - why the discrepency? There are so many differences between the two experiments that there could be any number of explanations - the current study used rats, while Santarelli used mice, for one thing, and that could well be important. Whatever the reason, this result suggests at the least that neurogenesis is not the only mechanism by which antidepressants counteract the effects of stress in animals.

The most interesting aspect of this paper, to my mind, was an essentially unrelated new finding. Stress was found to reduce the volume of several areas of the rat's brain, including the hippocampus and also the medial prefrontal cortex (mPFC). Unlike the hippocampus, this is an area known to be involved in motivation and emotion. Importantly, the authors found that following stress, the mPFC did not shrink because neurones were dying or because fewer neurones were being born, but rather because the existing neurones were changing shape - stress caused atrophy of the dendritic spines which branch out from neurones. Dendrites are essential for communication between neurones.

As you can see in the drawings above, stress (the middle column) caused shrinking and stunting of the dendrites in pyrimidal neurones from three areas relative to the unstressed rats (left), while those rats recieving antidepressants as well as stress showed no such effect (right). The cytostatic MAM had no effect whatsoever on dendrites. Further work found that antidepressants increase expression of NCAM1, a protein which is involved in dendritic growth.

So what does this mean? Well, for one thing, it doesn't prove that antidepressants work by increasing dendritic branching. Cheekily, the authors come close to implying this in their choice of title for the paper, but the published evidence shows no direct evidence for this. To find out, you would have to show that blocking the effects of antidepressants on dendrites also blocks their beneficial effects. I suspect this is what the authors are now working hard to try to do, but they haven't done so yet.

It also doesn't mean that taking Prozac will change the shape of your brain cells. It might well do, but this was a study in rats given huge doses of antidepressants (by human standards), so we really don't know whether the findings apply to humans. On the other hand, if Prozac changes the shape of your cells, this study suggests that stressful situations do too - and Prozac, if anything, will put your cells back to "normal".

Finally, I don't want to suggest that the neurogenesis theory of depression is now "dead". In neuroscience, theories never live or die on the basis of single experiments (unlike in physics). But it does suggest that the much-blogged-about neurogenesis hypothesis is not the whole story. Depression isn't just a case of too little serotonin, and it isn't just a case of too little neurogenesis or too little BDNF either.


J M Bessa, D Ferreira, I Melo, F Marques, J J Cerqueira, J A Palha, O F X Almeida, N Sousa (2008). The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling Molecular Psychiatry DOI: 10.1038/mp.2008.119

BBC: Bullies have Bad Brains

It was only last week that fMRI explained human hatred. Now it's revealed why some kids are horrible to others. Behold -

• "Bullying tendency wired in brain"

• "Bullies' brains may be hardwired to have sadistic tendencies"

• "Bullies' brains may be wired differently"

At least according to the BBC. You may not be surprised to learn that I'm skeptical. The Neurocritic is too, and indeed he beat me to it on this one, having critiqued the paper in question, "Atypical Empathetic Responses in Adolescents with Aggressive Conduct Disorder: A functional MRI Investigation" (here), remarkably quickly.

So I wasn't going to post about this study, but then The Onion covered it and inspired me to write something. Or rather, I'm going to write about the BBC's story, which was impressively rubbish even by the standards of neuro-journalism.

Basically, all of the statements I quoted at the top of this post are nonsense. They're science fiction. For one thing, this study wasn't about "bullies", but teenage boys diagnosed with severe "Conduct Disorder" (CD) who had committed multiple serious crimes. That's just nitpicking though. The study found, using fMRI, that when you show these CD-diagnosed boys videos of people suffering pain, different parts of their brain activate, compared to a control group of nice, non-violent boys. On some interpretations these areas included the brain's "pleasure centers" although this is controversial (and according to one commentator, it may be all based on someone flunking Anatomy 101).

I've previously berated laymen and journalists (and all-too-many neuroscientists) for being mystified by coloured blobs on the brain. They see them as revealing profound truths about humanity, and in particular, they see them as pointing to "nature" over "nurture" explanations for behaviour. This is rarely explicitly stated, but the BBC did so with the line "Bullies' brains may be hardwired to have sadistic tendencies". Essentially, they are implying that there is something biologically wrong with the brains of bullies which leads to them taking pleasure in the pain of others.

Is this completely unfounded? After all, the study did find differences in the brains of the bullies vs. the normal kids. Surely that means they were "wired differently", maybe even "hardwired" differently? Well, yes, but only in an utterly trivial sense. Everything we do is the result of our brain activity - and every difference between two people is a result of differences in the "wiring" of their brains. The only reason that you're not sitting here like me, writing a cynical blog post about neuroscience, is that you have the good fortune to have a brain wired differently from mine. The only reason I wrote the word "cynical" in that last sentence rather than, er, "snarky", is that my brain was wired that way. And so on.

Brains get wired the way they do through the interacting influence of genes (which tell your neurons how to grow and how to connect up during brain development) and the environment (e.g. as you learn to do something, new connections between your neurons are formed, sometimes leading to massive reorganization of the brain - a fascinating topic in itself).

So, that one person's brain is "wired differently" to another person's is a completely mundane fact. In fact it's as dull as saying that no two people have the same fingerprints. It tells you nothing about how it got to be wired the way it did, and in particular it tells you nothing about whether it was "hardwired" to be that way, i.e. genetically determined. Just by reading this post, your brain has got rewired! So even if you accept that this fMRI study found that bullies take pleasure in watching people suffer (dubious as I mentioned above), this tells you nothing about why. Maybe they were brought up to be sadistic. Maybe they see other people suffering a lot, and have got used to it.

So when the BBC quote Dr Mike Eslea as saying

A better understanding of the biological basis of these things is good to have but the danger is it causes people to leap to biological solutions - drugs - rather than other behavioural solutions

They should perhaps heed his warning rather than "biologizing" bullying so keenly.

The interesting thing about this is that the BBC journalist was probably not stupid. He or she is just human. I think we feel intuitively that any biological difference between two groups of people implies a biological cause for that difference, because we intuitively have a dualistic concept of the relationship between the mind and the brain. Mind and brain are separate entities. We can just about accept that the brain (biological) can influence behaviour (psychological), although we find this idea outlandish and vaguely disturbing, because we think it undermines the idea of "free will". But we can't see how behaviour could influence the brain. Hence the headline "Bullying tendency wired in brain". It's common sense, but it's also nonsense.

BBC: Bullies have Bad Brains

It was only last week that fMRI explained human hatred. Now it's revealed why some kids are horrible to others. Behold -

• "Bullying tendency wired in brain"

• "Bullies' brains may be hardwired to have sadistic tendencies"

• "Bullies' brains may be wired differently"

At least according to the BBC. You may not be surprised to learn that I'm skeptical. The Neurocritic is too, and indeed he beat me to it on this one, having critiqued the paper in question, "Atypical Empathetic Responses in Adolescents with Aggressive Conduct Disorder: A functional MRI Investigation" (here), remarkably quickly.

So I wasn't going to post about this study, but then The Onion covered it and inspired me to write something. Or rather, I'm going to write about the BBC's story, which was impressively rubbish even by the standards of neuro-journalism.

Basically, all of the statements I quoted at the top of this post are nonsense. They're science fiction. For one thing, this study wasn't about "bullies", but teenage boys diagnosed with severe "Conduct Disorder" (CD) who had committed multiple serious crimes. That's just nitpicking though. The study found, using fMRI, that when you show these CD-diagnosed boys videos of people suffering pain, different parts of their brain activate, compared to a control group of nice, non-violent boys. On some interpretations these areas included the brain's "pleasure centers" although this is controversial (and according to one commentator, it may be all based on someone flunking Anatomy 101).

I've previously berated laymen and journalists (and all-too-many neuroscientists) for being mystified by coloured blobs on the brain. They see them as revealing profound truths about humanity, and in particular, they see them as pointing to "nature" over "nurture" explanations for behaviour. This is rarely explicitly stated, but the BBC did so with the line "Bullies' brains may be hardwired to have sadistic tendencies". Essentially, they are implying that there is something biologically wrong with the brains of bullies which leads to them taking pleasure in the pain of others.

Is this completely unfounded? After all, the study did find differences in the brains of the bullies vs. the normal kids. Surely that means they were "wired differently", maybe even "hardwired" differently? Well, yes, but only in an utterly trivial sense. Everything we do is the result of our brain activity - and every difference between two people is a result of differences in the "wiring" of their brains. The only reason that you're not sitting here like me, writing a cynical blog post about neuroscience, is that you have the good fortune to have a brain wired differently from mine. The only reason I wrote the word "cynical" in that last sentence rather than, er, "snarky", is that my brain was wired that way. And so on.

Brains get wired the way they do through the interacting influence of genes (which tell your neurons how to grow and how to connect up during brain development) and the environment (e.g. as you learn to do something, new connections between your neurons are formed, sometimes leading to massive reorganization of the brain - a fascinating topic in itself).

So, that one person's brain is "wired differently" to another person's is a completely mundane fact. In fact it's as dull as saying that no two people have the same fingerprints. It tells you nothing about how it got to be wired the way it did, and in particular it tells you nothing about whether it was "hardwired" to be that way, i.e. genetically determined. Just by reading this post, your brain has got rewired! So even if you accept that this fMRI study found that bullies take pleasure in watching people suffer (dubious as I mentioned above), this tells you nothing about why. Maybe they were brought up to be sadistic. Maybe they see other people suffering a lot, and have got used to it.

So when the BBC quote Dr Mike Eslea as saying

A better understanding of the biological basis of these things is good to have but the danger is it causes people to leap to biological solutions - drugs - rather than other behavioural solutions

They should perhaps heed his warning rather than "biologizing" bullying so keenly.

The interesting thing about this is that the BBC journalist was probably not stupid. He or she is just human. I think we feel intuitively that any biological difference between two groups of people implies a biological cause for that difference, because we intuitively have a dualistic concept of the relationship between the mind and the brain. Mind and brain are separate entities. We can just about accept that the brain (biological) can influence behaviour (psychological), although we find this idea outlandish and vaguely disturbing, because we think it undermines the idea of "free will". But we can't see how behaviour could influence the brain. Hence the headline "Bullying tendency wired in brain". It's common sense, but it's also nonsense.

Shock and Cure

For regular readers (and Google Analytics assures me I do have some - hello), this post may be a bit of a change of pace.

Many mental health blogs have alerted readers to the case of Ray Sandford, a Minnesota man who's being given ECT (electroconvulsive therapy), as an outpatient, against his wishes. Encouraging people to write to the Governor of Minnesota in protest, Philip Dawdy of the Furious Seasons said

I am officially neutral on voluntary ECT--if someone wants it, it's their brain--but involuntary ECT is barbarous and amounts to torture. If anyone would like to defend involuntary ECT, let me hear from you. If you make a good argument, I might even post it.

I have nothing to say about Mr Sandford's case, but I'll defend involuntary ECT in general. Why? Because I believe the evidence supports it, but if I'm honest, the reason I'm writing this is because of my granddad.

During the 1940s and 1950s my grandfather, at the time a junior doctor, suffered from several bouts of severe depression. Antidepressants not yet existing, the only available treatment was ECT. He was given it - with his consent - and it worked. In fact, he was given ECT using a number of different stimulus parameters and he says that bilateral treatment rapidly lifted his mood while unilateral was useless.

ECT was the only thing that could lift my grandfather out of his illness. Fortunately, he never became so ill that he was unable to give his consent. But if he had - if his depression had ever got so bad that he could not summon up the courage to receive treatment, if he had given up on life or just given up talking - then all this would have meant was that he needed ECT even more. If his illness had robbed him of the wish to get better, as I know it nearly did, it would have been a tradgety for his doctors to not have helped him fight back.

• Sometimes consent is a luxury
  

My argument is that involuntary ECT is sometimes justified because in psychiatry, involuntary treatment is sometimes necessary, and ECT is sometimes the only treatment that works. Some people object to all forced treatments, whether ECT, or medication, or anything else. I respect this, and I agree that in principle, treatment should only ever be given with consent. Adults should not be treated if they have made an informed choice not to be - as patients we have a right to autonomy, including a right to refuse treatment and even a right to die.

However - in psychiatry, things are not so simple. It's often those who are most ill, those who have the most to gain from treatment, who are most likely to refuse it. From my own experience I know how even moderate depression can warp your thinking - severe illness can lead people to be, temporarily, unable to make informed decisions. They may not know that they are ill, or they may not be able believe that there is any hope of recovery.

If someone is in such a state - whether they are extremely depressed, manic, or psychotic - it would be cruel and neglectful not to treat them, by any means necessary. Surely that's common sense - if your friend was blind drunk and tried to drive home because he thought he was completely sober, you'd be responsible for his safety if you didn't try to stop him. If I got drunk and started acting stupidly I'd want my friends to look after me, and when I woke up the next morning, I'd be angry if they hadn't.

Many people are concerned about psychiatrists forcibly treating patients as a punishment or as a way of keeping them quiet. I don't know how often this happens, but whenever it does, it needs to be stopped. No-one would disagree with that. But these aren't the only reasons why people are treated without their consent. Sometimes it really is for their own good.

The costs and the benefits of any treatment have be balanced, which is difficult, and it may be difficult to decide whether someone is able to give informed consent. Mistakes will be made. This is why I have no opinion on Ray Sandford. He may or may be the victim of a mistake, and I don't think anyone who hasn't met the man can judge that.

• ECT works

ECT of course has a bad reputation. Dawdy calls it "barbarous" - he's much more restrained than some. It's true that ECT is a crude procedure, in the sense that we don't know how it works. But it does work. There's very strong evidence that ECT is highly effective for depression - ECT is much more effective than the placebo "sham ECT", showing that the benefits are real and not simply placebo. ECT is also effective in other acute psychiatric states; e.g. according to the U.S. Surgeon General's office

Accumulated clinical experience—later confirmed in controlled clinical trials, which included the use of simulated or “sham” ECT as a control — determined ECT to be highly effective against severe depression, some acute psychotic states, and mania. No controlled study has shown any other treatment to have superior efficacy to ECT in the treatment of depression.

Any psychiatrist who has used it will agree. I know that many people feel very strongly about ECT, including some who are likely to be reading this. Some people have had very negative experiences. But not everyone has. I was going to cite a list of references to surveys on patient views of ECT here, but I decided against it. There are dozens of papers and as many different findings.

Rose et. al. (2003) reviewed the literature and found an enormous range of opinions, from strongly positive to strongly negative, amongst ECT patients. This paper is fairly skeptical, and reports that a third of people given ECT report memory problems. My grandfather didn't - his memory is fading now, because he's 85, but he managed to carry on a career as a very succesful doctor for 50 years. The debate over the costs and benefits of ECT is an important one. This paper appeared in the British Medical Journal, the official publication of the British medical establishment. The debate is not being suppressed. I've read this paper. I'm not ignoring the voices of the ECT survivior movement, but they are not the only ones.

ECT is a controversial therapy, but there's no doubt that it has helped many people, and in some cases it is certainly the only treatment that works. Official guidelines, such as those of the British NICE agency, all advise that ECT should only be used as a last resort where other treatments have failed. No-one is rushing to give ECT to everyone, but when all else has failed, it can work. And if someone is too ill to give their consent, and all else has failed, forced ECT remains an option. It is an extreme one, but I can honestly say that if I, or anyone in my family, ever became so ill that this was the only option, I would want it done.

• Conflicts of Interest?
  

Just to be clear: I have never received or been offered ECT, but like my grandfather I suffered from moderate-to-severe depression for a long time. I'm currently taking 40mg per day Celexa (citalopram.) Like ECT, SSRIs have a bad reputation. My experiences have been entirely positive. With citalopram I've gained energy, optimism, and the ability to enjoy life. The worst thing I've suffered has been a dry mouth. In general, I am strongly pro-psychiatry, and I work as a researcher on the neurobiology of depression and antidepressant action. I'm not medically qualified. I am a big fan of David Healy (like me, a defender of ECT), but have a very low opinion of people like Szasz and Laing.

Update : 12 . 11 . 2008 16:20 GMT
Philip Dawdy put a portion of this post up on Furious Seasons, where it sparked a, well, a lively debate.

Thanks to an anonymous commenator (below) who did some googling and found that Mr Sandford's residence, Victory House, seems to be a home for people suffering from Alzheimer's Disease. Although I still make no comment on Mr Sandford, this might be of interest to any who dislike the idea of involuntary "outpatient" ECT.

Shock and Cure

For regular readers (and Google Analytics assures me I do have some - hello), this post may be a bit of a change of pace.

Many mental health blogs have alerted readers to the case of Ray Sandford, a Minnesota man who's being given ECT (electroconvulsive therapy), as an outpatient, against his wishes. Encouraging people to write to the Governor of Minnesota in protest, Philip Dawdy of the Furious Seasons said

I am officially neutral on voluntary ECT--if someone wants it, it's their brain--but involuntary ECT is barbarous and amounts to torture. If anyone would like to defend involuntary ECT, let me hear from you. If you make a good argument, I might even post it.

I have nothing to say about Mr Sandford's case, but I'll defend involuntary ECT in general. Why? Because I believe the evidence supports it, but if I'm honest, the reason I'm writing this is because of my granddad.

During the 1940s and 1950s my grandfather, at the time a junior doctor, suffered from several bouts of severe depression. Antidepressants not yet existing, the only available treatment was ECT. He was given it - with his consent - and it worked. In fact, he was given ECT using a number of different stimulus parameters and he says that bilateral treatment rapidly lifted his mood while unilateral was useless.

ECT was the only thing that could lift my grandfather out of his illness. Fortunately, he never became so ill that he was unable to give his consent. But if he had - if his depression had ever got so bad that he could not summon up the courage to receive treatment, if he had given up on life or just given up talking - then all this would have meant was that he needed ECT even more. If his illness had robbed him of the wish to get better, as I know it nearly did, it would have been a tradgety for his doctors to not have helped him fight back.

• Sometimes consent is a luxury
  

My argument is that involuntary ECT is sometimes justified because in psychiatry, involuntary treatment is sometimes necessary, and ECT is sometimes the only treatment that works. Some people object to all forced treatments, whether ECT, or medication, or anything else. I respect this, and I agree that in principle, treatment should only ever be given with consent. Adults should not be treated if they have made an informed choice not to be - as patients we have a right to autonomy, including a right to refuse treatment and even a right to die.

However - in psychiatry, things are not so simple. It's often those who are most ill, those who have the most to gain from treatment, who are most likely to refuse it. From my own experience I know how even moderate depression can warp your thinking - severe illness can lead people to be, temporarily, unable to make informed decisions. They may not know that they are ill, or they may not be able believe that there is any hope of recovery.

If someone is in such a state - whether they are extremely depressed, manic, or psychotic - it would be cruel and neglectful not to treat them, by any means necessary. Surely that's common sense - if your friend was blind drunk and tried to drive home because he thought he was completely sober, you'd be responsible for his safety if you didn't try to stop him. If I got drunk and started acting stupidly I'd want my friends to look after me, and when I woke up the next morning, I'd be angry if they hadn't.

Many people are concerned about psychiatrists forcibly treating patients as a punishment or as a way of keeping them quiet. I don't know how often this happens, but whenever it does, it needs to be stopped. No-one would disagree with that. But these aren't the only reasons why people are treated without their consent. Sometimes it really is for their own good.

The costs and the benefits of any treatment have be balanced, which is difficult, and it may be difficult to decide whether someone is able to give informed consent. Mistakes will be made. This is why I have no opinion on Ray Sandford. He may or may be the victim of a mistake, and I don't think anyone who hasn't met the man can judge that.

• ECT works

ECT of course has a bad reputation. Dawdy calls it "barbarous" - he's much more restrained than some. It's true that ECT is a crude procedure, in the sense that we don't know how it works. But it does work. There's very strong evidence that ECT is highly effective for depression - ECT is much more effective than the placebo "sham ECT", showing that the benefits are real and not simply placebo. ECT is also effective in other acute psychiatric states; e.g. according to the U.S. Surgeon General's office

Accumulated clinical experience—later confirmed in controlled clinical trials, which included the use of simulated or “sham” ECT as a control — determined ECT to be highly effective against severe depression, some acute psychotic states, and mania. No controlled study has shown any other treatment to have superior efficacy to ECT in the treatment of depression.

Any psychiatrist who has used it will agree. I know that many people feel very strongly about ECT, including some who are likely to be reading this. Some people have had very negative experiences. But not everyone has. I was going to cite a list of references to surveys on patient views of ECT here, but I decided against it. There are dozens of papers and as many different findings.

Rose et. al. (2003) reviewed the literature and found an enormous range of opinions, from strongly positive to strongly negative, amongst ECT patients. This paper is fairly skeptical, and reports that a third of people given ECT report memory problems. My grandfather didn't - his memory is fading now, because he's 85, but he managed to carry on a career as a very succesful doctor for 50 years. The debate over the costs and benefits of ECT is an important one. This paper appeared in the British Medical Journal, the official publication of the British medical establishment. The debate is not being suppressed. I've read this paper. I'm not ignoring the voices of the ECT survivior movement, but they are not the only ones.

ECT is a controversial therapy, but there's no doubt that it has helped many people, and in some cases it is certainly the only treatment that works. Official guidelines, such as those of the British NICE agency, all advise that ECT should only be used as a last resort where other treatments have failed. No-one is rushing to give ECT to everyone, but when all else has failed, it can work. And if someone is too ill to give their consent, and all else has failed, forced ECT remains an option. It is an extreme one, but I can honestly say that if I, or anyone in my family, ever became so ill that this was the only option, I would want it done.

• Conflicts of Interest?
  

Just to be clear: I have never received or been offered ECT, but like my grandfather I suffered from moderate-to-severe depression for a long time. I'm currently taking 40mg per day Celexa (citalopram.) Like ECT, SSRIs have a bad reputation. My experiences have been entirely positive. With citalopram I've gained energy, optimism, and the ability to enjoy life. The worst thing I've suffered has been a dry mouth. In general, I am strongly pro-psychiatry, and I work as a researcher on the neurobiology of depression and antidepressant action. I'm not medically qualified. I am a big fan of David Healy (like me, a defender of ECT), but have a very low opinion of people like Szasz and Laing.

Update : 12 . 11 . 2008 16:20 GMT
Philip Dawdy put a portion of this post up on Furious Seasons, where it sparked a, well, a lively debate.

Thanks to an anonymous commenator (below) who did some googling and found that Mr Sandford's residence, Victory House, seems to be a home for people suffering from Alzheimer's Disease. Although I still make no comment on Mr Sandford, this might be of interest to any who dislike the idea of involuntary "outpatient" ECT.

Life is Actually Quite Complicated

In this excellent post, new blogger Mike Eslea (the Punk Psychologist) takes British newspapers to task for their sensationalist coverage of some new statistics about knife crime. For non-British readers, I should explain that knife crime is a hot button issue in this country at the moment, with the narrative that there's a "knife crime epidemic" in progress being widely accepted.

As Eslea explains, when the new crime statistics were released, all of the headlines talked of a "22% rise" in knife incidents. This sounds pretty dramatic, and straightforward - 22% more stabblings, oh no! But in fact the picture is much less clear - most of this rise was probably due to changes in the way such crimes are reported, and even defining knife crime is not as easy as it seems. He also notes that last year the Times managed to extract the headline "Knife Crime Doubles In Two Years", based on a report which found nothing of the sort, through careful cherry-picking of the statistics. You should read the whole of the post - it's enlightening (and if you don't, me and Eslea will stab you up.)

Anyway, what's interesting is that this is just the kind of thing that we also see in much of science journalism. Ben Goldacre's excellent Bad Science is full of examples of the way in which the media mislead in their coverage of scientific and medical research. Reporting on violence, drugs, teenage pregnancy and other social sins often misleads for exactly the same reasons - i.e. statistics are cherry-picked to support the most dramatic conclusions, caveats and methodological weaknesses are ignored, and evidence which doesn't fit with the narrative are not reported on at all (in this case the narrative is "knife crime epidemic!" but we have also had "autism epidemic!", "diet determines health!" etc. etc.) Science, medicine, or crime, the numbers get spun in the same ways.

The basic problem, as I see it, is that people just don't like doubt. We want a clear story, even if the available evidence doesn't support any firm conclusions. Look at the Daily Mail's regular headlines about something causing or preventing cancer - any epidemiologist knows that establishing risk factors for cancer is a very difficult job, and there is a huge amount of uncertainty, and a lot of the research out there is crap. For the Mail, on the other hand, one small study constitutes proof. Until the next small study comes along and proves that what we thought cured cancer actually causes it, and vice versa. Experts despair at this, but they're in a minority.

This great BBC article accuses politicians of being unwilling to admit doubt about whether policies will work. To be fair to them, though, they're in an impossible position, because the public and the media demand certainty. We know that knife crime is skyrocketing and we want someone who knows how to stop it. By which I mean that most of us do. I don't - from what I've read about knife crime, nationwide it probably isn't rising, or maybe it is a bit, but in some parts of the country and among some communities it could be rising a lot, although even if it is, we have no idea why, and we don't have any proven ways of improving things... The point is that it's complicated. There's a lot of evidence to consider and most of it's flawed in one way or another. That's true for neuroscience, and it's also true for public policy.