Bipolar Kids: You Read It Here First

Last year, I discussed the controvery over the proposed new childhood syndrome of "Temper Disregulation Disorder with Dysphoria" (TDDD). It may be included in the upcoming revision of the psychiatric bible, DSM-V.

Back then, I said:

TDDD has been proposed in order to reduce the number of children being diagnosed with pediatric bipolar disorder... many people agree that pediatric bipolar is being over-diagnosed.

So we can all sympathize with the sentiment behind TDDD - but this is fighting fire with fire. Is the only way to stop kids getting one diagnosis, to give them another one? Should we really be creating diagnoses for more or less "strategic" purposes?

Now, a bunch of psychiatrists have written to the Journal of Clinical Psychiatry to express their concerns over the proposed diagnosis. They make the same point that I did:

We believe that the creation of a new, unsubstantiated diagnosis in order to prevent misapplication of a different diagnosis is misguided and a step backward for the progression of psychiatry as a rational scientific discipline.

Although they go into much more detail in critiquing the evidence held up in favor of the idea of TDDD. They also point out that it is rather optimistic to think, as some people apparantly do, that if we were to diagnose kids with TDDD, as opposed to childhood bipolar, we'd save them from getting nasty bipolar medications.

As they say, the risk is that drug companies would just get their drugs licensed to treat TDDD instead. Same drugs, different label. It would be fairly easy: just for starters, there are plenty of sedative drugs, such as atypical antipsychotics, which would certainly alter or mask the "symptoms" of TDDD, in the short term. Doing a clinical trial and showing that these drugs "work" would be easy. It wouldn't mean they actually worked, or that TDDD actually existed.

They also point out that the public perception of child psychiatry has already been harmed by the proposal of TDDD, and would suffer further if it were to become official.

Well, of course it would, and quite rightly so. That would be a sign that child psychiatry is so out of control that, literally, the only way it can stop diagnosing children, is to diagnose them with something else!

The same issue of the the same journal features another paper, claiming that "pediatric bipolar disorder" has a prevalence rate of 1.8%, and that rates of diagnosis of childhood bipolar are not higher in the USA than elsewhere, contrary to popular belief based on evidence.

Their data are a bunch of epidemiological studies on bipolar disorder. One of which included children up to the age of...21. The majority included kids of 17 or 18.

So, er, not children at all, then.


The older the "children" in the study, the more bipolar that study found. Everyone knows that bipolar disorder typically starts in late adolescence. That's the orthodoxy and it has been since Kraepelin. It's right there at the top of the Wikipedia page. That's not pediatric bipolar, that's just normal bipolar.

All the recent controversy is about bipolar in children. As in, like, 8 year olds. Yet this paper is still titled "Meta-analysis of epidemiologic studies of pediatric bipolar disorder". The senior author on this paper also signed the paper criticizing TDDD.

This, then, is the state of the debate over the future of our children.

P.S. I've just noticed that in the latest draft of DSM-V, TDDD has been renamed. It's now called "DMDD". What's next? DUDD? DEDD? P-DIDDY ?

Axelson DA, Birmaher B, Findling RL, Fristad MA, Kowatch RA, Youngstrom EA, Arnold EL, Goldstein BI, Goldstein TR, Chang KD, Delbello MP, Ryan ND, & Diler RS (2011). Concerns regarding the inclusion of temper dysregulation disorder with dysphoria in the DSM-V The Journal of clinical psychiatry PMID: 21672494

Van Meter AR, Moreira AL, & Youngstrom EA (2011). Meta-analysis of epidemiologic studies of pediatric bipolar disorder. The Journal of clinical psychiatry PMID: 21672501

Bipolar Kids: You Read It Here First

Last year, I discussed the controvery over the proposed new childhood syndrome of "Temper Disregulation Disorder with Dysphoria" (TDDD). It may be included in the upcoming revision of the psychiatric bible, DSM-V.

Back then, I said:

TDDD has been proposed in order to reduce the number of children being diagnosed with pediatric bipolar disorder... many people agree that pediatric bipolar is being over-diagnosed.

So we can all sympathize with the sentiment behind TDDD - but this is fighting fire with fire. Is the only way to stop kids getting one diagnosis, to give them another one? Should we really be creating diagnoses for more or less "strategic" purposes?

Now, a bunch of psychiatrists have written to the Journal of Clinical Psychiatry to express their concerns over the proposed diagnosis. They make the same point that I did:

We believe that the creation of a new, unsubstantiated diagnosis in order to prevent misapplication of a different diagnosis is misguided and a step backward for the progression of psychiatry as a rational scientific discipline.

Although they go into much more detail in critiquing the evidence held up in favor of the idea of TDDD. They also point out that it is rather optimistic to think, as some people apparantly do, that if we were to diagnose kids with TDDD, as opposed to childhood bipolar, we'd save them from getting nasty bipolar medications.

As they say, the risk is that drug companies would just get their drugs licensed to treat TDDD instead. Same drugs, different label. It would be fairly easy: just for starters, there are plenty of sedative drugs, such as atypical antipsychotics, which would certainly alter or mask the "symptoms" of TDDD, in the short term. Doing a clinical trial and showing that these drugs "work" would be easy. It wouldn't mean they actually worked, or that TDDD actually existed.

They also point out that the public perception of child psychiatry has already been harmed by the proposal of TDDD, and would suffer further if it were to become official.

Well, of course it would, and quite rightly so. That would be a sign that child psychiatry is so out of control that, literally, the only way it can stop diagnosing children, is to diagnose them with something else!

The same issue of the the same journal features another paper, claiming that "pediatric bipolar disorder" has a prevalence rate of 1.8%, and that rates of diagnosis of childhood bipolar are not higher in the USA than elsewhere, contrary to popular belief based on evidence.

Their data are a bunch of epidemiological studies on bipolar disorder. One of which included children up to the age of...21. The majority included kids of 17 or 18.

So, er, not children at all, then.


The older the "children" in the study, the more bipolar that study found. Everyone knows that bipolar disorder typically starts in late adolescence. That's the orthodoxy and it has been since Kraepelin. It's right there at the top of the Wikipedia page. That's not pediatric bipolar, that's just normal bipolar.

All the recent controversy is about bipolar in children. As in, like, 8 year olds. Yet this paper is still titled "Meta-analysis of epidemiologic studies of pediatric bipolar disorder". The senior author on this paper also signed the paper criticizing TDDD.

This, then, is the state of the debate over the future of our children.

P.S. I've just noticed that in the latest draft of DSM-V, TDDD has been renamed. It's now called "DMDD". What's next? DUDD? DEDD? P-DIDDY ?

Axelson DA, Birmaher B, Findling RL, Fristad MA, Kowatch RA, Youngstrom EA, Arnold EL, Goldstein BI, Goldstein TR, Chang KD, Delbello MP, Ryan ND, & Diler RS (2011). Concerns regarding the inclusion of temper dysregulation disorder with dysphoria in the DSM-V The Journal of clinical psychiatry PMID: 21672494

Van Meter AR, Moreira AL, & Youngstrom EA (2011). Meta-analysis of epidemiologic studies of pediatric bipolar disorder. The Journal of clinical psychiatry PMID: 21672501

Neuroplasticity Revisited

A fascinating case report details a remarkable recovery from serious brain injury: Characterization of recovery and neuropsychological consequences of orbitofrontal lesion.

The patient "M. S." was a previously healthy 29 year old Israeli graduate student who suffered injuries in a terrorist attack. As the MRI scans above show, she lost large parts of her orbitofrontal cortex and ventromedial prefrontal cortex, although the left side was only partially affected. She also lost her right eye.

These areas are known to be involved in emotion and decision making. Her lesions are somewhat similar to those suffered by the famous Phineas Gage, and as we'll see, her symptoms were too - but only temporarily.

One year after the injury...

M.S.’s complaints included a sense of general fatigue, loss of taste and smell, difficulty concentrating and emotional changes including irritability, lability, depression and social isolation. She reported failing to make new social contacts, having lost most of her old friends, and a diminished need for social relationships.

M.S. reported that family and friends commented on her change from a quiet and pleasant person to a rude, annoying, uninhibited, and unstoppable talkative person following the injury... M.S. had become apathetic, without a sense of time, and with no plans for the future.

On examination, M.S. was fully cooperative. She had difficulty concentrating and required frequent breaks. She appeared euphoric, laughed frequently and inappropriately, talked too much,made inappropriate remarks and jokes, yawned loudly... M.S. found it difficult to sit still and showed utilization behavior, continuously fidgeting and touching objects on the table. She had a tendency to continue performing tasks after completion was stated.

These personality and mood changes are reminisicent of those Phineas Gage suffered. Strangely, she scored 33 on the self-report depression scale the BDI, which corresponds to "severe depression", but from the description she doesn't sound depressed in the normal sense. These scales were not designed for people with brain lesions. Her cognitive function and memory was mostly normal but with clear impairments on some tests.

Anyway, that was after 1 year, and if that were the end it would be a rather sad story, but there's a happy ending. After this she got psychotherapy and rehabilitation treatment. 7 years later she had a follow-up assessment and she was much improved.

Her mood, attention-span and so forth were reported as normal. She struggled with her graduate studies, finding them more difficult than before the injury, and had eventually quit them, but she'd got a new job. She had recently got married.

Her performance on neuropsychological tests designed to measure prefrontal cortex damage was mostly normal, and she did much better on the ones that she used to be impaired on. She still did poorly on the Iowa Gambling Task, which is very sensitive vmPFC damage.

Overall, though, she had made a "magnificent" recovery despite losing a large chunk of her brain. I've previously been skeptical of some of the stronger claims of neuroplasticity or "brain remodelling", but some parts of the brain are more plastic than others and the prefrontal cortex seems to be one of the most flexible.

Fisher T, Shamay-Tsoory SG, Eran A, & Aharon-Peretz J (2011). Characterization of recovery and neuropsychological consequences of orbitofrontal lesion: A case study. Neurocase, 17 (3), 285-93 PMID: 21667397

Neuroplasticity Revisited

A fascinating case report details a remarkable recovery from serious brain injury: Characterization of recovery and neuropsychological consequences of orbitofrontal lesion.

The patient "M. S." was a previously healthy 29 year old Israeli graduate student who suffered injuries in a terrorist attack. As the MRI scans above show, she lost large parts of her orbitofrontal cortex and ventromedial prefrontal cortex, although the left side was only partially affected. She also lost her right eye.

These areas are known to be involved in emotion and decision making. Her lesions are somewhat similar to those suffered by the famous Phineas Gage, and as we'll see, her symptoms were too - but only temporarily.

One year after the injury...

M.S.’s complaints included a sense of general fatigue, loss of taste and smell, difficulty concentrating and emotional changes including irritability, lability, depression and social isolation. She reported failing to make new social contacts, having lost most of her old friends, and a diminished need for social relationships.

M.S. reported that family and friends commented on her change from a quiet and pleasant person to a rude, annoying, uninhibited, and unstoppable talkative person following the injury... M.S. had become apathetic, without a sense of time, and with no plans for the future.

On examination, M.S. was fully cooperative. She had difficulty concentrating and required frequent breaks. She appeared euphoric, laughed frequently and inappropriately, talked too much,made inappropriate remarks and jokes, yawned loudly... M.S. found it difficult to sit still and showed utilization behavior, continuously fidgeting and touching objects on the table. She had a tendency to continue performing tasks after completion was stated.

These personality and mood changes are reminisicent of those Phineas Gage suffered. Strangely, she scored 33 on the self-report depression scale the BDI, which corresponds to "severe depression", but from the description she doesn't sound depressed in the normal sense. These scales were not designed for people with brain lesions. Her cognitive function and memory was mostly normal but with clear impairments on some tests.

Anyway, that was after 1 year, and if that were the end it would be a rather sad story, but there's a happy ending. After this she got psychotherapy and rehabilitation treatment. 7 years later she had a follow-up assessment and she was much improved.

Her mood, attention-span and so forth were reported as normal. She struggled with her graduate studies, finding them more difficult than before the injury, and had eventually quit them, but she'd got a new job. She had recently got married.

Her performance on neuropsychological tests designed to measure prefrontal cortex damage was mostly normal, and she did much better on the ones that she used to be impaired on. She still did poorly on the Iowa Gambling Task, which is very sensitive vmPFC damage.

Overall, though, she had made a "magnificent" recovery despite losing a large chunk of her brain. I've previously been skeptical of some of the stronger claims of neuroplasticity or "brain remodelling", but some parts of the brain are more plastic than others and the prefrontal cortex seems to be one of the most flexible.

Fisher T, Shamay-Tsoory SG, Eran A, & Aharon-Peretz J (2011). Characterization of recovery and neuropsychological consequences of orbitofrontal lesion: A case study. Neurocase, 17 (3), 285-93 PMID: 21667397

What Is Mental Distress?

"Mental distress" is term which has recently become popular in Britain. It's most often used as a replacement for "mental illness". I'm rather puzzled by this. In this post, I analyze this phrase.

The first thing that leaps out is that "mental" is redundant. What other kind of distress is there? Distress is mental, by default.

This awkward wording seems to be a result of the fact that it's an attempt to fuse some of the features of "mental illness" with some of the implications of "distress", a kind of verbal alchemy. What is mental distress? It's not mental illness, but it's not exactly not mental illness.

Fair enough. Mental illness is a problematic concept, so I'm all in favor of rethinking it. But I'm worried. My worry is that "mental distress" takes the worst features of mental illness and perpetuates them in the guise of being a new and radical idea.

*

Were I to go around making sweeping statements about "the mentally ill" or "people with mental illness", someone would call me out on it, like this - Mental illness is an umbrella term, for all kinds of different experiences! You can't talk about all those people as if they're the same. They're individuals!

Which is quite right.

But it's equally bad to talk about "mental distress" in the same way, and this happens as well. I don't know if mental distress is more often used as a blanket statement, but it's certainly not immune and it's no better. See for example the top Google hit for mental distress:

The first signs of mental distress will be different for the onlooker than it is for the person in distress...

Changes in sleep patterns are a common sign, and appetite may also be affected. Lethargy, low energy levels, feeling antisocial and spending too much time in bed may indicate the onset of depression. Wanting to go out more, needing very little sleep, and feeling highly energetic, creative and sociable, may signal that a person is becoming 'high'.

The first time it happens, the effects of hearing or seeing things that other people don't are likely to be especially dramatic...

Perfectly true, of some people. Not all. In this paragraph "mental distress" seems to mean "bipolar disorder", but in the course of the article it morphs into several other forms. All mental distress.

It's not good enough to make sweeping statements and say "...Of course, everyone is different, but..." That's a cop-out, not a serious attempt to be helpful. It's like being really offensive, and then quickly adding "No offence". If you think everyone's different, talk about them all differently.

I think there's a good case to be made that we shouldn't talk about "mental illness" at all. Take, say, bipolar disorder, social anxiety, and antisocial personality. I'm really not sure that these have anything in common.

They've only been considered to belong to the single category of "psychiatric disorders" for about 50 years. 100 years ago, bipolar was insanity, social anxiety was a character trait, or a 'nervous' problem, and antisocial behaviour was just evil. Different professionals dealt with each one, and few thought of them as being linked.

I'm not saying that we should go back to that. But categories are up for debate. "Mental distress" is a new label, but it's a 50 year old category.

*

My second problem is that "mental distress" implies that everyone who has it, is distressed. But they're just not - at least not if you're using that term as a replacement for "mental illness".

If you're bipolar, and in a manic or hypomanic episode, you might well be the opposite of distressed. More subtly, if you're severely depressed, you might be too low to be distressed. "Distress" implies an acute emotional response. Severe depression paralyses the emotions.

Maybe "mental distress" isn't like normal everyday distress. Maybe mania or depression are mental distress, but not distress. But that's rather confusing. If mental distress isn't distress, what on earth is it? You can't redefine words like that, unless you're Humpty Dumpty.

*

If "mental distress" implies that all mental illness is distress, it also works in reverse: it implies that all distress is a form of pathology. Taken seriously, this would lead to absurd conversations:

"Are you mentally distressed?"
"No, I'm fine. I'm just distressed."

It would also lead to even more people being treated in the mental health system. Already we're told that 1 in 4 people experience mental illness, but almost everyone gets distressed now and again.

You might say that you don't consider mental distress to be a form of pathology. I'm against medicalization! Mental distress isn't an illness! If so, fine, but to be consistent, you're going to have to stop talking about treatments. And causes. And symptoms. Those are all medical words. Discussions of mental distress are chock full of them.

Indeed, if you want to demedicalize "mental distress", you should probably just call it... distress. The "mental" part is a hangover from "mental illness", after all. If you're serious, you ought to junk that and stick with distress.

This would be perfectly clear, it doesn't require us to redefine words or use awkward phrases. Let's give it a go: "Mental illness" is distress. Easy. Unfortunately, when you put it like that, it looks a bit like a sweeping oversimplification, doesn't it? Hmm.

On the other hand, if you're not looking to demedicalize mental illness, why throw out the word illness?

The problem is that many people like the sound of demedicalization, but they're not sure how far they want to go. And in large organizations, some people will want to go much further than others.

Mental health charities seem to be particularly prone to this, so you often see them assuring people that "mental illness is an illness like any other", while simultaneously saying that seeing it just as a medical illness is far too narrow and unhelpful!

This is a serious debate, and it deserves a careful discussion. The compromise term "mental distress" seems to bridge this gap, and allows people with very different views to sound like they're agreeing with each other. This is not the best way to resolve debates like this. People still disagree with each other. They just lack the words to talk about it.

What Is Mental Distress?

"Mental distress" is term which has recently become popular in Britain. It's most often used as a replacement for "mental illness". I'm rather puzzled by this. In this post, I analyze this phrase.

The first thing that leaps out is that "mental" is redundant. What other kind of distress is there? Distress is mental, by default.

This awkward wording seems to be a result of the fact that it's an attempt to fuse some of the features of "mental illness" with some of the implications of "distress", a kind of verbal alchemy. What is mental distress? It's not mental illness, but it's not exactly not mental illness.

Fair enough. Mental illness is a problematic concept, so I'm all in favor of rethinking it. But I'm worried. My worry is that "mental distress" takes the worst features of mental illness and perpetuates them in the guise of being a new and radical idea.

*

Were I to go around making sweeping statements about "the mentally ill" or "people with mental illness", someone would call me out on it, like this - Mental illness is an umbrella term, for all kinds of different experiences! You can't talk about all those people as if they're the same. They're individuals!

Which is quite right.

But it's equally bad to talk about "mental distress" in the same way, and this happens as well. I don't know if mental distress is more often used as a blanket statement, but it's certainly not immune and it's no better. See for example the top Google hit for mental distress:

The first signs of mental distress will be different for the onlooker than it is for the person in distress...

Changes in sleep patterns are a common sign, and appetite may also be affected. Lethargy, low energy levels, feeling antisocial and spending too much time in bed may indicate the onset of depression. Wanting to go out more, needing very little sleep, and feeling highly energetic, creative and sociable, may signal that a person is becoming 'high'.

The first time it happens, the effects of hearing or seeing things that other people don't are likely to be especially dramatic...

Perfectly true, of some people. Not all. In this paragraph "mental distress" seems to mean "bipolar disorder", but in the course of the article it morphs into several other forms. All mental distress.

It's not good enough to make sweeping statements and say "...Of course, everyone is different, but..." That's a cop-out, not a serious attempt to be helpful. It's like being really offensive, and then quickly adding "No offence". If you think everyone's different, talk about them all differently.

I think there's a good case to be made that we shouldn't talk about "mental illness" at all. Take, say, bipolar disorder, social anxiety, and antisocial personality. I'm really not sure that these have anything in common.

They've only been considered to belong to the single category of "psychiatric disorders" for about 50 years. 100 years ago, bipolar was insanity, social anxiety was a character trait, or a 'nervous' problem, and antisocial behaviour was just evil. Different professionals dealt with each one, and few thought of them as being linked.

I'm not saying that we should go back to that. But categories are up for debate. "Mental distress" is a new label, but it's a 50 year old category.

*

My second problem is that "mental distress" implies that everyone who has it, is distressed. But they're just not - at least not if you're using that term as a replacement for "mental illness".

If you're bipolar, and in a manic or hypomanic episode, you might well be the opposite of distressed. More subtly, if you're severely depressed, you might be too low to be distressed. "Distress" implies an acute emotional response. Severe depression paralyses the emotions.

Maybe "mental distress" isn't like normal everyday distress. Maybe mania or depression are mental distress, but not distress. But that's rather confusing. If mental distress isn't distress, what on earth is it? You can't redefine words like that, unless you're Humpty Dumpty.

*

If "mental distress" implies that all mental illness is distress, it also works in reverse: it implies that all distress is a form of pathology. Taken seriously, this would lead to absurd conversations:

"Are you mentally distressed?"
"No, I'm fine. I'm just distressed."

It would also lead to even more people being treated in the mental health system. Already we're told that 1 in 4 people experience mental illness, but almost everyone gets distressed now and again.

You might say that you don't consider mental distress to be a form of pathology. I'm against medicalization! Mental distress isn't an illness! If so, fine, but to be consistent, you're going to have to stop talking about treatments. And causes. And symptoms. Those are all medical words. Discussions of mental distress are chock full of them.

Indeed, if you want to demedicalize "mental distress", you should probably just call it... distress. The "mental" part is a hangover from "mental illness", after all. If you're serious, you ought to junk that and stick with distress.

This would be perfectly clear, it doesn't require us to redefine words or use awkward phrases. Let's give it a go: "Mental illness" is distress. Easy. Unfortunately, when you put it like that, it looks a bit like a sweeping oversimplification, doesn't it? Hmm.

On the other hand, if you're not looking to demedicalize mental illness, why throw out the word illness?

The problem is that many people like the sound of demedicalization, but they're not sure how far they want to go. And in large organizations, some people will want to go much further than others.

Mental health charities seem to be particularly prone to this, so you often see them assuring people that "mental illness is an illness like any other", while simultaneously saying that seeing it just as a medical illness is far too narrow and unhelpful!

This is a serious debate, and it deserves a careful discussion. The compromise term "mental distress" seems to bridge this gap, and allows people with very different views to sound like they're agreeing with each other. This is not the best way to resolve debates like this. People still disagree with each other. They just lack the words to talk about it.

Britain's Not Getting More Mentally Ill

There's a widespread belief that mental illness is getting more common, or that it has got more common in recent years.

A new study in the British Journal of Psychiatry says: no, it's not. They looked at the UK APMS mental health surveys, which were done in 1993, 2000 and 2007. Long-time readers will remember these.

The authors of the new paper analyzed the data by birth cohort, i.e. when you were born, and by age at the time of the survey. If mental illness were rising, you'd predict that people born more recently would have higher rates of mental illness at any given age.

The headline finding: there was no cohort effect, implying that rates of mental illness aren't changing. There was a strong age effect: in men, rates peak at about age 50; in women the data is rather messy but in general the rate is flat up to age 50 and then it falls off, like in men. But there's no evidence that those born recently are at higher risk.

The only exception was that men born after 1950 were at somewhat higher risk than those born earlier as shown by the "break" on the graph above. The effect for women was smaller. The most recent cohort, those born after 1985, were also above the curve but there was only one datapoint there, so it's hard to interpret.

We also get a rather cute graph showing how life changes with age:

As you get older, you get less irritable and, if you're a woman, you'll worry less. But sleep problems and, in men, fatigue, increase. Overall, 50 is the worst age in terms of total symptoms. After that, it gets better. Well, that's nice to know. Or not, depending on your age.

Overall, the authors say:

Our finding of subsequently stable rates contradicts popular media stories of a relentlessly rising tide of mental illness, at least for men. Stable prevalence in the male population, together with peaking of the prevalence of common mental disorder at about age 50 years, indicates that a large increase in projected rates of poor mental health is unlikely in the male population in the near future....

Trends in women are less clearly identified, with considerable increases in the prevalence of sleep problems, but no clear increase or even some decrease in other measures. Further research is needed to relate these age and cohort differences to drivers of mental health such as employment status and family composition.

Caution's warranted, though, because the APMS data were based on self-reported symptoms of mental illness assessed by lay interviewers. As I've argued before, self-report is problematic, but this is true of almost all of these kinds of studies.

More unusual is that this study didn't attempt to assign formal diagnoses, it just looked at total symptoms on the CIS Scale; a total of 12 or more was considered to indicate "probable disorder".

Purists would say that this is a weakness and that you ought to be making full DSM-IV diagnoses, but honestly, it's got its own problems, and I think this is no worse.

Finally, this study only looked at "common mental disorders" i.e. depression and various kinds of anxiety symptoms. Things like schizophrenia and bipolar disorder weren't included, but from what I remember they're not rising either.

Spiers N, Bebbington P, McManus S, Brugha TS, Jenkins R, & Meltzer H (2011). Age and birth cohort differences in the prevalence of common mental disorder in England: National Psychiatric Morbidity Surveys 1993-2007. The British journal of psychiatry : the journal of mental science, 198, 479-84 PMID: 21628710

Britain's Not Getting More Mentally Ill

There's a widespread belief that mental illness is getting more common, or that it has got more common in recent years.

A new study in the British Journal of Psychiatry says: no, it's not. They looked at the UK APMS mental health surveys, which were done in 1993, 2000 and 2007. Long-time readers will remember these.

The authors of the new paper analyzed the data by birth cohort, i.e. when you were born, and by age at the time of the survey. If mental illness were rising, you'd predict that people born more recently would have higher rates of mental illness at any given age.

The headline finding: there was no cohort effect, implying that rates of mental illness aren't changing. There was a strong age effect: in men, rates peak at about age 50; in women the data is rather messy but in general the rate is flat up to age 50 and then it falls off, like in men. But there's no evidence that those born recently are at higher risk.

The only exception was that men born after 1950 were at somewhat higher risk than those born earlier as shown by the "break" on the graph above. The effect for women was smaller. The most recent cohort, those born after 1985, were also above the curve but there was only one datapoint there, so it's hard to interpret.

We also get a rather cute graph showing how life changes with age:

As you get older, you get less irritable and, if you're a woman, you'll worry less. But sleep problems and, in men, fatigue, increase. Overall, 50 is the worst age in terms of total symptoms. After that, it gets better. Well, that's nice to know. Or not, depending on your age.

Overall, the authors say:

Our finding of subsequently stable rates contradicts popular media stories of a relentlessly rising tide of mental illness, at least for men. Stable prevalence in the male population, together with peaking of the prevalence of common mental disorder at about age 50 years, indicates that a large increase in projected rates of poor mental health is unlikely in the male population in the near future....

Trends in women are less clearly identified, with considerable increases in the prevalence of sleep problems, but no clear increase or even some decrease in other measures. Further research is needed to relate these age and cohort differences to drivers of mental health such as employment status and family composition.

Caution's warranted, though, because the APMS data were based on self-reported symptoms of mental illness assessed by lay interviewers. As I've argued before, self-report is problematic, but this is true of almost all of these kinds of studies.

More unusual is that this study didn't attempt to assign formal diagnoses, it just looked at total symptoms on the CIS Scale; a total of 12 or more was considered to indicate "probable disorder".

Purists would say that this is a weakness and that you ought to be making full DSM-IV diagnoses, but honestly, it's got its own problems, and I think this is no worse.

Finally, this study only looked at "common mental disorders" i.e. depression and various kinds of anxiety symptoms. Things like schizophrenia and bipolar disorder weren't included, but from what I remember they're not rising either.

Spiers N, Bebbington P, McManus S, Brugha TS, Jenkins R, & Meltzer H (2011). Age and birth cohort differences in the prevalence of common mental disorder in England: National Psychiatric Morbidity Surveys 1993-2007. The British journal of psychiatry : the journal of mental science, 198, 479-84 PMID: 21628710

Political Suicide

When is killing yourself not suicide?

In the British Journal of Psychiatry, two psychiatrists and an anthropologist discuss recent cases of self-immolation as a form of political protest in the Arab world:

Since ancient times there has been a difference between suicide (an act of self-destruction) and self-immolation which, although self- destructive, has a sacrificial connotation. Self-immolation is associated with terrible physical pain (burning alive) and with the idea of courage... It is, however, a new phenomenon in Arab Muslim societies.

The self-immolation of the young Tunisian Mohamed Bouazizi, a street vendor, expresses both the extreme hurt associated with the harassment and humiliation that was inflicted on him after his wares had been confiscated, and the fact that there were no other ways to be heard in a country where he knew no kind of political system other than dictatorship...His gesture is now being replicated, mostly by other young men in Arab countries.

These events ....raise important issues for psychiatrists and mental health professionals. First, these events highlight the social, political and cultural dimensions of suicide as a powerful collective idiom of distress. In the Tunisian case there is a shift from an individual sinful suicide to a sacrifice which evokes martyrdom. Fire symbolises purification...

Second, in spite of the fact that the idiom of distress put forward by these Arab youth is radically different from the usual profile of youth suicide in Western countries, these events may also be an invitation to rethink the collective dimensions of youth suicide as a protest against society. Without minimising the role of psychopathology and interpersonal factors, it may be time to revisit the collective meaning associated by youth with the decision to exit a world in which they may feel they do not always have a voice.

There's certainly a perception that some suicide is "political", and quite different from similar actions done for "personal" reasons. The same goes for breaking the law: we make a distinction between "common criminals", who do it for their own sake, and people who do so for an ideal.

But I wonder whether this political/personal distinction is so clear-cut, psychologically speaking. Even "political" suicide has a personal component: in most cases, millions of people are in the same political situation, but only a few people burn themselves. Politics alone doesn't explain any individual case.

Conversely the idea that "personal" suicide is simply a symptom of an individual's mental illness is likewise inadaquate - most people with mental illness, even very severe cases, do not do it. We have to look into the social sphere as well.

Emile Durkheim drew a distinction between "egoistic" suicide, related to an individual's "prolonged sense of not belonging, of not being integrated in a community" and "anomic" suicide, caused by upheavals in society leading to "an individual's moral confusion and lack of social direction". But aren't those different ways of looking at the same thing?

Cheikh IB, Rousseau C, & Mekki-Berrada A (2011). Suicide as protest against social suffering in the Arab world. The British journal of psychiatry : the journal of mental science, 198, 494-5 PMID: 21628715

Political Suicide

When is killing yourself not suicide?

In the British Journal of Psychiatry, two psychiatrists and an anthropologist discuss recent cases of self-immolation as a form of political protest in the Arab world:

Since ancient times there has been a difference between suicide (an act of self-destruction) and self-immolation which, although self- destructive, has a sacrificial connotation. Self-immolation is associated with terrible physical pain (burning alive) and with the idea of courage... It is, however, a new phenomenon in Arab Muslim societies.

The self-immolation of the young Tunisian Mohamed Bouazizi, a street vendor, expresses both the extreme hurt associated with the harassment and humiliation that was inflicted on him after his wares had been confiscated, and the fact that there were no other ways to be heard in a country where he knew no kind of political system other than dictatorship...His gesture is now being replicated, mostly by other young men in Arab countries.

These events ....raise important issues for psychiatrists and mental health professionals. First, these events highlight the social, political and cultural dimensions of suicide as a powerful collective idiom of distress. In the Tunisian case there is a shift from an individual sinful suicide to a sacrifice which evokes martyrdom. Fire symbolises purification...

Second, in spite of the fact that the idiom of distress put forward by these Arab youth is radically different from the usual profile of youth suicide in Western countries, these events may also be an invitation to rethink the collective dimensions of youth suicide as a protest against society. Without minimising the role of psychopathology and interpersonal factors, it may be time to revisit the collective meaning associated by youth with the decision to exit a world in which they may feel they do not always have a voice.

There's certainly a perception that some suicide is "political", and quite different from similar actions done for "personal" reasons. The same goes for breaking the law: we make a distinction between "common criminals", who do it for their own sake, and people who do so for an ideal.

But I wonder whether this political/personal distinction is so clear-cut, psychologically speaking. Even "political" suicide has a personal component: in most cases, millions of people are in the same political situation, but only a few people burn themselves. Politics alone doesn't explain any individual case.

Conversely the idea that "personal" suicide is simply a symptom of an individual's mental illness is likewise inadaquate - most people with mental illness, even very severe cases, do not do it. We have to look into the social sphere as well.

Emile Durkheim drew a distinction between "egoistic" suicide, related to an individual's "prolonged sense of not belonging, of not being integrated in a community" and "anomic" suicide, caused by upheavals in society leading to "an individual's moral confusion and lack of social direction". But aren't those different ways of looking at the same thing?

Cheikh IB, Rousseau C, & Mekki-Berrada A (2011). Suicide as protest against social suffering in the Arab world. The British journal of psychiatry : the journal of mental science, 198, 494-5 PMID: 21628715

Antivirals and Suicide

A case report from India describes a man who became suicidally depressed while being given drugs to treat a viral infection:

A 43-year-old man diagnosed with chronic hepatitis C viral infection ... was started on therapy with interferon -α-2a and ribavirin ... Screening tests for hepatitis B virus, hepatitis A virus, and HIV were negative.

In initial 3 months of start of therapy with IFN-α-2a and ribavirin, the patient experienced adverse effects in the form of high-grade fever, malaise, myalgia, and fatigue which were relieved by paracetamol. After 16 weeks of therapy, the patient reported to experience feeling of guilt, anxiety, fear, and sadness.

He wanted to keep himself isolated from family and friends. He started blaming himself for financial crises he was facing that time. He was unable to perform his job as school teacher. Hamilton Depression Rating Scale (HDRS-17) revealed the patient to be suffering from moderate to severe depression with score of 15.

He was given psychotherapy for the same. Paroxetine and zolpidem were started [but] he did not respond significantly to antidepressants over 3 weeks. After 25 days of starting antidepressants, the patient attempted suicide but was rescued in time.

IFN-α-2a and ribavirin were withheld for 1 month and antidepressants were continued. Patient's condition normalized and he started taking interest in self and surroundings. He started following his normal routine.

He was then put back on the drugs for 3 weeks, but he got depressed again. So treatment was aborted and he was back to feeling fine within a week.

Interferons are powerful antivirals but they have the dubious honor of being one of the few medical drugs clearly implicated in causing depression. Others include reserpine, an anti-hypertensive and rimonabant, a weight-loss drug (it got banned for this reason).

The anti-malarial mefloquine can cause a range of neuropsychiatric symptoms including depression but also hallucinations and nightmares, as can the HIV drug efavirenz which I covered recently.

Most people who take each of these drugs don't experience problems but in a non-trivial minority it happens. It obviously poses a serious problem for doctors, but it's also very interesting for people researching mood and depression. Work out why these drugs cause depression, and it might help work out why people get "normal" clinical depression.

For example, just recently it was shown that mefloquine has a unique and unusual effect on cells in the dopamine system of the brain, responsible for motivation and pleasure. Whether this explains the side-effects is an open question but without mefloquine we wouldn't even be able to ask it.

As for interferons, which are actually not drugs as such but rather molecules produced by the immune system during infections, it's given rise to the inflammation theory of depression. There's always a risk, though, that by focussing too much on just one class of depressing drug, you'll end up with a narrow theory that can't account for the others.

Inder D, Rehan HS, Yadav M, Manak S, & Kumar P (2011). IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report. Indian journal of pharmacology, 43 (2), 210-1 PMID: 21572662

Antivirals and Suicide

A case report from India describes a man who became suicidally depressed while being given drugs to treat a viral infection:

A 43-year-old man diagnosed with chronic hepatitis C viral infection ... was started on therapy with interferon -α-2a and ribavirin ... Screening tests for hepatitis B virus, hepatitis A virus, and HIV were negative.

In initial 3 months of start of therapy with IFN-α-2a and ribavirin, the patient experienced adverse effects in the form of high-grade fever, malaise, myalgia, and fatigue which were relieved by paracetamol. After 16 weeks of therapy, the patient reported to experience feeling of guilt, anxiety, fear, and sadness.

He wanted to keep himself isolated from family and friends. He started blaming himself for financial crises he was facing that time. He was unable to perform his job as school teacher. Hamilton Depression Rating Scale (HDRS-17) revealed the patient to be suffering from moderate to severe depression with score of 15.

He was given psychotherapy for the same. Paroxetine and zolpidem were started [but] he did not respond significantly to antidepressants over 3 weeks. After 25 days of starting antidepressants, the patient attempted suicide but was rescued in time.

IFN-α-2a and ribavirin were withheld for 1 month and antidepressants were continued. Patient's condition normalized and he started taking interest in self and surroundings. He started following his normal routine.

He was then put back on the drugs for 3 weeks, but he got depressed again. So treatment was aborted and he was back to feeling fine within a week.

Interferons are powerful antivirals but they have the dubious honor of being one of the few medical drugs clearly implicated in causing depression. Others include reserpine, an anti-hypertensive and rimonabant, a weight-loss drug (it got banned for this reason).

The anti-malarial mefloquine can cause a range of neuropsychiatric symptoms including depression but also hallucinations and nightmares, as can the HIV drug efavirenz which I covered recently.

Most people who take each of these drugs don't experience problems but in a non-trivial minority it happens. It obviously poses a serious problem for doctors, but it's also very interesting for people researching mood and depression. Work out why these drugs cause depression, and it might help work out why people get "normal" clinical depression.

For example, just recently it was shown that mefloquine has a unique and unusual effect on cells in the dopamine system of the brain, responsible for motivation and pleasure. Whether this explains the side-effects is an open question but without mefloquine we wouldn't even be able to ask it.

As for interferons, which are actually not drugs as such but rather molecules produced by the immune system during infections, it's given rise to the inflammation theory of depression. There's always a risk, though, that by focussing too much on just one class of depressing drug, you'll end up with a narrow theory that can't account for the others.

Inder D, Rehan HS, Yadav M, Manak S, & Kumar P (2011). IFN-α-2a (Interferon) and ribavirin induced suicidal attempt in a patient of chronic HCV: A rare case report. Indian journal of pharmacology, 43 (2), 210-1 PMID: 21572662

There's no DNA in "Disease"

Back when I was a mere first year biology student, the first thing we were taught was this:

DNA makes RNA makes Protein.

This is the Central Dogma of Molecular Biology, and it describes the intricate and beautiful process by which genes influence living things. The whole thing really is remarkable.

Unfortunately, some people in psychiatry seem to have forgotten this. Reading some of the literature, you would think that:

DNA makes DSM Diagnoses

Or if you're feeling especially adventurous and concious of the fact that diagnoses are not necessarily real entities

DNA makes Symptoms (which add up to make DSM Diagnoses)

In fact, DNA has nothing to do with symptoms either, not directly. DNA makes proteins. Proteins interact with each other, and with all kinds of hormones and other signalling molecules, to control the growth and function of cells. Cells don't get symptoms. People get symptoms - and people are very complex systems made of billions of cells.

So it would be extremely weird if a particular genetic variant only ever caused one specific disease. That would mean that, whenever you have that variant, and regardless of any other variants or environmental factors, it will always mess up cell function such that it causes the same ultimate symptoms.

That does happen. There are lots of single-gene disorders - or to put it another way, single-disorder genes. But they may well be the exception. Rather, as Matthew State says in a short paper just out in Biological Psychiatry, the latest research suggests that genes that are linked to one psychiatric disorder are usually linked to lots of them, sometimes ones with quite different symptoms.

I previously wrote about the case of "The ADHD Gene" that's actually a gene for lots of stuff including, sometimes, ADHD. State focusses on the example of the gene CNTNAP2, variants in which have been linked to (deep breath): epilepsy, mental retardation, autism, social anxiety, schizophrenia and Tourette's. Sometimes the same variant causes multiple different disorders in different people. Sometimes one variant causes one thing and protects against another, related, thing. Hmm.

As State says, one possibility is that any given mutation always causes the same symptoms, it's just that our diagnostic categories are imperfect so the same symptoms get labelled as many different things. That's certainly true but as he points out, there's a more radical possibility: the same variant might cause genuinely different symptoms.

mutations at single gene or locus may carry significant risks for truly divergent neurodevelopmental outcomes, neither demonstrating specificity for a clinically observable phenomenon nor conferring any reliable overlap among disparate behavioral phenotypes.

How? Well, suppose there was a variant, "pinker", that codes for a fluorescent protein that makes half of your brain cells glow bright pink. By itself, that wouldn't cause symptoms. No-one would even know.

Yet imagine another variant, "pinkophobe", that made cells refuse to communicate with pink cell. That wouldn't cause any symptoms either, by itself. But in conjunction with "pinker", where it would cause serious problems: half of your cells would be effectively out of action.

But suppose you carried "pinker" and yet another variant, "welovepink", that made your cells respond much more strongly to pink cells. Then, you would have the opposite problem. Half of your cells would be super-responsivie to the other half, and that would probably cause epilepsy, amongst other things. You'd get symptoms, but they would be completely different symptoms from people who had "pinker" and "pinkophobe".

So what symptoms does "pinker" cause? It doesn't cause symptoms. It's just a gene. The symptoms come much later. "pinker" would be associated with all kinds of stuff, even though it has a very specific role. It just codes for one protein. Genes are pretty simple folk. The complexity comes later.

This is a silly example, but maybe not so far fetched after all. Neurons don't glow pink, but they do release neurotransmitters, and they don't have color preferences, but they do have receptors that respond to transmitters.

State MW (2011). The Erosion of Phenotypic Specificity in Psychiatric Genetics: Emerging Lessons from CNTNAP2. Biological psychiatry, 69 (9), 816-7 PMID: 21497679

There's no DNA in "Disease"

Back when I was a mere first year biology student, the first thing we were taught was this:

DNA makes RNA makes Protein.

This is the Central Dogma of Molecular Biology, and it describes the intricate and beautiful process by which genes influence living things. The whole thing really is remarkable.

Unfortunately, some people in psychiatry seem to have forgotten this. Reading some of the literature, you would think that:

DNA makes DSM Diagnoses

Or if you're feeling especially adventurous and concious of the fact that diagnoses are not necessarily real entities

DNA makes Symptoms (which add up to make DSM Diagnoses)

In fact, DNA has nothing to do with symptoms either, not directly. DNA makes proteins. Proteins interact with each other, and with all kinds of hormones and other signalling molecules, to control the growth and function of cells. Cells don't get symptoms. People get symptoms - and people are very complex systems made of billions of cells.

So it would be extremely weird if a particular genetic variant only ever caused one specific disease. That would mean that, whenever you have that variant, and regardless of any other variants or environmental factors, it will always mess up cell function such that it causes the same ultimate symptoms.

That does happen. There are lots of single-gene disorders - or to put it another way, single-disorder genes. But they may well be the exception. Rather, as Matthew State says in a short paper just out in Biological Psychiatry, the latest research suggests that genes that are linked to one psychiatric disorder are usually linked to lots of them, sometimes ones with quite different symptoms.

I previously wrote about the case of "The ADHD Gene" that's actually a gene for lots of stuff including, sometimes, ADHD. State focusses on the example of the gene CNTNAP2, variants in which have been linked to (deep breath): epilepsy, mental retardation, autism, social anxiety, schizophrenia and Tourette's. Sometimes the same variant causes multiple different disorders in different people. Sometimes one variant causes one thing and protects against another, related, thing. Hmm.

As State says, one possibility is that any given mutation always causes the same symptoms, it's just that our diagnostic categories are imperfect so the same symptoms get labelled as many different things. That's certainly true but as he points out, there's a more radical possibility: the same variant might cause genuinely different symptoms.

mutations at single gene or locus may carry significant risks for truly divergent neurodevelopmental outcomes, neither demonstrating specificity for a clinically observable phenomenon nor conferring any reliable overlap among disparate behavioral phenotypes.

How? Well, suppose there was a variant, "pinker", that codes for a fluorescent protein that makes half of your brain cells glow bright pink. By itself, that wouldn't cause symptoms. No-one would even know.

Yet imagine another variant, "pinkophobe", that made cells refuse to communicate with pink cell. That wouldn't cause any symptoms either, by itself. But in conjunction with "pinker", where it would cause serious problems: half of your cells would be effectively out of action.

But suppose you carried "pinker" and yet another variant, "welovepink", that made your cells respond much more strongly to pink cells. Then, you would have the opposite problem. Half of your cells would be super-responsivie to the other half, and that would probably cause epilepsy, amongst other things. You'd get symptoms, but they would be completely different symptoms from people who had "pinker" and "pinkophobe".

So what symptoms does "pinker" cause? It doesn't cause symptoms. It's just a gene. The symptoms come much later. "pinker" would be associated with all kinds of stuff, even though it has a very specific role. It just codes for one protein. Genes are pretty simple folk. The complexity comes later.

This is a silly example, but maybe not so far fetched after all. Neurons don't glow pink, but they do release neurotransmitters, and they don't have color preferences, but they do have receptors that respond to transmitters.

State MW (2011). The Erosion of Phenotypic Specificity in Psychiatric Genetics: Emerging Lessons from CNTNAP2. Biological psychiatry, 69 (9), 816-7 PMID: 21497679

Revenge Of The Depression Gene

Last year, the world of psychiatric genetics was rocked by the news that a highly-studied gene, believed to be associated with depression, wasn't in fact linked to depression at all.

The genetic variant was 5-HTTLPR. It's a length variant in the gene coding for the serotonin transporter protein (5HTT) which the target of antidepressants like Prozac. There are two flavors of this variant, short and long.

Many studies have shown that the short ("s") variant is associated with a high risk of getting depression in response to stress - but then last year a large meta-analysis of all the evidence concluded that there was in reality no link. Bummer.

Now another team of researchers have done a new analysis of the 5-HTTLPR & stress & depression data and they claim that there is a link after all: hooray! So who's right? I'm not sure, but the new paper raises many questions.

The new paper puts together the results of all 54 studies which have looked at this gene in the context of depression, caused by any kind of stress. The authors were intentionally liberal in their inclusion criteria: studies in any population were OK, for example they included people with Parkinson's disease or heart disease.

They say that this is the main difference between the present work and earlier meta-analyses that found no link. The famous 2010 paper, for example, only included 14 studies because they only considered certain kinds of stress.

Anyway, the short variant is associated with depression after all, across all of the studies. They extracted the p values from the results of all previous studies, and took the average of those, weighted by the sample size. They found a very significant association: P=.00002.

Here's all the results. Each square is a study, the further to the left, the more strongly they found an association. Bigger squares mean larger studies. As you can see, most studies found a link but the three largest studies - which were much larger than the others - found none. Hmm.

In terms of specific kinds of stress, they found strong evidence that "specific stressors" (like medical illness), and childhood trauma, were associated with more depression in s-allele carriers. However, in the studies on "Stressful Life Events", which is a broad category meaning pretty much anything bad that happens, the evidence was weaker. The previous meta-analyses only considered these studies.

Ultimately, I think this analysis should remind us that the issue of 5HTTLPR is still "open", but I have concerns about the dataset. The fact that larger studies seem less likely to be positive is a classic warning sign of publication bias.

The authors do consider this and say that they calculate that there would have to be over 700 unpublished, negative studies out there, in order to make the overall data negative. They also find that you could ignore the smallest 45 studies and still find a result. But still. Something doesn't feel right. Maybe I just have the wrong 5HTTLPR variant.

Karg K, Burmeister M, Shedden K, & Sen S (2011). The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited: Evidence of Genetic Moderation. Archives of general psychiatry, 68 (5), 444-54 PMID: 21199959