The Stigma(s) of Mental Illness

Fighting "the stigma of mental illness" is big business at the moment. But does "the stigma" really exist?

As I said back in 2010 :

There is a stigma of schizophrenia, and there's a stigma of depression, etc. but they're not the same stigma. We're told it's a myth that "the mentally ill are violent" - [but] no-one thinks depressed or anorexic people are violent. They think (roughly) that people with psychosis are. They have other equally silly opinions about each diagnosis, but there's no monolithic "stigma of mental illness".

Now a paper has come out which explores this idea in some detail: Stereotypes of mental disorders differ in competence and warmth. The title says it all : people have stereotypical views of people suffering from different mental disorders, but these stereotypes vary substantially.

The authors use the "Stereotype Content Model" framework, which despite the fancy name is very simple. On this view stereotypes are characterised by two dimensions, "competence" and "warmth". These are pretty self-explanatory. Warmth is whether you're seen as nice and friendly, or hostile and dangerous. Competence is whether you're thought to be good at it.

We all know that warmth and competence are distinct and indeed orthogonal concepts, and they crop up in other languages and in popular culture.

Anyway, in two Mechanical Turk online surveys of American adults, they first showed that respondants felt that "people with mental illness" were low on competence and (slightly) low on warmth, compared to other social and ethnic groups. That's similar to the ratings of the homeless, poor, and welfare recipients.

However in the second study, they asked about specific diagnoses, and this revealed a more complex pattern. I've shown the results above (colors are mine). There seemed to be four clusters. Mental retardation and Alzheimer's were perceived as warm, but incompetent; sociopaths and violent criminals were the opposite.

Schizophrenia clustered with homelessness and addiction in a worst-of-both-worlds category of low warmth and competence, while what could broadly be called "emotional" disorders, like bipolar, depression and anxiety, were rated more favorably. For what its worth, OCD was the least bad diagnosis.

These are interesting results. The only oddity about the method was that people weren't actually asked what they thought about these people; they were asked “In general, how much do Americans believe that..." This is, apparantly, standard procedure in this kind of stereotype research, but it seems a little strange to me.

Sadler, M., Meagor, E., and Kaye, K. (2012). Stereotypes of mental disorders differ in competence and warmth Social Science and Medicine DOI: 10.1016/j.socscimed.2011.12.019

Good Science, Bad History, in the British Journal of Psychiatry

The latest February 2012 issue of the British Journal of Psychiatry features a paper about the association between child abuse and later mental health problems. I haven't read it yet, but it looks pretty good.

However, it also includes an editorial from John Read and Richard Bentall which argues that:

Just 20 years ago, however, it would have been difficult to get the paper published. Mental health professions have been slow, even resistant, to recognise the role of childhood adversities in psychiatric disorder... Until very recently the hypothesis that abuse in childhood has a causal role in psychosis was regarded by many biologically oriented psychiatrists as heresy...

Really? I checked the BJP from exactly 20 years ago. The February 1992 issue contained:

• A paper about child sexual abuse in female psychiatric patients.
• A letter praising a different article, on the same topic.
• A review of 11 studies on psychosocial family interventions as treatments for schizophrenia.
• A paper looking at the effect of the social environment on symptoms of schizophrenia.

Four strikes and they're out. It's not true that this kind of thing wasn't being discussed 20 years ago.

Such grandstanding is bad for science. Few would deny that psychiatry in recent years has undervalued psychosocial factors and overvalued genetics and neuroscience, but it's actually quite a complicated story, not a Punch and Judy show with bad guys on one side and good guys on the other.

Rhetorical flourishes like this editorial certainly get attention but in the long run, down that road lies madness.

Read, J., and Bentall, R. (2012). Negative childhood experiences and mental health: theoretical, clinical and primary prevention implications The British Journal of Psychiatry, 200 (2), 89-91 DOI: 10.1192/bjp.bp.111.096727

Science Majors are from Mars...

According to a new study, students with a family history of autism tend to major in math and science, while substance abuse and depression are more common in the ancestors of humanities fans.

In an online survey, over 1,000 new Princeton undergrads were asked about their intended major and whether anyone in their family had been diagnosed with one of 16 neurological and psychiatric disorders. More details here.

Of the 16 maladies, 5 were so rare that there wasn't enough data to analyze. Of the remaining 11, there were significant differences between the three types of students in four. The categories being humanities, social sciences, and "technical" i.e. science, engineering and maths. Social science majors were in the middle, except for autism.

See the graph I made above.

It's an interesting study. The autism result seems tenuous though because only 24 of 1077 students reported any autism in their immediate family. That's 3% of "technical" students and 1% of others, so not very many. The authors excluded schizophrenia and epilepsy from the analysis on the grounds of being too rare - and they had 18 each. Substance abuse and depression had over 150 each, so those differences are rather more solid.

The authors note that this fits with various previous studies and they discuss their findings in Baron-Cohen-esque terms:

It has been suggested that autism represents an extreme manifestation of a ‘‘systemizing’’ nature. Since ASDs have complex inheritance, shared genetic variation between close relatives might establish a continuous phenotype which in milder forms confers interest or benefits in understanding highly structured fields... Similarly, affective disorders may represent an extreme phenotype of emotional lability that, in milder forms, is commensurate with interest in the humanities.

Hmm. OK, but does that really make sense? Sure, it fits with the popular image of the Geeky Scientist vs the Tortured Artist - but that's not science, that's stereotypes. Why would emotional lability make you favor the humanities, exactly?

Imagine if the stereotype was the Geeky Artist vs the Tortured Scientist (and there really have been plenty of both, over the years). Couldn't we rationalize that equally well? Picture the scene... -

"People with autistic traits are drawn to study the humanities because they wish to learn about humans and their emotions, something they find hard to do in day-to-day life... While emotionally volatile people like science and maths because they offer a calming sense of order and stability..."

Campbell BC, and Wang SS (2012). Familial Linkage between Neuropsychiatric Disorders and Intellectual Interests. PloS one, 7 (1) PMID: 22291951

Young, Canadian and on Antipsychotics

Antipsychotic use in Canadian children and teens is rising dramatically - prescriptions more than doubled in just 4 years, from 2005 to 2009.

That's according to a paper just out from Pringsheim et al. It's been known for a while that broadly the same is true of the USA. The data reveal that the Canadian border is no barrier to the spread of antipsychotics.

What's surprising is that while in the USA, some of these drugs are officially licensed for use in certain children and adolescent psychiatric disorders, in Canada all such use is off-label. That didn't stop there being nearly 700,000 youth prescriptions for an antipsychotic in 2009, in a country with a total population of 35 million - although bear in mind that this includes multiple prescriptions for the same person.

The growth in antipsychotics is accounted for by the second-generation "atypical" antipsychotics. Risperidone (Risperdal) was the biggest success story accounting for well over half of the total.


What's disturbing about this, as I've said before, is not so much the fact that these drugs are being used but the speed of the growth. It represents a fundamental shift in the way children and adolescent mental health problems are treated, one which has happened so fast that it's hard to believe that there was time to properly think through the consequences...

Use of SSRI antidepressants and psychostimulants (mainly ADHD drug methylphenidate, Ritalin) also rose between 05 and 09, but only by about 40%. That means that there were more antipsychotic than SSRI prescriptions in children and teens by 09, which is pretty remarkable.

Only 13% of the youth antipsychotic recommendations were actually for psychosis, the original indication of the drugs. The leading diagnosis was ADHD, which is odd, because the main drugs for ADHD, such as Ritalin, boost dopamine release, while antipsychotics block dopamine's effects via D2 receptors.


Other popular indications were mood disorders and conduct disorders. Overall, the fact that the vast majority of the antipsychotic prescriptions were not for psychosis confirms the view that the term "antipsychotic" for these drugs is misleading.

Pringsheim T, Lam D, and Patten SB (2011). The Pharmacoepidemiology of Antipsychotic Medications for Canadian Children and Adolescents: 2005-2009. Journal of child and adolescent psychopharmacology PMID: 22136092

A Psychedelic Tale of Two Neurotransmitters

An unexpected interaction between neurotransmitter systems may explain psychosis and hallucinations, according to a fascinating new paper.

Serotonin (5HT) and glutamate are two neurotransmitters. Up until now, it was thought that they acted independently. A given neuron might have receptors for both serotonin and glutamate, but they didn't interact: serotonin would never affect the glutamate receptors, and vice versa.

The new research overturns that view. Authors Miguel Fribourg and colleagues of Mount Sinai School of Medicine show, in a series of elegant experiments in mice, that different receptors can cluster together, forming a complex. The two receptors, serotonin's 5HT2A and glutamate's mGluR2, can talk to each other.

However, this doesn't seem to happen under normal conditions. Serotonin and glutamate don't seem to trigger the receptor interaction, or at least not very much. Only certain drugs can do it. And this is where it gets really interesting.

Psychedelic drugs, like LSD, have long been thought of as 5HT2A agonists, binding to the receptor and activating it. It turns out that this was only half right. They also inhibit mGluR2 transmission via the receptor complex. Serotonin itself is a 5HT2A agonist, but it doesn't do that. So psychedelics seem to be a kind of (for want of a better word) "superagonist".

It also works in reverse. The antipsychotic drugs clozapine and risperidone are known as 5HT2A antagonists. But Fribourg et al show that they also activate the mGluR2 receptor.

And the cross-talk can go in the other direction. Certain molecules that act on mGluR2 can either inhibit or promote 5HT2A. Unlike psychedelics and antipsychotics, these mGluR2 drugs have not been tested in humans yet. But these data predict that they will have psychedelic-like or antipsychotic-like effects, depending which way they work.

The interaction turns out to be all about G proteins, which are part of the chain of transmitter substances that convey signals within the cell, in response to neurotransmitters outside it. Here's a chart showing the effects of various drugs on the balance between different G proteins: the LSD-like psychedelic DOI has the opposite effect from the antipsychotics clozapine and risperidone.

This paper builds on a previous one from the same team showing that psychedelic 5HT2A "agonists" (like LSD and DOI) have different effects on G proteins from other, non-psychedelic agonists. That was interesting in itself but by adding glutamate to the picture, this new paper is really ground-breaking.

This goes a long way to explaining one of the mysteries of serotonin which is this:  if 5HT2A agonists like LSD are psychedelic, why aren't antidepressants the same? Almost all antidepressants work by increasing extracellular 5HT levels. That ought to mean that they activate 5HT2A receptors (indirectly). This explains why not - 5HT alone doesn't promote the crucial 5HT2A-mGluR2 interaction.

Taken together, these interesting results show clearly that 5HT2A and mGluR2 are hooking up and doing something exciting. Certainly in terms of how hallucinogens work.

I'm less convinced that this can directly explain antipsychotic effects though. The problem is that while newer "atypical" antipsychotics act on 5HT2A, the older antipsychotics don't, and atypicals are at best only slightly more effective on average.

What we don't yet know is whether this kind of complex receptor interactions can happen with other receptors. I'd have thought it unlikely that these two receptors were the only ones that could ever do it. The synapse looks like it's more complex than we could have imagined.

Fribourg M, et al. (2011). Decoding the Signaling of a GPCR Heteromeric Complex Reveals a Unifying Mechanism of Action of Antipsychotic Drugs. Cell, 147 (5), 1011-23 PMID: 22118459

Susan Greenfield's Dopamine Disaster

It's Susan Greenfield again.

Continuing her campaign warning of the dangers of modern technology in terms of their effects on the vulnerable brains of the young, the British neuroscientist and Baroness has written another article. This is the latest of many. None of them have been in peer reviewed academic journals.

This one's behind the Great Times Paywall so I can't link to it, but it's called Are video games taking away our identities?

The first part of the article is hard to argue against. Either you'll agree with it or you won't. Personally, videogames as Greenfield describes them bear little resemblance to any games that I've played recently. Similarly for her account of the Internet. But maybe this rings true for some:

Screen images do not depend for their impact on seeing one thing in terms of anything else. Their premium lies invariably in their raw sensory content... we are perhaps heading towards a much weaker sense of identity by engaging in a world where we are the passive recipient of senses and where there is no fixed narrative of past and future but an atomised thrill of the moment. One could even suggest that the constant self-centred readout on Twitter belies a more childlike insecurity, an existential crisis.

Greenfield then moves into discussing the brain, and this is where the science comes in. This is her "home turf" - she's Professor of physiology at Oxford. Yet it's a shambles.

There is one alarm bell ringing, which suggests that increasing 2D screen existence may be having undesirable effects: it is the threefold increase over the past decade in prescriptions for drugs for attention deficit hyperactivity disorder.

While this could be due to changes in doctors’ prescribing procedures, or indeed to a greater recognition and medicalisation of attentional problems, a third possibility could indeed be that if the young brain is exposed from the outset to a world of fast action-reaction, of instant new screen images flashing up with each press of a key, then such rapid interchange might lead to a shorter attention span.

The human condition can be basically divided into two alternating modes, first described by Euripedes... the rational “bread force”, characterised by a strong cognitive take on the world — a personalised past, present and future, in turn related to an active prefrontal cortex and lower levels of the brain chemical dopamine; and the “wine force”, more the state of young children or those adults indulging in “letting themselves go”, in situations perhaps involving wine, women and song, where a strong sensory environment demands less reflection, more passive reaction.

...An increase in physiological arousal can be linked to excessive release of dopamine. Could the screen experience be tilting this ancient balance in favour of the more infantile, senses-driven brain state?

Greenfield says that high dopamine and low prefrontal cortex activity is associated with irrationality and a deficit in attention. Video games are causing a flood of dopamine and causing ADHD. That would make sense, if ADHD was caused by too much dopamine, and if drugs for ADHD reduced dopamine release.

The problem is that it's the exact opposite. Drugs for ADHD increase dopamine release and ADHD is widely believed (although it's controversial) to be caused by a dopamine deficit.

Greenfield then says "We know too that dopamine suppresses the activity of neurons in the prefrontal cortex", but this is a serious oversimplification. Dopamine has complex effects on target neurons. It can inhibit firing, but it can also excite it. It all depends on the conditions. Here's what the authors of an influential scientific review said in 2004: "It is agreed by most researchers is that dopamine is a neuromodulator and is clearly not an excitatory or inhibitory neurotransmitter"

Some say that dopamine helps to "tune" the prefrontal by increasing the signal to noise ratio - more signal, less noise. Here's one of the most cited papers about dopamine and the PFC: Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.

Remember that drugs for ADHD like Ritalin, which are sometimes used illicitly by students without that disorder to help them focus and concentrate, cause dopamine release. If Greenfield were right, it would be the exact opposite.

...[other] people characterised by an underactive prefrontal cortex are those with schizophrenia, this time not due to physical damage but rather a chemical imbalance, in particular an excessive amount of the transmitter dopamine. In schizophrenia, like children, the patient is easily distracted, cannot interpret proverbs, is not strong on metaphor but takes the world literally; it is a vibrant world that can implode on, and overwhelm, the fragile firewall of the schizophrenic mindset.

This again is a serious simplification. Actually, you don't need to be a neuroscientist to work that out. Just recall the earlier bit: Greenfield has said that ADHD is caused by too much dopamine leading to an underactive prefrontal cortex. Now she says that schizophrenia is the same. So why are the symptoms of ADHD completely different from schizophrenia?

Why is it, in fact, that Ritalin and similar dopamine releasing drugs help with ADHD, but can make schizophrenia worse?

As a neuroscientist, I can tell you that we don't really know what's going on with dopamine in ADHD or schizophrenia. There's decent evidence that dopamine is involved in schizophrenia, but not in any straightforward sense. Schizophrenia is now believed to be linked to reduced dopamine in the prefrontal cortex, and too much in other areas.

As for ADHD, remember: the leading theory is that it's about too little dopamine. Not too much.

The only disease that we know certainly is associated with too little dopamine is Parkinson's. Contrary to Greenfield's theory, people with Parkinson's often have cognitive and mood problems as well as the better known difficulties with movements. They're not super intelligent, prefrontal-cortex-wielding geniuses.

I appreciate that an opinion piece in the Times is never going to be a rigorously argued scientific paper, but the fact that Greenfield's article contains several claims which are the exact opposite of the truth (or at least of current scientific thinking) calls her credibility into serious question.

Mountains of Mental Disorders

This is a story about a man who lived in a house. Here it is:

The house was a lovely thatched cabin, situated in a wooded valley between two little hills, set against the spectacular scenary of a snow-capped mountain. He'd been born there, and he'd lived there all his life.

One day, there was a knock on the man's door. He opened it to find two official-looking people carrying clipboards, with serious expressions on their faces.

"Hello, sir. We are officials from the Ministry of Mountains. Sorry it took us so long."
"Oh... excuse me?", the man replied, puzzled.
"We're very sorry we didn't get here earlier."
"I'm afraid that I don't know what you mean. I wasn't expecting any..."
"Hmm. Let me explain. The Ministry of Mountains exists to help people who live on mountains. So, you see, we're here to..."
"Ask for directions to the mountain? It's about 10 miles down the road. Just look up - you can't miss it."

The official looked unamused.
"No. We're here to help you, sir."
"Help you to cope with the rigors of mountain living!" the other chimed in, helpfully.
"But... I don't live on a mountain."
"I'm afraid you do. Look - " and the first official unfolded a large map. "Do you agree that there is a mountain, here?" and she pointed to a spot 10 miles down the road.
"Yes. Actually I just told you about i..."
"...and, do you agree that you live - here?"
"Of course, but..."

"So you do live on the mountain. The very ground beneath our feet right now is part of that mountain nearby."
"No it's not." The man protested. "This is a valley, miles away. I mean just look outside. We're clearly not on a mountain now, are we?"
"How old fashioned. That's what we used to think. But, thanks to advances in geology, we now appreciate that these hills and valleys are merely a part of the mountain."
"Yes!" the other said, whipping out a textbook and becoming increasingly enthusiastic. "You see, a mountain is merely a mass of rock, and this rock extends underground for a considerable distance... It's impossible, really, to draw a line on the map and say categorically, this side is mountain, this isn't. So 'mountains' are an arbitrary construct. 'Hills' are likewise just protrusions of the underlying mountain and..."

The man was even more confused now. "Umm... well, I suppose, technically...but..."
"...so yes, so you do live on a mountain. And we know that this is very difficult. You're exposed to all kinds of dangers like blizzards, altitude sickness, avalanches..."
"Not really. It's nice here. It doesn't even snow most years."
"That's unlikely. You agree that mountains have blizzards and avalanches? Right. And you earlier agreed that there's no dividing line between you and a mountain. So logically..."
"Er..."
"So you are in danger! Don't worry, though. We're here to help. To start off with, we're going to reinforce your house with six tons of cement, to protect you against rockfalls. The construction crew will arrive tomorrow morning. Now, as for those blizzards..."
The man had had enough of this.
"This is absurd. Now look - there is a guy who really does live on top of the mountain in a rickety old shack. Old Grandpa McHermit. He might actually need your help. I don't. Get out! And if I see anyone with a bag of cement tomorrow morning, I'll shove it right up their..."

---

As you may have guess, this story is a metaphor. There is a movement in psychiatry at the moment, away from a 'categorical' view of mental illness towards a 'spectrum' view. Mental disorders are not things you either have or don't - defined according to some arbitrary cut-off. Rather, they're things that everyone has, to some degree.

This has already happened, or is happening, to autism, schizophrenia, bipolar disorder, personality disorders, and more.

Now, the "spectrum" or "dimensional" approach has much to recommend it. It's true that diagnostic cutoffs are arbitrary. It's true that the categorical approach doesn't capture the true degree of variation that real people display.

My worry is that these new "spectra" are, in practice, merely the old categories, just bigger. We still think of people as being ill or not-ill, although we may call it on the spectrum or off it. Worse, we still think of "ill" in the same way as we used to i.e. as referring to the most severe end of the spectrum. The only difference is that we've expanded the old category of "ill" to cover more people.

This is evident in the fact that we still use the old categorical labels. It's the autism (or schizophrenia or bipolar) spectrum, even though "autism", in the old sense of a discrete disorder, is now supposed to be just one extreme of that spectrum. Yet the point about an extreme is that it's unusual, so why call it that?

We don't call the rainbow the red spectrum. We don't call height the midget spectrum. We don't call hills part of the mountain spectrum.

The point is, we really think of color and height and altitude as spectra, not as approximations to an extreme point, and that's good, because they are. Now it might well be possible to think of autistic or bipolar traits in the same way - but not if we call them autistic and bipolar traits. And not if we just rename them, while keeping the mental associations the same.

Not unless we can find a way of referring to what's currently called the autism spectrum without making anyone think of autism when they hear it. Similarly for "bipolar" and all the rest. Until we get to that point, there's a real risk that "spectra" will just be big categories.

Edit: This post has been very kindly translated into Hebrew over at the alhasapa.com blog.

Mental Illness And Creativity Revisited

A new study offers support for the theory that mental illness is associated with "creative" achievement.

The idea that madness is close to creative genius is a popular one. From the nutty professor to the tortured genius, there's no end of sterotypes, and pop culture seemingly offers plenty of examples, from Van Gogh and his ear to Charlie Sheen and his bi-winning.

But is it true?

A new study says yes. Kyaga et al looked at everyone in Sweden who had been treated as an inpatient for either schizophrenia, bipolar disorder, or depression, between 1973 and 2003. In total that meant about 300,000 people (two thirds of that was depression).

They then matched this up with the Swedish national census which asks people their occupation. They looked to see whether the psychiatric cases were more likely to have been employed in a "creative" profession. They defined that as visual artists (photographers, designers, etc.) non-visual artists (musicians, actors, authors) and academics (university teachers).

Finally, they pulled up the records on the patients' relatives, to see what their jobs were. This is one of those studies that could only happen in Scandinavia, because only those countries keep such comprehensive ( rather scarily so) info about their citizens.

They found that being bipolar, or being a close relative of someone who's bipolar, was associated with having a creative job. For schizophrenia, the picture was more complex: being a schizophrenia inpatient was not linked to being a creative in itself, but being related to someone with schizophrenia was. The effects were fairly modest.

For depression (not bipolar, just plain unipolar depression), there was no link at all, or even a slightly lower level.

The correlation wasn't driven by differences in IQ (yes, they had data on that too, for males, thanks to military service records.) Creative types had higher IQs on average while psych inpatients had slightly lower IQs than others. So correcting for IQ made the associations even stronger.

So it looks as though being bipolar, at any rate, is linked to creativity, and so is having bipolar and schizophrenia in the family - if you believe these findings. Should we?

This study was huge and the data are, on the face of it, very comprehensive. However, it turns out that many people didn't state their occupation, especially the patients. Only 45% of people with schizophrenia gave a valid answer, compared to 75% of the bipolar and depressed. In the controls, it was about 80%.

That's a serious issue. The authors did try to get around this by looking at the siblings of the patients with missing data. For schizophrenia, siblings of missing data schizophrenics were more creative than for the ones with full data, and for bipolar there was no difference. So the effects are not due to nonreporting of non-creative jobs.

Another possible confound is family background and environment. Indeed, the fact that people with bipolar were no more likely to be in a creative job than their relatives who weren't bipolar (or, at least, never received inpatient treatment) rather supports this view. Maybe the relatives shared genes with the patients meaning that their creativity was associated with bipolar, but we can't know that.

One reassuring piece of evidence against the idea that these results were driven by a general correlation between psychiatric hospitalization and "middle class professions" is that there was no association with the "non-creative" job of accountancy and auditing (sorry accountants and auditors).

Overall, while this is an interesting study, and while I find the proposed link between mental illness and creativity plausible, we need more detailed research to ensure that the correlation isn't just a reflection of socioeconomic factors.

Kyaga, S., Lichtenstein, P., Boman, M., Hultman, C., Langstrom, N. Landen, M. (2011). Creativity and mental disorder: family study of 300 000 people with severe mental disorder The British Journal of Psychiatry DOI: 10.1192/bjp.bp.110.085316

Schizophrenia And The Developing World Revisited

A major international study threatens to overturn what we thought we knew about schizophrenia.

People with schizophrenia are more likely to get better if they live in poor countries: that's been known for about 25 years. In the 1980s, a series of pioneering World Health Organization (WHO) studies looked at the prognosis for people diagnosed with schizophrenia around the world.

All of the data showed that people in developed countries were less likely to recover than those from poorer areas.

This paradoxical finding sparked no end of debate. What is it about these countries that makes them a better place to get schizophrenia? Patients in richer countries tend to have access to more and "better" psychiatric care, the latest drugs, and so on. Does this mean that those treatments are useless - worse, harmful? That's been the interpretation of some people.

But is it true? Not always, says a new study, W-SOHO. It's out in the British Journal of Psychiatry.

The authors compared schizophrenia outcomes in 37 countries. They recruited outpatients who were starting, or changing, antipsychotic medication. They found that in terms of "clinical" remission - i.e. improvement in the delusions, hallucinations, and other symptoms of schizophrenia - people in the developing world did indeed fare better than those from rich countries.

Over a 3 year period, 80-85% of patients from East Asia, the Middle East, and Latin America who started off ill, showed clinical remission, compared to 60-65% in Europe. That's not new: it confirms what the old WHO data showed.

But the new study also looked at "functional" remission - essentially, being able to participate in society:

having good social functioning for a period of 6 months. Good social functioning included those participants who had: (a) a positive occupational/vocational status, i.e. paid or unpaid full- or part-time employment, being an active student in university or housewife; (b) independent living; and (c) active social interactions, i.e. having more than one social contact during the past 4 weeks or having a spouse or partner.

For functional remission, Northern Europe (e.g. the UK, France, Germany) was the best place to get sick, with 35% achieving it. Not a very high figure, but better than elsewhere: it was just 18% in the Middle East and 25% in East Asia, despite these areas having the highest chances of clinical remission. Latin America did pretty well, however, at 29%.

This is a very important finding if it's true. Is it solid?

First off, were Northern European patients just less ill to start with? Not really. They had the highest rates of suicide attempts. They tended to be older, and to have been diagnosed at a later age, which was correlated with worse functional remission. Regression analyses confirmed that region was a predictor of remission controlling for all the other variables.

However, Northern European patients did tend to have better function at baseline. They were more likely to be employed, living independently, and socially active when they entered the study. 63% were living independently which is much higher than anywhere else: it was 24% in Middle East and Latin America. 23% had a paid job compared to 17-19% in developing countries.


That's not a flaw in the study as such but it does suggest that the differences, whatever they are, are already in place before people get treated.

One concern I have is that the definition of "functional remission" may be North Europe-centric. "Living independently" is something we aspire to but in other places, with a strong tradition of the extended family household, the idea that it would be a bad thing for someone with schizophrenia to be living with their family might seem silly. If that means they'll be cared for and supported, what's wrong with it?

And in terms of paid employment, Northern Europe just has a stronger economy than most other places (erm... well, it did back in 2000 when these data were collected), so maybe it's no surprise that people with schizophrenia were more likely to have paid jobs.

In terms of the study itself, it was extremely large with over 17,000 patients enrolled. But here's the thing: this study was run by Lilly, the drug company who make olanzapine, an antipsychotic used in schizophrenia. Three of the authors on the paper are Lilly employees, and the lead author was a consultant for them. The study deliberately sampled lots of people taking olanzapine, presumably in order to find out whether they did better.

None of this necessarily means that the data aren't valid, but I'm just not sure I trust Lilly over the WHO.

Haro JM, Novick D, Bertsch J, Karagianis J, Dossenbach M, & Jones PB (2011). Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. The British journal of psychiatry : the journal of mental science, 199, 194-201 PMID: 21881098

New Mutations - New Eugenics?

True or false: you inherit your genes from your parents.





Mostly true, but not quite. In theory, you do indeed get half of your DNA from your mother and half from your father; but in practice, there's sometimes a third parent as well, random chance. Genes don't always get transmitted as they should: mutations occur.



As a result, it's not true that "genetic" always implies "inherited". A disease, for example, could be entirely genetic, and almost never inherited. Down's syndrome is the textbook example, but it's something of a special case and until recently, it was widely assumed that most disease risk genes were inherited.



Yet recent evidence suggests that many cases of neurological and psychiatric disorders are caused by uninherited, de novo mutation events. Here are two papers from the last few weeks about schizophrenia(1,2) - but the story looks similar for autism, intellectual disabilities, some forms of epilepsy, ADHD, and others. Indeed they're often the same mutations.



Biologically, a given mutation is what it is, whether it's de novo or inherited. But on a social and a psychological level, I think there are crucial differences, and in particular I think that if it turns out that de novo mutations are important in disease, we're going to see attempts to take these variants out of circulation - far more so than in the case of the very same genes, were they inherited.



The old eugenics movement was based on the idea that if we stop people with bad genes from breeding - by sterilization, voluntary or otherwise, say - we'll be able to eliminate diseases and other undesirable traits. This idea is now generally regarded as extremely unethical, but many of its opponents have shared with the eugenicists the belief that it could work.



But if de novo mutations are what cause the majority of disease, then this approach would be pointless. Sterilizing certain people, or encouraging the healthy ones to have more children, would never be able to eliminate the 'bad genes' because new ones are being created every generation, pretty much at random.



So the de novo paradigm ought to be welcomed by opponents of eugenics. It wasn't just morally wrong - it was biologically misguided too.



But hang on. This is the 21st century. We have in vitro fertilization (IVF), and you can analyze the genes of an IVF embryo before you decide to make it into a child. In the near future, we might be able to routinely sequence the genome of any unborn child shortly after conception.



From there, it would be a small step to allowing parents to decide not to have children with de novo mutations.



This would be, in its effects, a form of eugenics - in the sense that it would produce the effect that the old eugenicists wanted. No more 'bad' genes, or not nearly as many. Opinions will differ as to whether it's morally different. But I would have said that politically, it's a lot more likely to happen.



I can't see forced sterilization returning any time soon. But if you were expecting a baby and you knew that it was not just carrying your and your partner's DNA, but had also suffered a mutation - might you not want to avoid that?



Psychologically, it matters that it did not inherit the gene. It would be a big step to decide that your child should not inherit one of your own genes. Of course, some genes are obviously harmful, like one that raises the risk of cancer, but think about the grey areas - a gene for social anxiety, mild autistic symptoms, obesity, a personality trait.



You might well feel that carrying that gene is what makes you, you; and so it would be natural for your child to have it. You might decide that if it was good enough for you (and all your ancestors), it's good enough for your children. You might well resent the very idea that it's a 'bad' gene at all, as an attack on your own self-worth.



But none of that applies if it's a de novo mutation. Indeed, quite the opposite - all those same considerations would probably lead you to want your children to carry as close as possible to a carbon copy of your DNA, with no random changes. It was good enough for you.



My point is that I think there will be much more support for the idea of genetic screening against de novo mutations than against inherited genes. More people will want it, it will be more socially acceptable, and more widely used. I'm not saying this would be a good or a bad thing, just making a prediction. In the future, diseases and traits that are primarily caused by de novo mutations will increasingly selected against.