Neurology Center

The first direct evidence of a genetic link to attention-deficit hyperactivity disorder has been found, a study says.

Wow! That's the headline. What's the real story?

The research was published in The Lancet, and it's brought to you by Wilson et al from Cardiff University: Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder.

The authors looked at copy-number variations (CNVs) in 410 children with ADHD, compared to 1156 healthy controls. A CNV is simply a catch-all term for when a large chunk of DNA is either missing ("deletions") or repeated ("duplications"), compared to normal human DNA. CNVs are extremely common - we all have a handful - and recently there's been loads of interest in them as possible causes for psychiatric disorders.

What happened? Out of everyone with high quality data available, 15.6% of the ADHD kids had at least one large, rare CNV, compared to 7.5% of the controls. CNVs were especially common in children with ADHD who also suffered mental retardation (defined as having an IQ less than 70) - 36% of this group carried at least one CNV. However, the rate was still elevated in those with normal IQs (11%).

A CNV could occur anywhere in the genome, and obviously what it does depends on where it is - which genes are deleted, or duplicated. Some CNVs don't cause any problems, presumably because they don't disrupt any important stuff.

The ADHD variants were very likely to affect genes which had been previously linked to either autism, or schizophrenia. In fact, no less than 6 of the ADHD kids carried the same 16p13.11 duplication, which has been found in schizophrenic patients too.

So...what does this mean? Well, the news has been full of talking heads only too willing to tell us. Pop-psychologist Oliver James was on top form - by his standards - making a comment which was reasonably sensible, and only involved one error:

Only 57 out of the 366 children with ADHD had the genetic variant supposed to be a cause of the illness. That would suggest that other factors are the main cause in the vast majority of cases. Genes hardly explain at all why some kids have ADHD and not others.

Well, there was no single genetic variant, there were lots. Plus, unusual CNVs were also carried by 7% of controls, so the "extra" mutations presumably only account for 7-8%. James also accused The Lancet of "massive spin" in describing the findings. While you can see his point, given that James's own output nowadays consists mostly of a Guardian column in which he routinely over/misinterprets papers, this is a bit rich.

The authors say that

the findings allow us to refute the hypothesis that ADHD is purely a social construct, which has important clinical and social implications for affected children and their families.

But they've actually proven that "ADHD" is a social construct. Yes, they've found that certain genetic variants are correlated with certain symptoms. Now we know that, say, 16p13.11-duplication-syndrome is a disease, and that its symptoms include (but aren't limited to) attention deficit and hyperactivity. But that doesn't tell us anything about all the other kids who are currently diagnosed with "ADHD", the ones who don't have that mutation.

"ADHD" is evidently an umbrella term for many different diseases, of which 16p13.11-duplication-syndrome is one. One day, when we know the causes of all cases of attention deficit and hyperactivity symptoms, the term "ADHD" will become extinct. There'll just be "X-duplication-syndrome", "Y-deletion-syndrome" and (because it's not all about genes) "Z-exposure-syndrome".

When I say that "ADHD" is a social construct, I don't mean that people with ADHD aren't ill. "Cancer" is also a social construct, a catch-all term for hundreds of diseases. The diseases are all too real, but the concept "cancer" is not necessarily a helpful one. It leads people to talk about Finding The Cure for Cancer, for example, which will never happen. A lot of cancers are already curable. One day, they might all be curable. But they'll be different cures.

So the fact that some cases of "ADHD" are caused by large rare genetic mutations, doesn't prove that the other cases are genetic. They might or might not be - for one thing, this study only looked at large mutations, affecting at least 500,000 bases. Given that even a deletion or insertion of just one base in the wrong place could completely screw up a gene, these could be just the tip of the iceberg.

But the other problem with claiming that this study shows "a genetic basis for ADHD" is that the variants overlapped with the ones that have recently been linked to autism, and schizophrenia. In other words, these genes don't so much cause ADHD, as protect against all kinds of problems, if you have the right variants.

If you don't, you might get ADHD, but you might get something else, or nothing, depending on... we don't know. Other genes and the environment, presumably. But "7% of cases of ADHD associated with mutations that also cause other stuff" wouldn't be a very good headline...

N. M. Williams et al (2010). Rare chromosomal deletions and duplications in attention deficit hyperactivity disorder: a genome-wide analysis The Lancet

Freudian psychoanalysis is the key to treating depression, especially the post-natal kind (depression after childbirth). That's according to a Guardian article by popular British psychologist and author Oliver James. He says that recent research has proven Freud right about the mind, and that psychoanalysis works better than other treatments, like cognitive-behavioural therapy (CBT).

Neuroskeptic readers have encountered James before. He's the person who thinks that Britain is the most mentally-ill country in Europe. I disagree, but that's at least a debatable point. This time around, James's claims are just plain wrong.

So, some corrections. We've got a lot to cover, so I'll keep it brief:

"10% [of new mothers] develop a full-blown depression...which therapy should you opt for? [antidepressants] rule out breastfeeding" - No, they don't. Breast-feeding mothers are able to use antidepressants when necessary, according to the British medical guidelines and others:

Limited data on effects of SSRI exposure via breast milk on weight gain and infant development are encouraging. If a woman has been successfully treated with a SSRI in pregnancy and needs to continue therapy after delivery, there is no need to change the drug, provided the infant is full term, healthy and can be adequately monitored...

James's statement is a dangerous mistake, which could lead to new mothers worrying unduly, or even stopping their medication.

"People given chalk pills but told they are antidepressants are almost as likely to claim to feel better as people given the real thing." - This is true in many cases, although it's a little bit more complicated than that, but this refers to trials on general adult clinical depression, not post-natal depression, which might be completely different.

There's actually only one trial comparing an antidepressant to chalk placebo pills in post-natal depression. The antidepressant, Prozac, worked remarkably well, much better than in most general adult trials. This was a small study, and we really need more research, but it's encouraging.

"Regarding the talking therapies, in one study depressed new mothers were randomly assigned to eight sessions of CBT, counselling, or to psychodynamic psychotherapy. Eighteen weeks later, the ones given dynamic therapy were most likely to have recovered (71%, versus 57% for CBT, 54% counselling)."

This is cherry-picking. In the trial in question the dynamic (psychoanalytic) therapy was slightly better than the other two when depression was assessed in one way, which is what James quotes. The difference was not statistically significant. And using another depression measurement scale, it was no better at all. Take a look, it's hardly impressive:

Plus, after 18 weeks, none of the three psychotherapies was any better to the control, which consisted of doing precisely nothing at all.

"Studies done in the last 15 years have largely confirmed Freud's basic theories. Dreams have been proven to contain meaning." - Nope. Freud believed that dreams exist to fulfil our fantasies, often although not always sexual ones. We dream about what we'd like to do. Except we don't actually dream about it, because we'd find much of it shameful, so our minds hide the true meaning behind layers of metaphor and so forth. "Steep inclines, ladders and stairs, and going up or down them, are symbolic representations of the sexual act..."

If you believe that, good for you, and some people still do, but there has been no research over the past 15 years supporting this (although this is quite interesting). There was never any research really, just anecdotes

"Early childhood experience has been shown to be a major determinant of adult character." Nope. The big story over the past decade is that contra Freud, "shared environment", i.e. family life and child rearing make almost no contribution to adult personality, which is determined by a combination of genes and "individual environment" unrelated to family background. One could argue about the merits of this research but to say that modern psychology is moving towards a Freudian view is absurd. The opposite is true.

"And it is now accepted by almost all psychologists that we do have an unconscious and that it can contain material that has been repressed because it is unacceptable to the conscious mind." Nope. Some psychologists do still believe in "repressed memory" theory, but it's highly controversial. Many consider it a dangerous myth associated with "recovered memory therapy" which has led to false accusations of sexual abuse, Satanic rituals, etc. Again, they may be wrong, but to assert that "almost all" psychologists accept it is bizarre.

"Although slow to be tested, the clinical technique [of Freudian psychoanalysis] has now also been demonstrated to work. The strongest evidence for its superiority over cognitive, short-term treatments was published last year..."

First off, the trial referred to was not about post-natal depression, and it didn't test cognitive therapy at all. It compared long-term psychodynamic therapy, vs. short-term psychodynamic therapy, vs. "solution-focused therapy" in the treatment of various chronic emotional problems. No CBT was harmed in the making of this study.

After 1 year, long-term dynamic therapy was the worst of the three. At 2 years, they were the same. At 3 years, long-term dynamic therapy was the best. Although all these differences were small. Short-term dynamic therapy was no better than solution-focused therapy, which is rather a point against psychoanalysis since solution-focused therapy is firmly non-Freudian. And amusingly, the "short-term" dynamic therapy was actually twice as long as the dynamic therapy in the first study discussed above, which James praised! (20 weekly sessions vs 10). (Edit 23.10.09)


James ends by slagging off CBT and its practitioners, and suggesting that we need a "Campaign for Real Therapy", i.e. not CBT, something he has suggested before. This is the key to understanding why James wrote his muddled piece.

The British government is currently pouring hundreds of millions into the IAPT campaign which aims to "implement National Institute for Health and Clinical Excellence (NICE) guidelines for people suffering from depression and anxiety disorders". NICE guidelines essentially only recommend CBT, so this is effectively a campaign to massively expand CBT services. CBT is widely seen as the only psychotherapy which has been proven to work, in Britain and increasingly elsewhere too.

Oliver James, like quite a lot of people, doesn't like this. And in that, he has a point. There are serious debates to be had over whether CBT is really better than other therapies, and whether we really need lots more of it. There are also serious debates to be had over whether antidepressants are really effective and whether they are over-used. But these are all extremely complex questions. There are no easy answers, no short cuts, no panaceas, and James's brand of sectarian polemic is exactly what we don't need.

[BPSDB]

Or so says Oliver James(*) on this BBC radio show in which he also says things like "I absolutely embraces the credit crunch with both arms".

Oliver James is a British psychologist best known for his theory of "Affluenza". This is his term for unhappiness and mental illness caused, he thinks, by an obsession with money, status and possessions. Affluenza, James thinks, is especially prevanlent in English-speaking countries, because we're more into free-market capitalism than the people of mainland Europe. In fact, he regularly makes the claim that we in Britain, the U.S., Australia etc. are today twice as likely to be mentally ill as "the Europeans". This is because rates of mental illness supposedly surged in the English-speaking world due to 1980s Reagan/Thatcher free market policies. Hence why he welcomes the current economic unpleasantness.

Were all of this true, it would be incredibly important. Certainly important enough to justify writing three books about it and seemingly endless articles for the Guardian. But is it true? Well, this is Neuroskeptic, so you can probably guess. Also, bear in mind that James is someone who is on record as thinking that

[The Tears for Fears song] Mad World. With the chilling line "The dreams in which I'm dying are the best I've ever had", in some respects it is up there with TS Eliot's Prufrock as a poetic account of bourgeois despair.

Obviously poetic taste is entirely subjective etc., but honestly.

Anyway, where did James get the twice-as-bad-as-Europe (or, in some articles, three times as bad) idea from? He says the World Health Organization. Presumably he is referring to one of the World Health Organization's World Mental Health Surveys, such as the analysus presented in this JAMA paper.

At first glance, you can see what he means. This paper reports that the % of people reporting suffering from at least one mental illness over the last year was far higher in the US (26.4%) than in say Italy (8.2%), or Nigeria (4.7%). But on closer inspection, even this data includes some incongruous numbers. Why is Beijing (9.1%) twice as bad as Shanghai (4.3%)? Worse, why does France have a rate of 18.4% while across the border in Germany it's just 9.1%? Are the French twice as materialistic as the Germans? The answer, of course, is that these numbers are more complicated than they appear. In fact, if you believe those figures at face value, you are...well, you're probably Oliver James.

These numbers come from structured interviews, conducted by trained lay researchers, of a random sample of the population. In other words, some guy asked some random people a series of fairly personal questions, reading them off a list, and if they said "Yes" to questions like "Have you ever in your life had a period lasting several days or longer when most of the day you felt sad, empty or depressed?" they might get a tick for "depression". We know this because the interviews used the WHO-CIDI screening questionaire, the first part of which is here.

As part of my own research, I have been that guy asking the questions (in a slightly different context). At some point I'll write about this in more detail, but suffice to say that it's hard to trying to retrospectively diagnose mental illness in someone you've never met before. The potential for denial, mis-remembering, malingering, forgetting or just plain failure to understand the questions is enormous, although it doesn't come across in the final data, which looks lovely and neat.

The authors of the JAMA paper are well aware of this which is why they're skeptical of the apparantly large cross-national differences. In fact, most of their comment section consists of caveats to that effect. Just a few (edited, emphasis mine - see the full paper for more, it's free):

An important limitation of the WMH surveys is their wide variation in response rate. In addition, some of the surveys had response rates below normally accepted standards [i.e. many people refused to participate]... performance of the WMH-CIDI could be worse in other parts of the world either because the concepts and phrases used to describe mental syndromes are less consonant with cultural concepts than in developed Western countries [almost certainly they are] or because absence of a tradition of free speech and anonymous public opinion surveying causes greater reluctance to admit emotional or substance-abuse problems than in developed Western countries. [again, almost certainly, and Europeans are generally more reserved than Americans in this regard.] ... some patterns in the data (e.g. the much lower estimated rate of alcoholism in Ukraine than expected from administrative data documenting an important role of alcoholism in mortality in that country) raise concerns about differential validity.

There's another, more fundamental problem with this data. On any meaningful criterion of "mental illness", a society in which 25% people were mentally ill in any given year would probably collapse. The WHO survey, however, is based on the DSM-IV criteria of mental illness. These are are increasingly regarded as very broad; for example, DSM-IV does not distinguish between feeling miserable & down for two weeks because your boyfriend leaves you, and spending a month in bed hardly eating for no apparant reason. Both are classed as "depression", and hence a "mental illness", although 50 years ago, only the second would have been considered a disease. For someone who styles himself a rebel in the mould of R. D. Laing, it's baffling that James accepts the American Psychiatric Association's dubious criteria.

What other data could we look at? Ideally, we want a measure of mental illness which is meaningful, objective and unambigious. Well, there aren't any, but suicide rates might be the next best thing - they're nice hard numbers which are difficult to fudge (although in cultures in which suicide is strongly taboo, suicides may be reported as deaths from other causes.) Although not everyone who commits suicide is mentally ill, it is fair to say that if Britain really were twice as unhappy as the rest of Europe, we would have a relatively high suicide rate.

What's the data? Well, according to Chishti et. al. (2003) Suicide Mortality in the European Union, we don't.
In fact suicide rates in the UK are boringly middle of the road. They're higher than in places like Greece and Spain, but well below rates in France, Sweden and Germany. Suicide rates are not a direct measure of rates of mental illness, because not everyone who commits suicide is mentally ill, and the rate of succesful suicide depends upon access to lethal means. But does this data look compatible with James's claim that rates of "mental illness" are twice as high in Britain as on "the Continent"? - or indeed with James's implicit assumption that "the Continent" is monolithic?

What's odd is that James clearly knows a bit about suicide, or at least he does now, because just today he wrote a remarkably sensible article about suicide statistics for the Guardian. So he really ought to know better.

Drug sales are another nice, hard number. Of course, medication rates do not equal illness rates - in any field of medicine, but especially psychiatry. Doctors in some countries may be more willing to use drugs, or patients may be more willing to take them. With that in mind, the fact that population-adjusted (source, also here) British sales of antidepressants drugs are twice those of Ireland and Italy, equal to those of Spain, and half those of France, Norway and Sweden does not necessarily mean very much. But it hardly supports James's theory either.

Interestingly, although James holds up Denmark as an example of the kind of happy, "unselfish capitalism" that we should aspire to, the Danes take 50% more antidepressants than we do! (They also have a much higher suicide rate.) True, sales of anxiety drugs and sleeping pills are relatively high in the UK, but still less than Denmark's. Most interestingly, sales of antipsychotics are very low in the UK - roughly the same as in Germany and Italy but less than a quarter of the sales in Ireland and Finland!

So cheer up, Anglos. We're not twice as sad as the French. More likely, we are just more open about talking our problems in the interests of scientific research. However, the French, to their credit, didn't give the world Oliver James.

[BPSDB]

(*) This is Oliver James, psychologist. Not to be confused with: Oliver James, heartthrob actor; Oliver James, Fleet Foxes song, and Oliver James, Ltd.

The WHO World Mental Health Survey Consortium (2004). Prevalence, Severity, and Unmet Need for Treatment of Mental Disorders in the World Health Organization World Mental Health Surveys JAMA: The Journal of the American Medical Association, 291 (21), 2581-2590 DOI: 10.1001/jama.291.21.2581