DSM-5: A Ruse By Any Other Name...

In psychiatry, "a rose is a rose is a rose" as Gertrude Stein put it. That's according to an editorial in the American Journal of Psychiatry called: The Initial Field Trials of DSM-5: New Blooms and Old Thorns.

Like the authors, I was searching for some petal-based puns to start this piece off, but then I found this "flower with an uncanny resemblance to a MONKEY" which I think does the job quite nicely:

Anyway, the editorial is about the upcoming, controversial fifth revision to the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association (APA).

A great deal has been written about the DSM-5 over the past few years, as "the rough beast, its hour come round at last / Slouches towards Bethlehem to be born" (see, I can reference early-20th-century poetry too).

But now the talk has moved into a new phase, because the results of the DSM-5 'field trials' are finally out. In these studies, the reliability of the new diagnostic criteria for different psychiatric disorders was measured. The new editorial is a summary and discussion of the field trial data.

Two different psychiatrists assessed each patient, and the agreement between their diagnoses was calculated, as the kappa statistic, where 0 indicates no correlation at all and 1 is perfect.

It turns out that the reliabilities of most DSM-5 disorders were not very good. The majority were around 0.5, which is at best mediocre. These included such pillars of psychiatric diagnosis like schizophrenia, bipolar disorder, and alcoholism.

Others were worse. Depression, had a frankly crap kappa of 0.28, and the new 'Mixed Anxiety-Depressive Disorder' came in at -0.004 (sic). It was completely meaningless.

The American Journal editorial was written by a group of senior DSM-5 team members. I'm sure they wanted to write a triumphant presentation of their work, but in fact the tone is subdued, even apologetic in places:

As for most new endeavours, the end results are mixed, with both positive and disappointing findings...Experienced clinicians have severe reservations about the proposed research diagnostic scheme for personality disorder...like its predecessors, DSM-5 does not accomplish all that it intended, but it marks continued progress for many patients for whom the benefits of diagnoses and treatment were previously unrealized.

Remember: this is the journal published by the organization responsible for the DSM and even they don't much like it.

But the real story is even worse. The previous editions of the DSM also conducted field trials. These trials had a system to describe different kappa values: for example, 0.6-0.8 was 'satisfactory'.

However, the new DSM-5 studies used a different, lower threshold. They simply moved the goalposts, deeming lower kappa values to be good. At one point, they wrote that values of above 0.8 would be 'miraculous' and above 0.6 a 'cause for celebration', yet this wasn't the view of previous DSM developers.

The indispensable 1boringoldman blog has a nice graphic showing the results of the DSM-5 trials, with the kappas graded according to the old vs. the new criteria. As you can see, the grass is greener on the new side.

The fact is that the DSM-5 field trial results are worse than the results from DSM-III, the 1980 version that's served mostly unchanged for 30 years (DSM-IV made fairly modest changes.) The reliabilities have got worse - despite the editorial's claims of 'continued progress'. It's true that the DSM-5 field trials were a lot bigger and conducted rather differently, but still, it's a serious warning sign.

Finally, there was great variability in the results between different hospitals - in other words the reliability scores were not, themselves, reliable. Some institutions achieved much higher kappa values than others, but it's anyone's guess how they managed to do so.

Still, there's great news: the DSM-5 is just a piece of paper (well, a big stack of them). Any psychiatrist is free to ignore it - as the creator of the more reliable DSM-IV (not III, oops) is now urging them to do.

Freedman R, Lewis DA, Michels R, Pine DS, Schultz SK, Tamminga CA, Gabbard GO, Gau SS, Javitt DC, Oquendo MA, Shrout PE, Vieta E, and Yager J (2013). The Initial Field Trials of DSM-5: New Blooms and Old Thorns. The American Journal of Psychiatry, 170 (1), 1-5 PMID: 23288382

The New "Mood Disorder" That Isn't One

The storied history of "Disruptive Mood Dysregulation Disorder (DMDD)", a controversial new child psychiatric disorder proposed for inclusion in the new DSM-5 manual, continues.

If DSM-5 is officially published (it's due in 2013), kids will be deemed DMDD if they show

severe recurrent temper outbursts that are grossly out of proportion in intensity or duration to the situation.

At least three times a week. Would giving that label be helpful?

Pittsburg psychiatrists David Axelson and colleagues have just shown that the DMDD concept is deeply flawed. They took a large sample of kids assessed for emotional or behavior problems, and compared those who would meet the new DMDD criteria, to those who wouldn't.

"DMDD" turned out not to be correlated with anxiety or mood symptoms in either the child or their parents - rather unusual for a so-called 'Mood Dysregulation Disorder' which is found in the 'Depressive Disorder' section of the DSM-5.

However, DMDD was correlated with - and in fact "could not be delimited from" - two existing disorders, "Conduct Disorder" and "Oppositional Defiant Disorder". It wasn't even a more severe form of those disorders, it was pretty much the same thing.

So, DMDD seems to be nothing to do with mood, but instead covers a pattern of misbehavior which is already covered by not one but two labels already. Why add a misleadingly-named third?

Well, the back-story is that in the past ten years, many American kids and even toddlers have got  diagnosed with 'child bipolar disorder'  - a disease considered extremely rare everywhere else. To stop this, the DSM-5 committee want to introduce DMDD as a replacement. This is the officially stated reason for introducing it. On the evidence of this paper and others it wouldn't even achieve this dubious goal.

The possibility of just going to back to the days when psychiatrists didn't diagnose prepubescent children with bipolar (except in very rare cases) seems to not be on the table.

Axelson D, et al (2012). Examining the proposed disruptive mood dysregulation disorder diagnosis in children in the Longitudinal Assessment of Manic Symptoms study. The Journal of Clinical Psychiatry, 73 (10), 1342-50 PMID: 23140653

Psychiatrists: Does Fire Put Out Fire?

If you're trying to fight fire, should you use fire?

This, pretty much, is the question asked by a group of psychiatrists in a new paper: Will disruptive mood dysregulation disorder (DMDD) reduce false diagnosis of bipolar disorder in children?

The background here is that there's growing concern that bipolar disorder, previously thought to be extremely rare in prepubescent children, is now being diagnosed, inappropriately, in children - specifically in American children. This epidemic of so-called "pediatric bipolar disorder" (PBD) shows no signs of abating.

In response to these concerns, the proposed new fifth edition of the Diagnostic and Statistical Manual (DSM-5) is slated to introduce a new disorder - DMDD. The stated purpose of DMDD is to prevent children getting a diagnosis of PBD - but only by giving them another diagnosis instead.

As I said in 2010 (note, TDDD is the old name of DMDD)

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? ... Can't we just decide to diagnose people less? Apparently, that would be a rather too radical change...

Now, according to the authors of the new paper, if DMDD becomes an official diagnosis, it would only slightly reduce the number of PBD diagnoses - and

If indeed DMDD is a true entity, we suspect that, like bipolar disorder, it, too, will be overdiagnosed.

This was based on a study of 82 kids who were admitted to a specialist children's psychiatric hospital. Of the children, 30% met DMDD criteria based on parental report - but only half of those diagnoses were confirmed by observation of the child'd behaviour in hospital. Parents, in other words, over-rated DMDD symptoms. A rigorous DMDD diagnosis would only "save" a minority of children from a PBD diagnosis.

Even in those cases where "DMDD" seems most justified, it's really not clear who would benefit from giving them another diagnosis because they always qualified for 3 or more other diagnoses. Take a look at this table, showing the frankly ridiculous array of "different" disorders diagnosed in 12 children - the ones who were rated most likely to be "bipolar" by parental report -

Many parents reported "bipolar" symptoms but only 2 of 12 were judged to be actually bipolar; those two incidentally were aged 11 and 12 - consistent with the old view that bipolar is very rare before puberty.

So even if DMDD is a marginally better diagnosis than PBD - do we really need to give out any more diagnoses to kids like this?

The funny thing is that overdiagnosis of PBD is just about the only concern that the DSM-V committee is responding to at all. There are plenty of other well-publicized concerns: overdiagnosis of ADHD, overdiagnosis of depression... most of these are about overdiagnosis to be honest. Anyway, in those cases, DSM-V is proposing to either do nothing much, or actually expand the diagnostic criteria.

For PBD, they are at least trying, so perhaps they deserve some points for effort.

Margulies DM, Weintraub S, Basile J, Grover PJ, and Carlson GA (2012). Will disruptive mood dysregulation disorder reduce false diagnosis of bipolar disorder in children? Bipolar disorders, 14 (5), 488-96 PMID: 22713098

DSM-5 R.I.P?

Yesterday, the proposed new DSM-5 revision of the American Psychiatric Associations "Bible of Psychiatry" came under yet more criticism.

Aaron T. Beck, the father of currently-mega-popular cognitive behavioural therapy, started it off with an attack on the upcoming changes to one diagnosis, Generalized Anxiety Disorder; but many of the points also apply to the other DSM-5 proposals:

The lack of specific features, which is the primary issue for GAD, will not be addressed in DSM-5. The hallmark of the condition will remain pathological worry, although it also characterizes other disorders. Likewise, the proposed behavioral diagnostic criteria lack specificity for GAD, and it is not clear how these will be assessed. The proposed changes will lower the diagnostic threshold for GAD in DSM-5... many currently subthreshold cases will qualify for this diagnosis. The likely inclusion of many such "false-positives" will result in an artificial increase in the prevalence of GAD and will have further negative consequences.

Then from across the Atlantic, and also across the psychotherapy-vs-medication divide, came another piece of criticism. The authors are all associated with the European Medicines Agency (EMA, Europe's equivalent of the FDA), or with national drug regulators. Although they're writing in a personal capacity, this is still big news if you ask me.

These authors start out by saying that the EMA is broadly in favour of DSM reform, but they then attack one of the key DSM-5 innovations - the move towards 'dimensional measures' of symptoms in addition to diagnoses:

One of our main concerns is related to potential future [drug] indications based on an effect on a dimension that is independent of diagnostic categories (although we acknowledge that non-specific claims are common in other areas, such as analgesics for pain). As an example, cognitive impairments are common in psychiatric disorders, but they do not have a unique clinical pattern or a unitary cause.

We therefore believe that, at present, such a cross-cutting approach may increase heterogeneity in patient populations and make the assessment of the benefit–risk balance more difficult. Similarly, the use of dimensions as key secondary end points in many different diagnostic categories may lead to pseudospecific indications and polypharmacy. As a general rule, a therapeutic indication should be a well-recognized clinical entity that is clearly distinguishable from other conditions...

They also echo Beck in warning of over-diagnosis and over-medicalization:

Current proposals to reclassify some conditions that were subthreshold or prodromal as distinct syndromes or disorders could have implications for clinical trials. The inclusion of milder or very early cases of psychiatric disorders may lead to an increase in the number of non-disordered (false-positive) patients in clinical trials, and to an increase in the placebo effect, as less severe cases are more likely to respond to placebo. It may therefore be difficult to show a statistically significant difference [of drug over placebo]...

This raises another highly controversial issue: the risk of medicalization of the normal population. In this respect, a strong concern comes from the proposal to remove bereavement exclusion from the criteria for major depressive disorder, implying that all individuals with ‘normal grief’ might be considered as patients in the future.

Regular readers will remember that I've covered both overdiagnosis screwing up clinical trials, and the bereavement debate.

Two and a half years ago, shortly after the first draft of the DSM-5 was made public, I predicted that the eventual release of DSM-5 would be a non-event because, by then, it would have been widely debated and criticized, destroying the illusion of expert consensus that any such document must have in order to succeed.

I think events have borne this out. An awful lot of professionals, patients, and their relatives, will reject the changes in favour of sticking with the DSM-IV or other criteria. Without swift and general acceptance, a document like the DSM is just paper. It seems increasingly likely that the DSM-5 is going to be dead on arrival.

Starcevic V, Portman ME, & Beck AT (2012). Generalized anxiety disorder: between neglect and an epidemic. The Journal of nervous and mental disease, 200 (8), 664-7 PMID: 22850300

Florence Butlen-Ducuing et al (2012). DSM‑5 and clinical trials in psychiatry: challenges to come? Nature Reviews: Drug Discovery DOI: 10.1038/nrd3811

Shyness By Any Other Name

People think of "social anxiety disorder" as more serious than "social phobia" - even when they refer to exactly the same thing.

Laura C . Bruce et al did a telephone survey of 806 residents of New York State. They gave people a brief description of someone who's uncomfortable in social situations and often avoids them. The question was: should they seek mental health treatment for this problem?

When the symptoms were labelled as "social anxiety disorder", 83% of people recommended treatment. But when the same description was deemed "social phobia", it dropped to 75%, a statistically significant difference.

OK, that's only an 8% gap. It's a small effect, but then the terminological difference was a small one. "Anxiety disorder" vs "Phobia" is about a subtle a distinction as I can think of actually. Imagine if one of the options had been a label that didn't imply anything pathological - "social anxiety" or "shyness". That would probably have had a much bigger impact.

This matters, especially in regards to current debates over the upcoming DSM-5 psychiatric diagnostic manual. Lots of terminological changes are planned. This study is a reminder that even small changes in wording can have an impact on how people think about mental illness. Last week I covered another recent piece of research showing that beliefs about other people's emotions affect how people rate their own mental health.

My point is: DSM-5 will not merely change how professionals talk about the mind. It will change how everyone thinks and behaves.

Bruce, L. (2012). Social Phobia and Social Anxiety Disorder: Effect of Disorder Name on Recommendation for Treatment American Journal of Psychiatry, 169 (5) DOI: 10.1176/appi.ajp.2012.11121808

Are Psychologists All Mad?

A fun little study from 2008 looked at rates of self-reported mental illness in mental health professionals: Psychologists' And Social Workers' Self-Descriptions Using DSM-IV Psychopathology

The authors did an anonymous survey of clinical psychologists and social workers in Israel.  They found that

The sample of 128 professionals included 63 psychologists and 65 social workers. The presence of Axis I traits (i.e. mental illness) was reported by 81.2%, the three most frequent traits being mood, obsessive-compulsive disorder, and eating disorder. Axis II traits (personality disorders) were reported by 73.4% of subjects, the three most frequent conditions being narcissistic, avoidant, and obsessive-compulsive personality traits.

Take a look:

There were few differences between the two professions although for what it's worth, social workers were more likely to report psychosis and substance abuse problems, while clinical psychologists were more narcisstic, with a full 40% of them admitting to having narcisstic traits. On that note the authors (perhaps unwisely) comment:

While speculative, it may be suggested that narcissistic traits include some important factors in motivating individuals to choose to enter the mental health care profession. In a psychotherapeutic relationship, the  ability to influence and understand another person's psyche may include features of  "narcissistic gratification".

Ouch!

The problem with all this, though, is that it's not clear what reporting "DSM-IV psychopathology" means; people rated their symptoms on a 5 point scale where 1 = "no evidence of the disorder" and 5 is "greatest severity". Most of the reported symptoms were low in severity, but we don't know what "low" is relative to.

If you said that your narcissism was rated "2" out of 5, you might just mean that you have some narcissistic traits sometimes. That's how I'd interpret the question, anyway.

But in that case, what exactly are you saying? Not much. You're not saying you're very narcissistic. You're not saying you're more narcissistic than average: you might well think that most other people would also score a "2", or even higher. You're not actually saying "I am narcissistic" at all, just admitting that you're not wholly un-narcissistic... and who of us can really say that?

The same goes for all the questions. I think this study would have been much more interesting if they'd just asked people whether, in their clinical judgement, they meet criteria for the disorder. Or whether, if they had to assess a patient who was just like them, what would they diagnose them with? Because criteria are what professionals use on their patients, not 5 point scales.

Nachshoni, T., Abramovitch, Y., Lerner, V., Assael-Amir, M., Kotler, M., and Strous, R. (2008). Psychologists' And Social Workers' Self-Descriptions Using DSM-IV Psychopathology Psychological Reports, 103 (1), 173-188 DOI: 10.2466/pr0.103.1.173-188

Preventing Psychosis?

Can we prevent psychosis?

In a major study just published, Early detection and intervention evaluation for people at risk of psychosis, 288 young British adults who were deemed to be 'at risk of psychosis' were randomized to get cognitive therapy (CT) or a control condition. The hope was that it could prevent transition to serious psychotic illness.

The primary outcome measure was how many of them later went on to get diagnosed with full-blown psychosis. 2 years later, 7% of the CT group and 9% of the controls had, so that's no significant benefit of treatment. CT slightly reduced the level of mild psychotic-like symptoms, but not how much distress they caused.

So, in other words, no we can't prevent psychosis, not with CT alone at any rate. But there's lots more interesting stuff here...

Now a transition rate of some 8% over 2 years is lower than in previous studies and might suggest that the concept of the 'psychosis risk syndrome'  or 'at-risk mental state' (under consideration for inclusion in DSM-5) is a bit dodgy. The venerable Prof. Allen Frances thinks so. But he misses the fact that the rate was 18% when you also count the people who went psychotic during the baseline assessments (to be fair to Frances, the authors buried that bombshell quite deep in the Discussion).

Still, that's still 82% false positives. Is that too high?

We can't tell, from a study like this. As in any disease screening program, we need to know the relative costs and benefits of true and false 'hits', as well as the percentages of them.

Here's some food for thought on that note. One of the key tenets of the CT model of psychosis is that 'psychotic' symptoms are a more or less normal response to stress, and that psychosis is maintained by a cycle of thoughts and feelings in which these experiences are themselves a source of concern, because they're felt to be abnormal, pathological, or otherwise threatening, thus leading to more stress, and more symptoms, and hence more concern... and so on. CT aims to break that cycle.

Check it out (image from here, coauthored by Graham Dunn, senior author of the present work.)

If you accept that, then it seems that literally the worst possible thing you could say to someone in the 'at risk mental state' is "Watch out! You're at risk of going psychotic!" According to CT, exactly that line of thinking is the root of the whole problem.

The authors of this paper indeed write that "Key ingredients of the approach [include] a focus on normalising psychotic-like experience". But who deemed them abnormal in the first place? The patient, all by themselves... or some well-meaning professional? It's not clear.

We are told that the patients were "seeking help for symptoms", but why? Of their own accord, or after someone else raised concerns? 45 people were referred to the study but excluded because they said that they didn't want help. So there was at least some degree of professional 'railroading', driven by the idea that people with such symptoms ought to seek help

If you accept the CT account of psychosis, then I'd say you ought to think very seriously about whether this whole thing isn't equivalent to giving everyone an X-ray to detect cancers. The X-rays might end up causing more tumours than they find.

I wonder if the authors of this study considered this.

Anyway. Keith Laws of LawsNeuroBlog has a good post about the study and the rather overexcited way it's been received in the press (even, er, the BMJ...)

Despite the authors not being able to make any claims about CT positively affecting transition rates... and the lack of any medication analysis (in fact all patients were unmedicated as an entry requirement) they conclude:

"On the basis of low transition rates, high responsiveness to simple interventions such as monitoring, a specific effect of cognitive therapy on the severity of psychotic symptoms, and the toxicity associated with antipsychotic drugs, we would suggest that antipsychotics are not delivered as a first line treatment to people meeting the criteria for being in an at risk mental state"

So the article in the UK Guardian entitled Drugs not best option for people at risk of psychosis, study warns is not simply misunderstanding by a journalist, but what looks like author spinning.... The BMJ press release itself is headlined Cognitive therapy helps reduce severity of distress among psychotic patients - even though the paper (and the press release itself!) clearly states:

"Cognitive therapy did not significantly affect distress related to these psychotic experiences...nor levels of depression, social anxiety, or satisfaction with life..."

Morrison, A., French, P., Stewart, S., Birchwood, M., Fowler, D., Gumley, A., Jones, P., Bentall, R., Lewis, S., Murray, G., Patterson, P., Brunet, K., Conroy, J., Parker, S., Reilly, T., Byrne, R., Davies, L., and Dunn, G. (2012). Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial BMJ, 344 (apr05 1) DOI: 10.1136/bmj.e2233

DSM-5: A Little Mix Up

Proposals in the upcoming DSM-5 psychiatric manual for diagnosing "mixed" mood states may be muddled, according to a new paper.

The mixed state - the name alluding to a mix between depression and mania - has traditionally been viewed (more or less) as combining the dysphoria of depression with the energy of mania. Anger, agitation, restlessness and so forth.

I've been depressed and I know only too well the difference between that "active" depression and the "inactive" kind; if I had to choose, I'd always go for the latter, because at least you're in less danger of doing or saying something you later regret.

However, in the proposals for DSM-5, "mixed" episodes as such will be abolished. Instead, a depressive episode will have "mixed features" if it is associated with at least 3 of 7 symptoms normally seen in (hypo)mania. But - and here's the key novelty - those 7 are only the "good" symptoms of mania. Not things like anger, irritability, insomnia or 'aimless' hyperactivity. (Edit: There are also separate criteria for "mixed" manic and hypomanic episodes).

What will this mean? In a new paper, psychiatrists Perlis, Cusin, and Fava tried to find out. The large STAR*D antidepressant trial recruited people with depression, but it gave everyone the Psychiatric Diagnosis Screening Questionnaire (PDSQ), amongst many other measures. This helpfully included six items on "mania symptoms", which correspond pretty closely to the DSM-V proposed "mixed" features.

Perlis et al found that depressed patients who reported experiencing these "mixed" items had a better response to antidepressant treatment. The more mixed symptoms, the more likely they were to get better on the common SSRI citalopram, even adjusting for other variables.

That's the exact opposite of what you'd expect from a measure of "mixed states", as these are thought to be less responsive to antidepressants - maybe even caused by them. There was no placebo group, so it's unclear why they got better, but either way, it's unexpected; the authors declare themselves "surprised". Hmm. What a mystery...

Or maybe not. These manic symptoms are all things that you're not when you're depressed. The 6 items actually make a good summary of what depression, even agitated depression (except maybe #6) isn't.

So, one interpretation of these results is that people who endorsed these items just weren't depressed, at some point in the 6 months prior to doing the PDSQ. Assuming they were depressed at other points that means their mood was variable over time.

People whose depression is variable might well be more likely to recover than the ones whose depression was unrelenting.

Now Perlis et al do consider this -

further models were fit incorporating the IDS-C30 pleasure and reactivity items; results were essentially unchanged indicating that they are unlikely to be confounded by mood variability per se...

But this assumes that the IDS-C30 questionnaire is a good measure of mood variability in this sample. Maybe it's not, and these data are telling us so. I'd have said that's more likely than the idea that these people were actually both cheerful and depressed at the same time, which seems like a contradiction in terms.

Maybe I'm wrong, and these people did feel that, but the problem is, we can't tell, because no-one actually sat down and asked these people what was going on, or heard their account of what they meant by ticking both the "depressed" and "manic" boxes.

Did they experience a strange mixed emotional state in which they simultaneously depressed and happy? Did their mood see-saw from one day to the next? Or weekly, monthly? Were they depressed in the day and happier in the evening? Were they depressed, then back to normal, leading them to see the normal as a 'high', by comparison with the lows? Were they depressed when sober and happy when drunk? Vice versa? Are they experiencing normal ups and downs and interpreting them as 'mood swings' because they've become convinced, for whatever reason, that they have a mood disorder? Did they just have a poor command of English and weren't really trying to say what the highly-educated investigators assume they were?

Who knows? No-one, because no-one asked. Rely on questionnaire 'measures' (as if emotions can be measured) as a replacement for understanding, and you'll end up where this paper does - with a 'result' that's impossible to understand.

Don't seek, and ye shan't find.

It's not great news for the DSM-5 proposals, either way, although defenders could hold out hope that the differences between those criteria and the PDSQ measure might mean the DSM-5 will perform better...

 Perlis, R., Cusin, C., and Fava, M. (2012). Proposed DSM-5 mixed features are associated with greater likelihood of remission in out-patients with major depressive disorder Psychological Medicine, 1-7 DOI: 10.1017/S0033291712000281

The Network of Mental Illness

A provocative but problematic paper just out offers a new perspective on psychiatric symptoms.

The basic idea is that rather than psychiatric disorders being entities, they are just bundles of symptoms which cause each other:

...symptoms are unlikely to be merely passive psychometric indicators of latent conditions; rather, they indicate properties with autonomous causal relevance. That is, when symptoms arise, they can cause other symptoms on their own. For instance, among the symptoms of MDE we find sleep deprivation and concentration problems, while GAD (generalized anxiety disorder) comprises irritability and fatigue. It is feasible that comorbidity between MDE and GAD arises from causal chains of directly related symptoms; e.g., sleep deprivation (MDE)→fatigue (MDE)→concentration problems (GAD)→irritability (GAD).

The authors seem to have mixed up their labels in the middle there, but you see the drift.

This symptom-based approach stands in contrast to the idea that psychiatric illnesses are underlying things which lead to some symptoms. So it's a challenge to the notion of underlying biological dysfunction (except maybe for specific symptoms) but it's equally incompatible with any theory of underlying psychological causes - there's no room for Freudian unconscious "complexes" here.

So there's something very straightforward and un-mysterious about this model, which will either make it attractive or suspect, depending on whether you think human life is mysterious or not.

What's the evidence? First, the authors do an analysis of the DSM-IV diagnostic manual in terms of symptoms. They take every symptom which is mentioned in at least one diagnosis. They found 439 symptoms in total, over 201 disorders, with many symptoms, such as insomnia, shared between lots of different "disorders".

They then used network analysis to create a kind of graph where the "distance" between the nodes (symptoms) is based on the number of shared diagnoses. They found that while some symptoms are unique to just one disorder, there's a core of highly shared symptoms which form a "giant component"

It's a very clever approach but I wonder what it really tells us. The DSM-IV is not data about mental illness. It's data about what we think about mental illness. Actually, it's not even that: it's data about what a particular set of people, at a particular time, were able to agree upon.

DSM-V is coming soon, and before that we had DSM's I, II and III. What about them? Do they have a different network structure? I'd have thought they would, but we don't know.

We've already seen the kinds of politics that lie behind the decision to include or exclude a diagnosis in the DSM. In the upcoming DSM-V they're seriously proposing to add a new diagnosis ("TDDD"), purely in order to stop people getting another diagnosis (childhood "bipolar").

There is a lot of symptom overlap between TDDD and bipolar disorder. Because one was designed for the purpose of diverting patients from the other. But that doesn't tell us anything about real people with real symptoms. This is an extreme example and to be fair to the authors they do acknowledge some of these problems with the DSM, but still.

The authors then show that the symptomatic closeness between DSM-IV disorders predicts the rates of comorbidity between those disorders, as measured in the American population survey the NCS-R. This is true even of disorders which don't share a common symptom but which are connected indirectly by a mutual friendship, as it were.

Finally they show that a statistical model based on interacting symptoms can predict the prevalence of depression (10% per year according to the NCS-R survey) and GAD (3% per year). It does so much better than a random model in which symptoms randomly interact.

However, I'm not convinced that all these show us that the symptom-network approach is the best model to explain the occurence of these disorders. It only shows us that it's a model that works better than a crazy random model. I'm also not sure that being able to model the NCS-R data is even a good thing, since these data are themselves of questionable validity.

But it's a genuinely interesting approach and well worth following up.

Borsboom D, Cramer AO, Schmittmann VD, Epskamp S, and Waldorp LJ (2011). The small world of psychopathology. PloS one, 6 (11) PMID: 22114671

So Apparantly I'm Bipolar

According to a new paper, yours truly is bipolar.


I've written before of my experience of depression, and the fact that I take antidepressants, but I've never been diagnosed with bipolar.

I've taken a few drugs in my time. On certain dopamine-based drugs I got euphoric, filled with energy, talkative, confident, with no need for sleep, and a boundless desire to do stuff, which is textbook hypomania. So I think I know what it feels like, and I can confidently say that it has never happened to me out of the blue.

On antidepressants, I have had some mild experiences of this type. Ironically, the closest I've come to it was when I quit an SSRI antidepressant. I've also experienced periods of irritability and agitation on antidepressants. Either way, that's antidepressants. Bipolar is when you get high on your own supply of neurotransmitters.

Well, it used to be. Jules Angst et al have got some new, broader criteria for "bipolarity" in depression. They say that manic symptoms in response to antidepressants do count, exactly like out-of-the-blue mania.

What's more, under the new "Bipolar Specifier" criteria, there's no minimum duration. Under existing criteria the symptoms have to last 4 or 7 days, depending on severity. Under the new regime if you've ever been irritable, high, agitated or hyperactive, on antidepressants or not, you meet "Bipolar Specifier" criteria, so long as it was marked enough that someone else noticed it.

All you need is:

an episode of elevated mood, an episode of irritable mood, or an episode of increased activity with at least 3 of the symptoms listed under Criterion B of the DSM-IV-TR associated with at least 1 of the 3 following consequences: (1) unequivocal and observable change in functioning uncharacteristic of the person’s usual behavior, (2) marked impairment in social or occupational functioning observable by others, or (3) requiring hospitalization or outpatient treatment.

The bipolar net just got bigger. And they caught me in it. Me and 47% of depressed people in their study. They recruited 509 psychiatrists from around the world, and got each of them to assess between 10 and 20 consecutive adult depressed patients who were referred to them for evaluation or treatment. A total of 5635 patients were included.

Only 16% met existing DSM-IV criteria for bipolar disorder, so the new system with 47% identified an "extra" 31%, trebling the number of bipolar cases.

A cynic would say that this is a breathtaking piece of psychiatric marketing. You give people antidepressants, then you diagnose them with bipolar on the basis of their reaction to those drugs, thus justifying selling them yet more drugs.

The cynic would not be surprised to learn that this study was sponsored by pharmaceutical company Sanofi.

All investigators recruited received fees, on a per patient basis, from sanofi-aventis in recognition of their participation in the study....The sponsor of this study (sanofi-aventis) was involved in the study design, conduct, monitoring, data analysis, and preparation of the report.

In fairness, the authors do show that patients meeting their criteria tend to have characteristics typical of bipolar people. And they show that their system is at least as good as DSM-IV at picking out these cases:

For example, DSM-IV bipolar patients had a younger age of onset than DSM-IV depressed ones. "Bipolar specifier" patients did too, compared to the 53% who didn't meet the criteria. Same for a family history of manic symptoms, multiple episodes, and shorter episodes. All of those are pretty well established correlates of bipolar disorder.

That's fine, and the results are better than I expected when I picked up this paper. But all this shows us is that the bipolar specifier was no worse than the DSM-IV criteria as applied in this study.

It doesn't tell us whether either was any good.

DSM-IV criteria were used in a mechanical cookbook fashion - symptoms were assessed by the psychiatrist, written down, sent back to the study authors, who then diagnosed them if they ticked enough boxes. Is that a good approach? We don't know.

Most importantly, we have no idea whether these people would do better being treated as bipolar rather than as depressed. The difference being that bipolar people get mood stabilizers. Maybe these people would benefit from mood stabilizers, maybe not. Existing literature on mood stabilizers in bipolar people can't be assumed to generalize to these 47%.

In the discussion, the authors argue that antidepressants are not much good in bipolar people, whereas mood stabilizers are. Fun fact: Sanofi make many of the most popular formulations of valproic acid/valproate , a big selling mood stabilizer.

I think that is no coincidence. Maybe that sounds crazy, but hey, what do you expect? I'm bipolar.

Angst J, Azorin JM, Bowden CL, Perugi G, Vieta E, Gamma A, Young AH, & for the BRIDGE Study Group (2011). Prevalence and Characteristics of Undiagnosed Bipolar Disorders in Patients With a Major Depressive Episode: The BRIDGE Study. Archives of general psychiatry, 68 (8), 791-798 PMID: 21810644

Melancholia In 100 Words

The British Journal of Psychiatry have a regular series called "In 100 Words", which produces some gems. This month they have Melanchola in 100 Words, featuring perhaps the most influential musician you haven't heard of, Robert Johnson.

I got stones in my pathway/And my road seems dark at night/I have pains in my heart/They have taken my appetite.

Robert Johnson, known as the King of the Delta blues singers, distilled into these lines the essence of severe depressive illness – somatic ills, fear and suspicion, emotional and physical pain, nocturnal troubles and struggle against obstacles. The words are one with the powerful, haunting music. ICD-10 and DSM-IV have their place, but poets have often been there before us, and done a better job. We can all learn from Robert Johnson, born just 100 years ago.

I've previously written about the blues and what shade of blue they were talking about, here. But this actually isn't the first Melancholia in 100 Words to appear in the BJP. Here's another one from 2009

Melancholia is a classical episodic depressive disorder that combines mood, psychomotor, cognitive and vegetative components with high suicide risk. In the present psychiatric classification it is buried as a modifier in both bipolar and unipolar depressions. It is hardly used to characterise patients in the clinic or research.

The syndrome is frequently recognised in delusional and agitated depression, and in the elderly. Cortisol or sleep EEG abnormalities are prognostically helpful. Melancholia is particularly responsive to tricyclic antidepressants and electroconvulsive therapy but not to selective serotonin reuptake inhibitors or psychotherapy. Recognising melancholia as a distinct disorder improves clinical care and research.

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

The Neuro Week 12th June

Image of the week is this rather striking picture showing that slime moulds love to digest herbal sleeping tablets. This makes sense, because slime moulds are well known to experience severe insomnia. Because they're moulds, and moulds don't sleep.

Story of the week is that evolutionary biologist and writer Steven J. Gould relied on dodgy statistics in his classic book about race, science and intelligence, The Mismeasure of Man. That's according to a new paper, and there are excellent blog discussions here and here. Gould's to my mind the greatest science writer of all time. But you can write well without always being right.

Many neuroscience and psychology studies could be flawed because the "healthy controls" are just too healthy. This is a serious issue which doesn't get discussed enough.

Did dinosaurs sleep during the day, or the night? Until we get a working time machine, we'll never know for sure, but by examining the shapes of the eyes of different species, a new study has shed light on this question.

Studying psychology at university is not a good idea if you want to get a high salary, according to an upcoming paper.

An interesting legal case from the U.S: judge overturns federal law to impose less than the minimum sentence in a child pornography case. According to Forensic Psychologist blog, the ruling contains discussions of everything from neuroimaging to the arguments over DSM-V.

Psych Your Mind blogger posts his 'favourite' anonymous peer review judgements, along with the suggestion that psychology reviewers seem to be especially vicious compared to those in other fields.

British doctors, charities, and politicians all agreed that antipsychotic drugs are being over-used in dementia this week. Which is something, because they don't agree about anything else right now. I previously blogged about how an earthquake in Italy caused a spike in local elderly people getting these drugs.

The LA Times has an excellent piece on the attempts to build prosthetic limbs with a sense of touch. We've already got artificial retinas, but an artificial sense of touch is even harder, because it requires implanting electrodes directly into the brain.

Mind Hacks discusses a major study into Alzheimer's disease, conducted with the help of a Columbian family with a hereditary form of the disorder.

I can't read everything. So any tipoffs will be gratefully received. Either leave them in a comment or drop me an email.

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

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