DSM-V, a Prenatal Health Check

Last month the proposed draft of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) came out.

In my post at the time I was pretty critical of several aspects of the new DSM. Many many other blogs have discussed DSM-V, as have older media. As you'd expect with such a complex and controversial issue as psychiatric diagnosis, opinions have varied widely, but one thing stands out: people are debating this. Everyone's got something to say about it, professionals and laypeople.

Debate is usually thought to be healthy, but I think in this case, it's a very bad sign for DSM-V. The previous editions, like DSM-IV, were presented to the world as a big list of mental disorders carrying the authority of the American Psychiatric Association. That's why people called the DSM the Bible of psychiatry - it was supposedly revealed truth as handed down by a consensus group of experts. If not infallible, it was at least something to take note of. There have always been critics of the DSM, but until recently, they were the underdogs, chipping away at an imposing edifice.

But DSM-V won't be imposing. People are criticizing it before it's been finalized, and even bystanders can see that there's really no consensus on many important issues. The very fact that everyone's discussing the proposed changes to the Manual is also telling: if the DSM is a Bible, why does it need to be revised so often?

My prediction is that when DSM-V does arrive (May 2013 is the current expected birth date) , it will be a non-event. By then the debates will have happened. I suspect that few researchers are going to end up deciding to invest their time, money and reputation in the new disorders added in DSM-V. Why study "temper regulation disorder with dysphoria" (TDDD) when it was controversial before it even officially existed? Despite the shiny new edition, we may be using DSM-IV for all intents and purposes for a long time to come.

Absinthe Fact and Fiction

Absinthe is a spirit. It's very strong, and very green. But is it something more?

I used to think so, until I came across this paper taking a skeptical look at the history and science of the drink, Padosch et al's Absinthism a fictitious 19th century syndrome with present impact

Absinthe is prepared by crushing and dissolving the herb wormwood in unflavoured neutral alcohol and then distilling the result; other herbs and spices are added later for taste and colour.

It became extremely popular in the late 19th century, especially in France, but it developed a reputation as a dangerous and hallucinogenic drug. Overuse was said to cause insanity, "absinthism", much worse than regular alcoholism. Eventually, absinthe was banned in the USA and most but not all European countries.

Much of the concern over absinthe came from animal experiments. Wormwood oil was found to cause hyperactivity and seizures in cats and rodents, whereas normal alcohol just made them drunk. But, Padosch et al explain, the relevance of these experiments to drinkers is unclear, because they involved high doses of pure wormwood extract, whereas absinthe is much more dilute. The fact that authors at the time used the word absinthe to refer to both the drink and the pure extract added to the confusion.

It's now known that wormwood, or at least some varieties of it, contains thujone, which can indeed cause seizures, and death, due to being a GABA antagonist. Until a few years ago it was thought that old-style absinthe might have contained up to 260 mg of thujone per litre, a substantial dose.

But that was based on the assumption that all of the thujone in the wormwood ended up in the drink prepared from it. Chemical analysis of actual absinthe has repeatedly found that it contains no more than about 6 mg/L thujone. The alcohol in absinthe would kill you long before you drank enough to get any other effects. As the saying goes, "the dose makes the poison", something that is easily forgotten.

As Padosch et al point out, it's possible that there are other undiscovered psychoactive compounds in absinthe, or that long-term exposure to low doses of thujone does cause "absinthism". But there is no evidence for that so far. Rather, they say, absinthism was just chronic alcoholism, and absinthe was no more or less dangerous than any other spirit.

I'm not sure why, but drinks seem to attract more than their fair share of urban myths. Amongst many others I've heard that the flakes of gold in Goldschläger cause cuts which let alcohol into your blood faster; Aftershock crystallizes in your stomach, so if you drink water the morning afterwards, you get drunk again; and that the little worm you get at the bottom of some tequilas apparently contains especially concentrated alcohol, or hallucinogens, or even cocaine maybe.

Slightly more serious is the theory that drinking different kinds of drinks instead of sticking to just one gets you drunk faster, or gives you a worse hangover, or something, especially if you do it in a certain order. Almost everyone I know believes this, although in my drinking experience it's not true, but I'm not sure that it's completely bogus, as I have heard somewhat plausible explanations i.e. drinking spirits alongside beer leads to a concentration of alcohol in your stomach that's optimal for absorption into the bloodstream... maybe.

Link: Not specifically related to this but The Poison Review is an excellent blog I've recently discovered all about poisons, toxins, drugs, and such fun stuff.

Padosch SA, Lachenmeier DW, & Kröner LU (2006). Absinthism: a fictitious 19th century syndrome with present impact. Substance abuse treatment, prevention, and policy, 1 (1) PMID: 16722551

Mmm... Food-Induced Seizures

In a tasty new paper, British neurologists Kate El Bouzidi et al report on the case of a woman who suffered epileptic seizures whenever she saw, smelled, or ate food:

A 44-year-old right-handed woman was walking in the Scottish highlands. Upon unwrapping her lunch, she had a focal seizure with witnessed onset on the right side of the face and secondary generalization... She was airlifted to hospital. Three weeks later, the smell of food triggered another seizure and she was admitted to the neurology unit...

Even hospital fare was able to provoke the attacks:

The next morning, the patient had a simple partial seizure after eating a spoonful of porridge. Thereafter, most meals triggered seizures, as did other food-related stimuli such as being offered a piece of cake, seeing her visitors pass around food at her bedside, and smelling the hospital dinner trolley.

Anti-convulsant drugs failed to control the seizures. An MRI scan revealed an abnormal mass and electrode recordings from the surface of the brain confirmed that the seizure activity was starting nearby. The mass was surgically removed - it turned out to have been a grade IV glioblastoma cancer - which put an end to the seizures, although sadly we're told that the surgery was "subtotal" i.e. they weren't able to remove the tumour entirely.

The authors note that eating-induced seizures have been reported hundreds of times, most commonly in India and Sri Lanka, curiously enough, but this is the first known case in which merely seeing or thinking about food was also a trigger. Why it happens is a mystery: presumably, neural activation in response to the taste or smell of food somehow spills over into the epileptic focus... but the details are sketchy.

In this case, seizures were specifically triggered by food-related stimuli in the context of hunger. The finding of a seizure focus in the left frontal operculum, adjacent to the tumor, is consistent with the hypothesis that activation of this region by appetite triggered seizure activity that then propagated to the surrounding cortex and was manifest clinically as a motor seizure.

El Bouzidi K, Duncan S, Whittle IR, & Butler CR (2010). Lesional reflex epilepsy associated with the thought of food. Neurology, 74 (7), 610-2 PMID: 20157165

How to Stop Smoking

1. Don't smoke.
2. See 1.

This is essentially what Simon Chapman and Ross MacKenzie suggest in a provocative PloS Medicine paper, The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences.

Their point is deceptively simple: there is lots of research looking at drugs and other treatments to help people quit smoking tobacco, but little attention is paid to people who quit without any help, despite the fact that the majority (up to 75%) of quitters do just that. This is good news for the pharmaceutical industry and others who sell smoking-cessation aids, but it's not clear that it's good for public health.

As they put it,

despite the pharmaceutical industry’s efforts to promote pharmacologically mediated cessation and numerous clinical trials demonstrating the efficacy of pharmacotherapy, the most common method used by most people who have successfully topped smoking remains unassisted cessation ... Tobacco use, like other substance use, has become increasingly pathologised as a treatable condition as knowledge about the neurobiology, genetics, and pharmacology of addiction develops. Meanwhile, the massive decline in smoking that occurred before the advent of cessation treatment is often forgotten.

Debates over drugs, or other treatments, tend to revolve around the question of whether they work: is this drug better than placebo for this disorder? Chapman and MacKenzie point out that even to frame an issue in these terms is to concede a lot to the medical or pathological approach, which may not be a good idea. Before asking, do the drugs work? We should ask, what have drugs got to do with this?

Their argument is not that drugs never help people to quit; nor are they saying that tobacco isn't addictive, or that there is no neurobiology of addiction. Rather, they are saying that the biology is only one aspect of the story. The importance of drugs (and other stop-smoking aids like CBT), and the difficulty of quitting, is systematically exaggerated by the medical literature...

Of the 662 papers [about "smoking cessation" published in 2007 or 2008], 511 were studies of cessation interventions. The other 118 were mainly studies of the prevalence of smoking cessation in whole or special populations. Of the intervention papers, 467 (91.4%) reported the effects of assisted cessation and 44 (8.6%) described the impact of unassisted cessation (Figure 1).... Of the papers describing cessation trends, correlates, and predictors in populations, only 13 (11%) contained any data on unassisted cessation.

And although pharmaceutical industry funding of research plays a part in this, the fact that medical science tends to focus on treatments rather than on untreated individuals is unsurprising since this is fundamentally how science works:

Most tobacco control research is undertaken by individuals trained in positivist scientific traditions. Hierarchies of evidence give experimental evidence more importance than observational evidence; meta-analyses of randomized controlled trials are given the most weight. Cessation studies that focus on discrete proximal variables such as specific cessation interventions provide ‘‘harder’’ causal evidence than those that focus on distal, complex, and interactive influences that coalesce across a smoker’s lifetime to end in cessation.

Overall, it's an excellent paper and well worth a read in full (it's short and it's open access). Of course, it is itself only one side of the story and many in the tobacco control community will find it controversial. But I think Chapman and MacKenzie's is a point that needs to be made, and point applies to other areas of medicine, especially, although not exclusively, to mental health. This week, British social care charity Together told us that

Six out of ten of people have had at least one time in their life where they have found it difficult to cope mentally... stress (70%), anxiety (59%) and depression (55%) were the three most common difficulties encountered by the public

Which was not still not quite as good as rivals Turning Point who last month said

Three quarters of people in the UK experience depression occasionally or regularly yet only a third seek help

These were opinion surveys, not real peer-reviewed science, but they might as well have been: the best available science says that if you go and ask people, 50-70% of the population report suffering at least one diagnosable DSM-IV mental disorder in their lifetime, and that the majority receive no treatment at all. This leads to papers in major journals such as this one warning that "Depression Care in the United States" is "Too Little for Too Few."

But we don't know whether these tens of millions of cases of untreated "mental illness" should be treated, because there is basically no research looking at what happens to such people without treatment. On the other hand, the very fact that they aren't treated, and yet manage to hold down jobs, relationships and so forth, suggests that the situation is not so bad.

Of course we must never forget that depression and anxiety can be crippling diseases, but fortunately, such cases are at least comparatively rare. By using the word "depression" to cover everything from waking-up-at-4-am-in-a-suicidal-panic-melancholia to feeling-a-bit-miserable-because-something-bad-just-happened, it's easy to forget that while clinical depression is a serious matter, feeling a bit miserable is normal and resolves without any help 99% of the time. Even though there are no published scientific studies proving this, because it's not the kind of thing scientists study.

Incidentally, this issue is a good reminder that there's no one big bad conspiracy behind everything. With smoking, Big Tobacco find themselves in direct opposition to Big Pharma, like in From Dusk Till Dawn when the psychopaths fight the vampires. With depression, the people who are quickest to decry the widespread use of antidepressants often seem to be the ones who are most keen on the idea that depression is common and under-treated, perhaps because it allows them to recommend their own favorite psychotherapy. Big Pharma hands the baton to Big Couch in the race to medicalize life.

Chapman S, & MacKenzie R (2010). The global research neglect of unassisted smoking cessation: causes and consequences. PLoS medicine, 7 (2) PMID: 20161722

Who Reads Journals?

Yesterday, I was faced with a typically academic dilemma: which journal to submit to?

I'd written a paper, one which, inexplicably, had been rejected by the first journal I tried to publish it in. Actually, like many people I purposefully aimed too high, going for a very good (i.e. high Impact) journal in the first instance, just in case I got lucky. I didn't, so, I started looking for something more realistic, i.e. a bad one.

But this got me thinking. Why does it matter where I send it? So long as it's published in a journal indexed in PubMed, which every even vaguely scientific publication is nowadays, people who'll find it interesting will see it.

Because people don't actually read journals, people search PubMed for papers relating to their field of research, or increasingly, allow an automated service to search it for them. No-one sits down and reads a journal from cover to cover, like a book. Publishing in a good journal looks better on your CV, and it does lend a paper some extra credibility thus perhaps making it more likely to be read, but not by very much. If it's on PubMed, it gets noticed.

Of course, just because I find all my papers through PubMed searches (or blog links, occasionally) doesn't mean everyone else does. But the other academics I know are the same: with the occasional exception of Nature and Science, we don't read journals. I'm sure this is partly a reflection of the fact that most of the academics I know are under 30, so we all grew up using computers and search engines.

However, maybe I'm wrong, but it seems that the same thing increasingly applies to older researchers as well. There are so many journals nowadays that searches are pretty much the only way to keep up to date with relevant papers; it would take too long to read, or even skim, them all.

I'm not sure that this is a good thing, though. It's a cliché that today's scientists are "too specialized" and don't know about anything beyond their own particular research focus. In my experience, it's not quite as bad as many people make out, but the efficiency of PubMed for finding the papers you want means that you're correspondingly less likely to come across papers offering new perspectives that you're not aware of.

Browsing an issue of a journal or even just reading the contents page gets you thinking about work that's not directly related to your own, which is how ideas and collaborations start. If you only read things because you know you're going to be interested in them in advance, you'll stay interested in the same thing for ever...