Normal? You're Weird - Psychiatrists

Almost everyone is pretty screwed up. That's not my opinion, that's official - according to a new paper in the latest British Journal of Psychiatry.

Make sure you're sitting down for this. No less than 48% of the population have "personality difficulties", and on top of that 21% have a full blown "personality disorder", and another 7% have it even worse with "complex" or "severe" personality disorders.

That's quite a lot of people. Indeed it only leaves an elite 22.5% with no personality disturbances whatsoever. You're as likely to have a "simple PD" as you are to have a normal personality, and fully half the population fall into the "difficulties" category.

I have difficulties with this.

Where do these results come from? The Adult Psychiatric Morbidity Survey, which is a government study of the British population. They phoned up a random sample of several thousand people, and gave them the SCID interview, in other words they asked them questions. 116 questions in fact.

48% of people answered "yes" to enough questions such that, according to their criteria, they had "personality difficulties". They defined "personality difficulties", which is not a term in common use, as being "one criterion less than the threshold for personality disorder (PD)" according to DSM-IV criteria.

So what? Well, as far as I'm concerned, that means simply that "personality difficulties" is a crap category, which labels normality as pathological. I can tell that most of people with "difficulties" are in fact normal because they are the literally the norm. It's not rocket science.

So we can conclude that "personality difficulties" should either be scrapped or renamed "normal". In which case the weird minority of people without any such features should be relabelled. Maybe they are best known as "saints", or "Übermenschen", or perhaps "people who lie on questionnaires".

This, however, is not what the authors say. They defend their category of Personality Difficulties on the grounds that this group are slightly more likely to have a history of "issues" than the elite 22.5 percent, e.g. homelessness (3.0% vs. 1.6%), 'financial crisis' (10.1% vs. 6.8%), or having had treatment for mental illness (11% vs 6%).

They say:

The finding that 72% of the population has at least some degree of personality disturbance is counterintuitive, but the evidence that those with ‘personality difficulty’ covering two out of five of the population [it's actually closer to half], differs significantly from those with no personality disturbance in the prevalence of a history of running away from home, police contacts, homelessness... shows that this separation is useful from both clinical and societal viewpoints.

Well, yeah...but no. The vast majority (90+%) of people with Personality Difficulty had no history of these things. It's true that, as a group, they have higher average rates, but all this tells you is that some of them have problems. I suspect they're the ones right at the "top end" of this category, the people who are almost into the next category up.

Here's what I think is going on:

The "difficulties" group and the "none" group are essentially the same in terms of the levels of crap stuff happening to them - because they are the same, normal, everyday people - except that a small % of the "difficulties" group do have some moderate degree of problems, because they are close to being "PD".

This does not mean that the "difficulties" category is good. Quite the reverse, it means it's rubbish, because it spans so many diverse people and lumps them all together. What you should do, if you insist on drawing lines in the sand, would be this:

Now I don't know that that's how things work, but it seems plausible. Bearing in mind that the categories they used are entirely arbitrary, it would be very odd if they did correspond to reality.

To be fair to the authors, this is not the only argument in their paper. Their basic point is that personality disturbance is a spectrum: rather than it being a black-and-white question of "normal" vs."PD", there are degrees, ranging from "simple PD" which is associated with a moderate degree of life crap, up to "complex PD" which has much more and "severe PD" which is worst of all.

They suggest that in the upcoming DSM-V revision of psychiatric diagnosis, it would be useful to formally incorporate the severity spectrum in some way - unlike the current DSM-IV, there everything is either/or. They also argue that with more severe cases of PD, it is not very useful to assign individual PD diagnoses (DSM-IV has no less than 10 different PDs) - severe PD is just severe PD.

That's all fine, as long as it doesn't lead to pathologizing 78% of the population - but this is exactly what it might do. The authors do admit that "the SCID screen for personality disorder, like almost all screening instruments, overdiagnoses personality pathology", but provide little assurance that a "spectrum" approach won't do the same thing.

Yang M, Coid J, & Tyrer P (2010). Personality pathology recorded by severity: national survey. The British Journal of Psychiatry 197, 193-9 PMID: 20807963

Are "Antipsychotics" Antipsychotics?

This is the question asked by Tilman Steinert & Martin Jandl in a letter to the journal Psychopharmacology.

They point out that in the past 20 years, the word "antipsychotic" has exploded in popularity. Less than 100 academic papers were published with that word in the title in 1990, but now it's over 600 per year.

The older term for the same drugs was "neuroleptics". This terminology, however, has slowly but surely fallen into disuse over the same time period.

To illustrate this they have a nice graph of PubMed hits. Neuroskeptic readers will be familiar with these as I have often posted my own and I recently wrote a bash script to harvest this data automatically. Now you too can be a historian of medicine from the comfort of your own home...

Why does it matter what we call them? A name is just a name, right? No, that's the problem. Actually, neuroleptic is just a name, because it doesn't mean anything. The term derives from the Greek "neuron", meaning... neuron, and "lambanō" meaning "to take hold of". However, no-one knows that unless they look it up on Wikipedia because it's just a name.

Antipsychotic, on the other hand, means something: it means they treat psychosis. But whether or not this is an accurate description of what "antipsychotics" actually do, is controversial. For one thing, these drugs are also used to treat many non-psychotic illnesses, like depression, and PTSD.

More fundamentally, it's not universally accepted that they have a direct anti-psychotic effect. All antipsychotics are powerful sedatives. There's a school of thought that says that this is in fact all they are, and rather than treating psychosis, they just sedate people until they stop being obviously psychotic.

Personally, I don't believe that, but that's not really the point: the point is that it's controversial, and calling them antipsychotics makes it hard to think about that controversy in a sensible way. To say that antipsychotics aren't actually antipsychotic is a contradiction in terms. To say they are antipsychotic is a tautology. Names shouldn't dictate the terms of a debate in that way. A name should just be a name.

The same point applies to more than just antipsychotics - I mean neuroleptics - of course. Perhaps the worst example is "antidepressants". Prozac, for example, is called an antidepressant. Implying that it treats depression.

But according to clinical trials, Prozac and other SSRIs are a lot more effective, relative to placebo, in obsessive-compulsive disorders (OCD) than they are in depression (though this is not necessarily true of all "antidepressants", yet more evidence that the word is unhelpful.)

So, as I asked in a previous post: "Are SSRIs actually antiobsessives that happen to be helpful in some cases of depression?" Personally, I think the only name for them which doesn't make any questionable assumptions, is simply 'SSRIs'.

Tilman Steinert and Martin Jandl (2010). Are antipsychotics antipsychotics? Psychopharmacology DOI: 10.1007/s00213-010-1927-3

Marc Hauser's Scapegoat?

The dust is starting to settle after the Hauser-gate scandal which rocked psychology a couple of weeks back.

Harvard Professor Marc Hauser has been investigated by a faculty committee and the verdict was released on the 20th August: Hauser was "found solely responsible... for eight instances of scientific misconduct." He's taking a year's "leave", his future uncertain.

Unfortunately, there has been no official news on what exactly the misconduct was, and how much of Hauser's work is suspect. According to Harvard, only three publications were affected: a 2002 paper in Cognition, which has been retracted; a 2007 paper which has been "corrected" (see below), and another 2007 Science paper, which is still under discussion.

But what happened? Cognition editor Gerry Altmann writes that he was given access to some of the Harvard internal investigation. He concludes that Hauser simply invented some of the crucial data in the retracted 2002 paper.

Essentially, some monkeys were supposed to have been tested on two conditions, X and Y, and their responses were videotaped. The difference in the monkey's behaviour between the two conditions was the scientifically interesting outcome.

In fact, the videos of the experiment showed them being tested only on condition X. There was no video evidence that condition Y was even tested. The "data" from condition Y, and by extension the differences, were, apparently, simply made up.

If this is true, it is, in Altmann's words, "the worst form of academic misconduct." As he says, it's not quite a smoking gun: maybe tapes of Y did exist, but they got lost somehow. However, this seems implausible. If so, Hauser would presumably have told Harvard so in his defence. Yet they found him guilty - and Hauser retracted the paper.

So it seems that either Hauser never tested the monkeys on condition B at all, and just made up the data, or he did test them, saw that they weren't behaving the "right" way, deleted the videos... and just made up the data. Either way it's fraud.

Was this a one-off? The Cognition paper is the only one that's been retracted. But another 2007 paper was "replicated", with Hauser & a colleague recently writing:

In the original [2007] study by Hauser et al., we reported videotaped experiments on action perception with free ranging rhesus macaques living on the island of Cayo Santiago, Puerto Rico. It has been discovered that the video records and field notes collected by the researcher who performed the experiments (D. Glynn) are incomplete for two of the conditions.

Luckily, Hauser said, when he and a colleague went back to Puerto Rico and repeated the experiment, they found "the exact same pattern of results" as originally reported. Phew.

This note, however, was sent to the journal in July, several weeks before the scandal broke - back when Hauser's reputation was intact. Was this an attempt by Hauser to pin the blame on someone else - David Glynn, who worked as a research assistant in Hauser's lab for three years, and has since left academia?

As I wrote in my previous post:

Glynn was not an author on the only paper which has actually been retracted [the Cognition 2002 paper that Altmann refers to]... according to his resume, he didn't arrive in Hauser's lab until 2005.

Glynn cannot possibly have been involved in the retracted 2002 paper. And Harvard's investigation concluded that Hauser was "solely responsible", remember. So we're to believe that Hauser, guilty of misconduct, was himself an innocent victim of some entirely unrelated mischief in 2007 - but that it was all OK in the end, because when Hauser checked the data, it was fine.

Maybe that's what happened. I am not convinced.

Personally, if I were David Glynn, I would want to clear my name. He's left science, but still, a letter to a peer reviewed journal accuses him of having produced "incomplete video records and field notes", which is not a nice thing to say about someone.

Hmm. On August 19th, the Chronicle of Higher Education ran an article about the case, based on a leaked Harvard document. They say that "A copy of the document was provided to The Chronicle by a former research assistant in the lab who has since left psychology."

Hmm. Who could blame them for leaking it? It's worth remembering that it was a research assistant in Hauser's lab who originally blew the whistle on the whole deal, according to the Chronicle.

Apparently, what originally rang alarm bells was that Hauser appeared to be reporting monkey behaviours which had never happened, according to the video evidence. So at least in that case, there were videos, and it was the inconsistency between Hauser's data and the videos that drew attention. This is what makes me suspect that maybe there were videos and field notes in every case, and the "inconvenient" ones were deleted to try to hide the smoking gun. But that's just speculation.

What's clear is that science owes the whistle-blowing research assistant, whoever it is, a huge debt.

Serotonin, Psychedelics and Depression

Note: This post is part of a Nature Blog Focus on hallucinogenic drugs in medicine and mental health, inspired by a recent Nature Reviews Neuroscience paper, The neurobiology of psychedelic drugs: implications for the treatment of mood disorders, by Franz Vollenweider & Michael Kometer. That article will be available, free (once you register), until September 23. For more information on this Blog Focus, see the "Table of Contents" here.

Neurophilosophy is covering the history of psychedelic psychiatry, while Mind Hacks provides a personal look at one particular drug, DMT. The Neurocritic discusses ketamine, an anesthetic with hallucinogenic properties, which is attracting a lot of interest at the moment as a treatment for depression.

Ketamine, however, is not a "classical" psychedelic like the drugs that gave the 60s its unique flavor and left us with psychedelic rock, acid house and colorful artwork. Classical psychedelics are the focus of this post.

The best known are LSD ("acid"), mescaline, found in the peyote and a few other species of cactus, and psilocybin, from "magic" mushrooms of the Psilocybe genus. Yet there are literally hundreds of related compounds. Most of them are described in loving detail in the two heroic epics of psychopharmacology, PIKHaL and TIKHaL, written by chemists and trip veterans Alexander and Ann Shulgin.

The chemistry of psychedelics is closely linked with that of depression and antidepressants. All classical psychedelics are 5HT2A receptor agonists. Most of them have other effects on the brain as well, which contribute to the unique effects of each drug, but 5HT2A agonism is what they all have in common.

5HT2A receptors are excitatory receptors expressed throughout the brain, and are especially dense in the key pyramidal cells of the cerebral cortex. They're normally activated by serotonin (5HT), which is the neurotransmitter that's most often thought of as being implicated in depression. The relationship between 5HT and mood is very complicated, and depression isn't simply a disorder of "low serotonin", but there's strong evidence that it is involved.

There's one messy detail, which is that not quite all 5HT2A agonists are hallucinogenic. Lisuride, a drug used in Parkinson's disease, is closely related to LSD, and is a strong 5HT2A agonist, but it has no psychedelic effects. It's recently been shown that LSD and lisuride have different molecular effects on cortical cells, even though they act on the same receptor - in other words, there's more to 5HT2A than simply turning it "on" and "off".

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How could psychedelics help to treat mental illness? On the face of it, the acute effects of these drugs - hallucinations, altered thought processes and emotions - sound rather like the symptoms of mental illness themselves, and indeed psychedelics have been referred to as "psychotomimetic" - mimicking psychosis.

There are two schools of thought here: psychological and neurobiological.

The psychological approach ruled the first wave of psychedelic psychiatry, in the 50s and 60s. Psychiatry, especially in America, was dominated by Freudian theories of the unconscious. On this view, mental illness was a product of conflicts between unconscious desires and the conscious mind. The symptoms experienced by a particular patient were distressing, of course, but they also provided clues to the nature of their unconscious troubles.

It was tempting to see the action of psychedelics as a weakening of the filters which kept the unconscious, unconscious - allowing repressed material to come into awareness. The only other time this happened, according to Freud, was during dreams. That's why Freud famously called the interpretation of dreams the "royal road to the unconscious".

Psychedelics offered analysts the tantalizing prospect of confronting the unconscious face-to-face, while awake, instead of having to rely on the patient's memory of their previous dreams. To enthusiastic Freudians, this promised to revolutionize therapy, in the same way that the x-ray had done so much for surgery. The "dreamlike" nature of many aspects of the psychedelic experience seemed to confirm this.

Not all psychedelic therapists were orthodox Freudians, however. There were plenty of other theories in circulation, many of them inspired by the theorists' own drug experiences. Stanislav Grof, Timothy Leary and others saw the psychedelic state of consciousness as the key to attaining spiritual, philosophical and even mystical insights, whether one was "ill" or "healthy" - and indeed, they often said that mental "illness" was itself a potential source of spiritual growth.

Like many things, psychiatry has changed since the 60s. Psychotherapy is currently dominated by cognitive-behavioural (CBT) theory, and Freudian ideas have gone distinctly out of fashion. It remains to be seen what CBT would make of LSD, but the basic idea - that carefully controlled use of drugs could help patients to "break through" psychological barriers to treatment - seems likely to remain at the heart of their continued use.

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The other view is that these drugs could have direct biological effects which lead to improvements in mood. Repeated use of LSD, for example, has been shown to rapidly induce down-regulation of 5HT2A receptors. Presumably, this is the brain's way of "compensating" for prolonged 5HT2A activation. This is probably why tolerance to the effects of psychedelics rapidly develops, something that's long been known (and regretted) by heavy users.

Vollenweider and Kometeris note that this is interesting, because 5HT2A blockers are used as antidepressants - the drugs nefazadone and mirtazapine are the best known today, but most of the older tricyclic antidepressants are also 5HT2A antagonists. Atypical antipsychotics, which are also used in depression, are potent 5HT2A antagonists as well.

So indirectly suppressing 5HT2A might be one biological mechanism by which psychedelics improve mood. However, questions remain about how far this could explain any therapeutic effects of these drugs. Psychedelic-induced 5HT2A down-regulation is presumably temporary - and if all we need to do is to knock out 5HT2A, it would surely be easiest to just use an antagonist...

Vollenweider FX, & Kometer M (2010). The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11 (9), 642-51 PMID: 20717121

Cats, Bins and Stalin

Britain is currently being outraged by the woman who threw a cat in a bin for some reason, and got caught on video:

As a cat person I'm as outraged as anyone, but as a vegetarian I feel that carnivores who object to this are not being very consistent. To paraphrase something that Stalin didn't actually say:

One cat in a bin is a tragedy. 2 million chickens killed every day is delicious

The life of a broiler chicken is not a happy one.