Sunday, 7 February 2010

Beware The Clam of Forgetfulness

Every day, PubCrawler emails to tell me about the latest papers that match various search terms. It means I never miss a relevant paper, but it also means I get told about an awful lot of irrelevant ones. Sometimes though, the title alone grabs my attention and demands a read. Such as yesterday's Risk assessment of the amnesic shellfish poison, domoic acid, on animals and humans. Shellfish causing amnesia?

It turns out that there's a neurotoxin, domoic acid, which can indeed cause brain damage including memory loss. It's produced by certain algae, and can accumulate inside shellfish, especially mussels.

Domoic acid is responsible for amnesic shellfish poisoning, which struck a cluster of over 100 people in Canada in 1987; 4 died, and several others suffered permanent neurological symptoms, including epilepsy and most notoriously, anterograde amnesia, the inability to form new memories.

Autopsies revealed prominent damage to the hippocampus and nearby temporal lobe areas. Domoic acid victims were therefore very similar to Henry Molaison (HM), the most famous amnesia sufferer, whose memory loss was caused by the surgical removal of the same areas.

Domoic acid is related to kainic acid, which neuroscientists will have heard of: it's widely used in epilepsy research to give animals seizures, amongst other things. Both are excitotoxins - they kill neurons by over-activating them, which opens ion channels allowing calcium to enter the cell and reach toxic levels. They're able to do this because of their chemical similarity to glutamate, the brain's most common neurotransmitter (and the one that the drug ketamine antagonizes).

Since 1987, there have been no further cases in humans, thanks to shellfish harvesting regulations. Marine animals and birds continue to suffer however, especially sea lions, although interestingly, sharks seem to be immune despite having the same glutamate receptors as mammals.

Overall, this is one more reason I'm glad to be a vegetarian. Although, that said, there are some equally nasty neurotoxins in plants...

ResearchBlogging.orgKumar KP, Kumar SP, & Nair GA (2009). Risk assessment of the amnesic shellfish poison, domoic acid, on animals and humans. Journal of environmental biology / Academy of Environmental Biology, India, 30 (3), 319-25 PMID: 20120452

Friday, 5 February 2010

Crazy Like Us

You've probably heard about Crazy Like Us, the new book by Urban Tribes author Ethan Watters. But you probably haven't bought it yet. You really should.

Crazy Like Us is a vivid, humane, and thought-provoking examination of "the globalization of the American psyche" - the process by which, slowly but surely, the world has adopted America's way of thinking about mental illness.

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The key to the American approach is the 844-page Diagnostic and Statistical Manual of the American Psychiatric Association - the DSM, or as the saying goes, the Bible of psychiatry. The heart of the DSM is a long list of disorders, each with a code number, and each with an accompanying list of symptoms: Major Depressive Disorder (296.2), Post-Traumatic Stress Disorder (309.81), Schizophrenia (295.90), etc. The DSM is more than just a catalogue of names and numbers, however; it's part a conceptual system, a way of deciding what kind of feelings and behaviours are normal, and which are pathological; it's almost a philosophy of life.

On the most straightforward level, Crazy Like Us is the story of how, over the past 20 years, this system has gone from being American to international, displacing the ways of thinking found in other countries and cultures. In four chapters, Watters describes the rise of anorexia in Hong Kong, PTSD in Sri Lanka following the 2004 tsunami, schizophrenia in Madagascar, and major depressive disorder in Japan.

This much is plain fact. The DSM is now the internationally-recognized standard for psychiatric diagnosis; almost all academic papers in psychiatry make use of the American criteria, or the extremely similar ICD-10. What's interesting, however, is Watters' account of how the DSM spread so quickly to other countries, displacing what were - in many cases - equally rich and complex local vocabularies of distress and disorder.

In the case of Japan, Watters' answer is simple: the big drug companies, in the hopes of opening a new market for SSRI antidepressants, promoted the concept of clinical depression as a common ailment, through campaigns in the Japanese media. (Japan did have an "indigenous" concept of depression, utsubyo, but it was seen as a rare, serious disease, like schizophrenia.)

But in "developing" countries, such as Sri Lanka, the picture is rather more complex. Sri Lankans were eager to learn from the West about mental illness because of their respect for Western science and technology. Americans can put people into space - surely, they know a lot about everything, including medicine, including psychiatry.

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Yet there's another level to the story of Crazy Like Us, a more interesting and more controversial one. Watters' argues that the globalization of the American way of thinking has actually changed the nature of "mental illness" around the world. As he puts it:
In the process of teaching the rest of the world to think like us, we’ve been exporting our Western “symptom repertoire” as well. That is, we’ve been changing not only the treatments but also the expression of mental illness in other cultures.
Essentially, mental illness - or at least, much of it - is a way of unconsciously expressing emotional or social distress and tension. Our culture, which includes of course our psychiatric textbooks, tells us various ways in which distress can manifest, provides us with explanations and narratives to make our distress understandable. And so it happens. The symptoms are not acted or "faked" - they're as real to the sufferer as they are to anyone else. But they are culturally shaped.


The historian of psychiatry, Edward Shorter, has written of how, in late 19th century Europe, people (mostly women) were said to be especially prone to suffering from "hysterical paralysis", but every time and place has its own shared "symptom repertoire". Culture does not just create symptoms out of thin air - there has to be some kind of underlying stress. As Watters puts it
We can become psychologically unhinged for many reasons that are common to all, like personal traumas, social upheavals or biochemical imbalances in our brains. ... Whatever the trigger, however, the ill individual and those around him invariably rely on cultural beliefs and stories to understand what is happening.
Watters links anorexia in 1990s Hong Kong to the anxiety caused by the impending transfer of control from Britain to China, a geopolitical event which caused personal worry and social disruption as people or families emigrated. But it was the high-profile 1994 case of a young girl's death from self-starvation, and the subsequent media attention paid to the Western concept of Anorexia Nervosa (DSM code 307.1), that put self-starvation into the symptom repertoire for distressed young women and led to the rise in cases.

The idea that America has exported not just concepts of illness, but illnesses themselves, is a provocative one. Is it true? Commentators have pointed out that Watters' explanation of the rise of anorexia in Hong Kong is rather simplistic. There were many social and cultural changes going on during the 1990s, most of which had nothing to do with the DSM. How do we know that increasing media promotion of dieting, and the fashion for thinness, wasn't also important? In truth, we don't, but I do not think that Watters' argument requires psychiatry to be the only force at work.

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Overall, Crazy Like Us is a fascinating book about transcultural psychiatry and medical anthropology. But it's more than that, and it would be a mistake - and deeply ironic - if we were to see it as a book all about foreigners, "them". It's really about us, Americans and by extension Europeans (although there are some interesting transatlantic contrasts in psychiatry, they're relatively minor.)

If our way of thinking about mental illness is as culturally bound as any other, then our own "psychiatric disorders" are no more eternal and objectively real than those Malaysian syndromes like amok, episodes of anger followed by amnesia, or koro, the fear the that ones genitals are shrinking away.

In other words, maybe patients with "anorexia", "PTSD" and perhaps "schizophrenia" don't "really" have those things at all - at least not if these are thought of as objectively-existing diseases. In which case, what do they have? Do they have anything? And what are we doing to them by diagnosing and treating them as if they did?

Watters' does not discuss such questions; I think this was the right choice, because a full exploration of these issues would fill at least one book in itself. But here are a few thoughts:

First, the most damaging thing about the globalization of Western psychiatric concepts is not so much the concepts themselves, but their tendency to displace and dissolve other ways of thinking about suffering - whether they be religious, philosophical, or just plain everyday talk about desires and feelings. The corollary of this, in terms of the individual Western consumer of the DSM, i.e. you and me, is the tendency to see everything through the lens of the DSM, without realizing that it's a lens, like a pair of glasses that you've forgotten you're even wearing. So long as you keep in mind that it's just one system amongst others, a product of a particular time and place, the DSM is still useful.

Second, if it's true that how we conceptualize illness and suffering affects how we actually feel and behave, then diagnosing or narrativizing mental illness is an act of great importance, and potentially, great harm. We currently spend billions of dollars researching major depressive disorder and schizophrenia, but very little on investigating "major depressive disorder" and "schizophrenia" as diagnoses. Maybe this is an oversight.

Finally, if much "mental illness" is an expression of fundamental distress shaped by the symptom pool of a particular culture, then we need to first map out and understand the symptom pool, and the various kinds of distress, in order to have any hope of making sense of what's going on in any individual on a psychological, social or neurobiological level. To put it another way, you need to understand people before you can understand psychiatry. After reading Crazy Like Us, I think I understand both a little bit better, and I strongly recommend it.

Links:
  • Ethan Watters' Crazy Like Us blog.
  • The Americanization of Mental Illness, Watters' much-read NYT article which is a fine summary of the book's argument, but being so short, misses much of the human detail which make Crazy Like Us so interesting, in particular when Watters is writing about the response of PTSD experts to the 2004 tsunami, and the life of a Madagascan woman with schizophrenia and her family.
  • Exporting American Mental Illness, an excellent discussion of the article over at Neuroanthropology.
  • Did Antidepressants Depress Japan? A 2004 article on the Japanese antidepressants and depression story.

Wednesday, 3 February 2010

Imaging the Brain Better, Faster,Thinner

A lot of the studies that I cast my Neuroskeptical eye over are related to functional magnetic resonance imaging (fMRI).This is because, in my opinion, quite a lot of today's fMRI work suffers from methodological flaws. But that's not to say that all fMRI work is suspect, or, worse, that there's something inherently unscientific about fMRI as such. fMRI's a tool, an amazing one in a lot of ways, but like any tool it needs to be used well. Along with others, I've criticized various aspects of recent fMRI practice, but only because it's frustrating to see such a powerful tool not being used to its full potential.

So I was very pleased by a recent paper by Sabatinelli et al, The Timing of Emotional Discrimination in Human Amygdala and Ventral Visual Cortex. The authors set out to test a hypothesis - that seeing an emotionally charged picture would activate the amygdala and the inferotemporal cortex (IT) before activating the extrastriate occipital cortex.

This is what should happen according to an influential model of how the brain processes emotionally meaningful information. The amygdala is part of a rapid "emotion detector" pathway, which responds faster than the standard visual perceptual system, so the theory goes. You see that it's scary before you see what it is, in other words.

To test the prediction, they scanned a single 5mm slice of the brain - see above - which cut through all of the regions of interest given the hypothesis. Most fMRI studies image the whole brain, but because scanning takes time, this produces one whole-brain image every 2 or 3 seconds.

Sabatinelli et al's single slice approach gave them 10 scans/second (TR=100ms), which was crucial given that they were concerned with detecting which parts of the brain activated first. They scanned people while showing them a series of pictures. Some were boring images with no emotional impact, some were "positive" (i.e. porn), and others were "negative" (bloody pictures of mutilation).

The results are on the left. All images activated the visual system more than a blank screen did, unsurprisingly. Both kinds of "emotional" pictures activated the amygdala, IT, and more than the boring ones did (the green line), which is reassuring, since if they didn't, the basic assumptions of the experiment would be in question. And crucially, the emotional vs. non-emotional difference occurred about up to 1s earlier in the time course of the activation in both the amygdala and the IT than in the mOcc (extrastriate occipital cortex), in line with the original predictions.

In itself, this doesn't prove the "rapid emotion pathway" model, but it's an important piece of supporting evidence. It's also a great example of the flexibility of fMRI; while it's often thought of as a way to detect where neural activation happens, as opposed to when, with the right scanning parameters, it doesn't have to be that way. Although there's an unavoidable time lag in the BOLD response that fMRI measures - the response peaks about 5 seconds after the brain cells actually fire - this doesn't stop you from investigating the relative timing of activation in different areas, as in this study.

The key was that Sabatinelli et al had a specific hypothesis and designed their experiment to test it, as opposed to just scanning people under some conditions and looking to see which parts of the brain lit up - fishing for blobs, as it's known. fMRI is a very powerful tool for blob-fishing, unfortunately. But it's also a powerful tool for doing more informative science.

ResearchBlogging.orgSabatinelli D, Lang PJ, Bradley MM, Costa VD, & Keil A (2009). The timing of emotional discrimination in human amygdala and ventral visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience, 29 (47), 14864-8 PMID: 19940182

Monday, 1 February 2010

Your Questions Answered

One of the best things about Google Analytics is that it tells you what it was that people searched for which led them to your site. Here's the top 10 search terms so far:
  1. neuroskeptic 3,973
  2. best antidepressant 3,429
  3. how to read minds 3,377
  4. why do we sleep 1,742
  5. st john's wort 903
  6. st johns wort 734
  7. st. john's wort 588
  8. legal highs 446
  9. the best antidepressant 432
  10. what is the best antidepressant 426
None of this is too surprising, although the number of people wanting to know which is the best antidepressant is a little concerning, since the short answer is that there is no one best antidepressant, because everyone responds differently to each drug. Although I've discussed research about the relative effectiveness of different antidepressants, there's still no substitute for a doctor's professional opinion.

When it comes to the bottom search terms, however, there are surprises round every corner. Here are some of the things that, curiously, only one person has yet asked.
what's is that's mean function
I don't know. Good question, though.
how to be a neuroskeptic reader
Well, reading Neuroskeptic is a good start, but you have to send me £1,000 to qualify as an official reader.
y8gvvyjjvyhktuxrym3msynmnoaszduoniu0sm81tzmwmm7ny0g1s8gyykvlmama
I'm not sure which is the bigger mystery: why did someone search for this, and why did it lead them here?
why is my wife suddenly more sexually active
She could be bipolar and entering a manic phase, or she might have started using drugs, but if were you, I'd worry about that later and enjoy it instead of Googling for explanations.
why do we sleep? describe the course of a typical night's sleep and some of the effects of sleep deprivation.
This is one of the many searches that are clearly students looking for material to plagiarise for a paper they have to write. A warning: if I ever catch a student of mine doing this, you will get an automatic F. Although I'll also give you bonus points for reading my blog, so you'll end up with a C overall.
why do the british not show emotions?
We do, but we do it in such a refined and sophisticated way that you just can't see it.
why do people die when they get stot in the head and who studies it
Hmm.
which drugs are considered dopamine agitators
Many drugs agitate dopamine - the poor neurotransmitter just can't stand to be around them. Sometimes it gets quite upset, and has to sit down and have a stiff drink when they finally leave the synapse.

Saturday, 30 January 2010

Is Depression Undertreated?

Neuroskeptic readers will be familiar with the idea that too many people are being treated for mental illness. But not everyone agrees. Many people argue that common mental illnesses, such as depression, are undertreated. Take, for example, a paper just out in the esteemed Archives of General Psychiatry: Depression Care in the United States: Too Little for Too Few.

The authors looked at the results of three large (total N=15,762) surveys designed to measure the prevalence of mental illness in American adults. I've described how these surveys are conducted before: they took a randomly selected representative sample of Americans, and asked them a standardized series of questions (the CIDI interview) about their mood and emotions, in order to try to diagnose mental illness. The interviewers, while trained, were not clinicians.

What did they find? The rate of people experiencing Major Depressive Disorder (MDD), as defined in DSM-IV, in the past year, was 8.3%. When they examined ethnicity, this ranged from 6.7% in African Americans to 11.8% in Puerto Ricans. The average severity of the depression was roughly the same in all ethnic groups.

Of those with MDD, 51% reported that they'd had treatment in the past year, either antidepressants, psychotherapy, or both. This ranged from 53% for Whites down to just 29% of Caribbean Blacks and 33% of Mexican Americans. Therapy was somewhat more popular than drugs in all ethnic groups, although a lot of people used both. However, few of the treatments were classed as "guideline-concordant", i.e. long enough to do any good, which they defined as
use of an antidepressant for at least 60 days with supervision by a psychiatrist, or other prescribing clinician, for at least 4 visits in the past year. For psychotherapy...having at least 4 visits to a mental health professional in the past year lasting on average for at least 30 minutes each.
Only 21% of depressed people were getting such treatment, even though these strike me as very lenient guidelines, especially in the case of psychotherapy - how much good is 2 hours per year doing to do?

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So depression's undertreated, especially in minorities. Too little, for too few. But this rests on an assumption: that we should treat Major Depressive Disorder.

That might not seem like an assumption, but assumptions generally don't. It seems like common sense, almost a tautology - it's a disorder, of course we should treat it! Yet it's not so simple. DSM-IV criteria for MDD require you to have 5 or more out of a list of 9 symptoms, including either depressed mood or a loss of interest in activities, lasting at least 2 weeks, and causing significant distress or impairment in social, occupational, or other important areas of functioning.

Fair enough. That's quite useful as a way of ensuring that psychiatrists in different countries are talking about the same thing when they talk about depression. But to think that depression is undertreated because only half of people meeting DSM-IV criteria for Major Depressive Disorder are being treated, is to put absolute faith in DSM-IV as a guide to who to treat. This is not what the DSM was meant to be, and there's no evidence it works for that purpose.

Is it really true that people with 5 symptoms need help, and those with 4 don't? Why not 6, or all 9? Why 2 weeks - why not 3 weeks, or 3 months? It's not as if there are loads of studies showing that treating people who have 5 symptoms for 2 weeks, and not treating people who don't, is the best strategy. I'm not aware of any such research. In particular, there's no evidence that people from the general population who meet these criteria when interviewed, but don't seek treatment, would all benefit from treatment as opposed to being left alone. Certainly some would, but they may be a minority.

This is not to say that any other criteria would be better than DSM-IV as guides to treatment, or that there is anything identifiably wrong with the DSM-IV criteria (although there is evidence that antidepressants are not useful in people with relatively "mild" MDD). The point is that doctors don't strictly apply textbook criteria when diagnosing and treating mental illness; they also use clinical judgement.

I don't know any psychiatrist who would prescribe treatment for someone solely on the basis that they met DSM-IV criteria for MDD. They would also want to know about the severity of the symptoms, whether they're related to any stresses or life events, how far they're "out of character" for that individual, etc. In general, they would deploy their training and experience to try to judge whether this person would benefit from treatment. This is why the DSM-IV carries a cautionary statement that "The proper use of these criteria requires specialized clinical training that provides both a body of knowledge and clinical skills."

So, it's far from clear that we should be treating everyone who answers interview questions in such a way that they meet DSM-IV criteria for Major Depressive Disorder. That's an assumption.

This isn't to say that everyone who needs depression treatment gets it. Sadly, there are many sufferers who would benefit from help and don't get any, or don't get it as early as they should. We need to do more to help such people. In this respect, depression is undertreated, although it's hard to know the extent of the problem. Yet it's quite possible that depression is also overtreated at the same time.

H/T Thanks to The Neurocritic for drawing my attention to this paper.

ResearchBlogging.orgGonzalez, H., Vega, W., Williams, D., Tarraf, W., West, B., & Neighbors, H. (2010). Depression Care in the United States: Too Little for Too Few Archives of General Psychiatry, 67 (1), 37-46 DOI: 10.1001/archgenpsychiatry.2009.168