June 24, 2004

Biology Links

A few interesting links, largely from Nature:

  • Mental illness, particularly depression, is on the rise in Asia. The article covers both the social issues shaping this epidemic and the difficulties of psychiatric care in Asia--not only the cultural ones (mental illness seen as a sign of weakness, different ways of expressing symptoms between Asian and Western patients) but the more interesting (to me, anyway) pharmacogenetic issues. Many psychoactive drugs (many drugs in general, really) are metabolized by the liver enzyme CYP2D6. Polymorphisms that decrease the activity of this enzyme lead to poor metabolism of drugs, which manifests as increased side effects. Asian populations have a relatively high rate of CYP2D6 alleles that are associated with poor metabolism. Unless pharmacology companies develop drugs that are better metabolized by Asian populations, psychotherapists or primary-care physicians will bear the burden of altering dosing to minimize side effects (and of ensuring patient compliance).
  • Engineering monogamy: a group studying prairie and meadow voles has found that affiliative behavior--basically, the preference of monogamy or promiscuity--can be modulated by the expression of a single gene, the vasopressin 1a receptor, in the ventra pallidum (in the forebrain) of male voles.
  • Counterintuitively, antigenic switching is most effective when the changes aren't drastic. Antigenic switching is one process by which pathogens (such as P. falciparum, the causative agent of malaria) avoid immune detection--basically, once the host has produced enough antibodies against the original surface proteins of the pathogen to clear the infection, the pathogen alters its surface proteins. In their paper, Gupta and colleagues establish a model of immune kinetics which, by considering both persistent responses to major epitopes and transient responses to minor ones, explains several previously unexplained epidemiological observations.
  • Also, as RNAi-based therapies begin to enter clinical trials, I thought I might mention a cute system I read about recently. The Sleeping Beauty (SB) synthetic transposon is a relatively new tool for gene delivery and insertional mutagenesis in vertebrate cells (transposon-based systems seem to be more common in invertebrates or plants). Some very clever researchers used SB to deliver RNA hairpins to mammalian cells, thereby creating knockdown cell lines. (The system has the overly cute name of Maleficent).

Posted by Susan at June 24, 2004 05:17 PM


Western practitioners already know that "a general rule of thumb" is that they have to lower meds dosages for people of East Asian descent, although a book I read on Culture-Bound Syndromes felt that this was too deeply entrenched in Western culture as a stereotype.

I would also disagree that depression is "on the rise" in East Asia. If you look at psychiatric syndromes world-wide, almost all diseases fall into a very few psychiatric 'taxa'--depressive disorders, anxiety disorders, dissociative disorders, psychotic disorders, etc. So while the actual diagnosis of depression may be on the rise in Asia, the prevalence of syndromes such as shenjian shuairuo in China or shin-byung in Korea has probably not changed all that much.

For me, the question is whether or not diagnosing as depression rather than shenjian shuairuo or whatever will actually have good effects. For example, a (western) psychiatrist working in Thailand had much better results when he accepted the Thai culture-bound diagnoses and traditional Thai healing models instead of trying to force it into a DSM model and psychotropic-it away.

It sickens me the way DSM treats culture-bound syndromes--a great deal of the rest of the world considers Dissociative Identity Disorder and Anorexia Nervosa to be American culturally-bound syndromes belonging to the psychiatric taxa of dissociative disorders, which appear in slightly different forms in almost every culture, and somatic/anxiety disorders, which also appear in every culture. Yet DSM legitimates our CBSs and relegates those of other culturals to some second-tier semi-legitimate oh-aren't-the-natives-quaint diagnosis.

Little rant off topic.

Posted by: Beth at June 25, 2004 09:32 AM

You make a lot of good points here, most of which I am very ill-equipped to talk about.

Regarding the validity of the "higher rate" of depression in East Asia, I would certainly agree that increased diagnosis accounts for some (much?) of it. However, the article does cite increased suicide rates as additional evidence for a higher rate of depression in China--rather, it claims that there is an increase; it supplies no data or references to support this. This is somewhat better evidence, though it could still be invalid --for one thing, it could merely reflect a change in record-keeping. A similar case can be seen with cancer in black males over the past hundred years; looking at autopsy reports, there is an apparent rise in cancer-related deaths in recent years because, previously, families had requested that "cancer" not be listed as the cause of death due to social stigma.

Back to the pharmacogenetics, with which I am much more comfortable. In this case, the patients who stand to benefit from pharmacogenetics in the short run are the minority group of normal metabolizers who are treated (initially, at least) as if they were poor metabolizers. The benefits to the poor metabolizers would come from future studies--large-scale pharmacogenetic screens to identify all of the genetic factors involved in drug metabolism, design of new drugs to circumvent these problems if possible, etc. Unfortunately, this all presupposes that we're living in some sort of happy world in which pharmacogenetics is in the clinic, which, except for a handful of cases (TPMT testing at the Mayo Clinic being one of the more famous ones) is quite untrue.

Posted by: susan at June 25, 2004 05:52 PM
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