Saturday, December 18, 2004

Reading Psychiatric News

Today's NYT contains an article about a study, originally published in Molecular Psychiatry.   The original study report  is here; the NYT article is here (permanent link).   Sometimes, when I see that something I know about has been reported in the newspaper, I wonder what it was about the topic that drew the attention of the reporter who wrote the news article.  After all, there are hundreds of medical journals, some are published every week.  Thus, there are thousands of journal articles to choose from.  Yet, only a few are deemed newsworthy. 

One would hope that reading the news article would answer the most important question: Why should I care about this?  After all, if I am going to take time away from reading blogs, and actually read a newspaper, I was to have some assurance that what I am reading is important. 

So let's give it a try, and see if this particular news article answers the question.  While we're at it, let's see if the study cited here has any other significance, perhaps something other that what the news reporter picked up on. 
Study Suggests Way to Predict Whom Antidepressants Help
Published: December 17, 2004

Scientists studying depression reported yesterday that they had found evidence that a common genetic variation affecting how people manage stress predicts how much benefit they get from taking antidepressants.

Psychiatrists have long known that about half the people found to be suffering from depression also show signs of elevated anxiety. Researchers have tried to explain the correlation, as well as why the same drugs can relieve both conditions.

In the new study, published in the journal Molecular Psychiatry, doctors from Harvard and the University of California, Los Angeles, treated with drugs a group of 54 Mexican-Americans in Los Angeles who were both depressed and highly anxious. (Limiting the study to one demographic group was a control tool.) They found that 60 percent of the group had a common genetic variant that helps govern the body's response to stress.

 The researchers found that after being treated with antidepressants, patients with the genetic variation were far less anxious and depressed than when they began the study, said the lead author, Dr. Julio Licinio of the Neuropsychiatric Institute of the University of California.

 But anxious, depressed patients who did not have the variation got much less relief from the drugs, Dr. Licinio said, adding, "This is the first time we've linked response to antidepressants to a stress-related genetic variation."
Now let's look at the study:

Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans 
Molecular Psychiatry (2004) 9, 1075-1082. doi:10.1038/sj.mp.4001587
Published online 14 September 2004
J Licinio, F O'Kirwan, K Irizarry, B Merriman, S Thakur, R Jepson, S Lake, K G Tantisira, S T Weiss and M-L Wong

There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CRHR1 genotypes with the phenotype of antidepressant treatment response in 80 depressed Mexican-Americans in Los Angeles who completed a prospective randomized, placebo lead-in, double-blind treatment of fluoxetine or desipramine, with active treatment for 8 weeks. Subjects were included into the study if they had a diagnosis of depression without other confounding medical or psychiatric diagnoses or treatments. All patients were followed weekly and assessed for changes in the Hamilton rating scales for anxiety (HAM-A) and depression (HAM-D). Inclusion criteria in the study included a HAM-D of 18 or higher. Because CRHR1 affects both depression and anxiety. Patients were classified into a high-anxiety (HA) group if their HAM-A score was 18 or higher and in a low-anxiety (LA) group if their HAM-A score was less than 18. Utilizing the haplotype-tag single-nucleotide polymorphisms rs1876828, rs242939 and rs242941, we tested for haplotypic association between CRHR1 and 8-week response to daily antidepressant treatment. In the HA group (n=54), homozygosity for the GAG haplotype was associated with a relative 70% greater reduction in HAM-A scores compared to heterozygous (63.1±4.5 vs 37.1±6.9%, respectively, P=0.002). For HAM-D, GAG haplotype homozygosity was associated with a 31% greater reduction in scores after treatment compared to heterozygous (67.3±4.3 vs 51.2±6.0%, respectively, P=0.03). In those with lower-anxiety levels at screening, there were no associations between CRHR1 genotype and percent change in HAM-A or HAM-D. These findings of increased response to antidepressants in highly anxious patients homozygous for the GAG haplotype of CRHR1 need to be independently validated and replicated. Such work would support the hypotheses that response to antidepressant treatment is heterogeneous and that the CRHR1 gene and possibly other genes in stress-inflammatory pathways are involved in response to antidepressant treatment. These findings also suggest that variations in the CRHR1 gene may affect response to CRHR1 agonists or antagonists. All data are deposited in www.pharmgkb.org.
The newspaper article states that the study "Suggests Way to Predict Whom Antidepressants Help."   The abstract of the article says no such thing.  In fact, the methodology of the study would not permit such a conclusion.  Granted, the newspaper article did not say that the researchers had found something clinically useful; rather, the author stated that the study "suggests" it.  The newspaper article quotes the lead author as having said "This is the first time we've linked response to antidepressants to a stress-related genetic variation."  OK, I guess that is a "suggestion," but it is no more than that. 

Actually, this is not the first time that researchers have found some kind of biological marker that could someday be used to predict antidepressant response.  All the the others have failed to generate anything clinically useful, though.  They all have been interesting, but only to researchers.  None has been particularly newsworthy, with regard to the average citizen. 

Is there any  reason for this study to have been reported in the New York Times?  Perhaps.  But if so, it is not for the reason cited in the newspaper article.  The fact is, the study by Licinio, et. al., is important only in the context of the entire body of scientific literature that demonstrates biological markers for mental illness.  Just as a single fossil doesn't really mean much, a single study in a biological psychiatry journal does not mean much.  It is only when you look at what all the studies add up to, that any meaning emerges.

There have been many studies that demonstrate conclusively that there are detectable, quantifiable abnormalities in the anatomy and physiology of persons with mental illness.   The shear volume of studies pretty much forces the conclusion that there is something wrong with the anatomy and physiology or these patients.  It does not say anything directly about the causes of the the conditions.  So far, it does not say much about the treatment, either.   Of course, if we could  say something about causes or treatments, that would be newsworthy.  People, in general. tend to be curious, even eager, to learn about matters of practical significance.  The Licinio study does not meet that criterion.  It has no practical significance.  Rather, the significance is a philosophical and social one. 

In a social context, a person who chronically functions poorly tends to be judged, even stigmatized.  However, if there is some kind of demonstrable biological marker -- say, a blood test or a brain scan -- that is abnormal, then the tendency is to treat the person with a bit more compassion.  This does not make any sense, of course, but it is true.  Most value judgments serve no useful purpose, but it seems inevitable that humans go around making such judgments of others. 

Thus, the significance of the finding -- of objective biological markers -- is that it might, someday, lead to a reduction in the frequency and severity of these senseless judgments.  That would make the world a better place.

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