Depression Tests: When “Basic” Research Becomes “Applied”

April 22, 2012

Anyone with an understanding of the scientific process can appreciate the difference between “basic” and “applied” research.  Basic research, often considered “pure” science, is the study of science for its own sake, motivated by curiosity and a desire to understand.  General questions and theories are tested, often without any obvious practical application.  On the other hand, “applied” research is usually done for a specific reason: to solve a real-world problem or to develop a new product: a better mousetrap, a faster computer, or a more effective way to diagnose illness.

In psychiatric research, the distinction between “basic” and “applied” research is often blurred.  Two recent articles (and the accompanying media attention they’ve received) provide very good examples of this phenomenon.  Both stories involve blood tests to diagnose depression.  Both are intriguing, novel studies.  Both may revolutionize our understanding of mental illness.  But responses to both have also been blown way out of proportion, seeking to “apply” what is clearly only at the “basic” stage.

The first study, by George Papakostas and his colleagues at Massachusetts General Hospital and Ridge Diagnostics, was published last December in the journal Molecular Psychiatry.  They developed a technique to measure nine proteins in the blood, plug those values into a fancy (although proprietary—i.e., unknown) algorithm, and calculate an “MDDScore” which, supposedly, diagnoses depression.  In their paper, they compared 70 depressed patients with 43 non-depressed people and showed that their assay identifies depression with a specificity of 81% and a sensitivity of 91%.

The other study, published two weeks ago in Translational Psychiatry by Eve Redei and her colleagues at Northwestern University, purports to diagnose depression in adolescents.  They didn’t measure proteins in patients’ blood, but rather levels of RNA.  (As a quick aside, RNA is the “messenger” molecule inside each cell that tells the cell which proteins to make.)  They studied a smaller number of patients—only 14 depressed teenagers, compared with 14 non-depressed controls—and identified 11 RNA molecules which were expressed differently between the two groups.  These were selected from a much larger number of RNA transcripts on the basis of an animal model of depression: specifically, a rat strain that was bred to show “depressive-like” behavior.

If we look at each of these studies as “basic” science, they offer some potentially tantalizing insights into what might be happening in the bodies of depressed people (or rats).  Even though some of us argue that no two “depressed” people are alike—and we should look instead at person-centered factors that might explain how they are unique—these studies nevertheless might have something to say about the common underlying biology of depression—if such a thing exists.  At the very least, further investigation might explain why proteins that have no logical connection with depression (such as apolipoprotein CIII or myeloperoxidase) or RNA transcripts (for genes like toll-like-receptor-1 or S-phase-cyclin-A-associated protein) might help us, someday, to develop more effective treatments than the often ineffective SSRIs that are the current standard of care.

Surprisingly, though, this is not how these articles have been greeted.  Take the Redei article, for instance.  Since its publication, there have been dozens of media mentions, with such headlines as “Depression Blood Test for Teens May Lead To Less Stigma” and “Depression Researchers May Have Developed First Blood Test For Teens.”  To the everyday reader, it seems as if we’ve gone straight from the bench to the bedside.  Granted, each story mentions that the test is not quite “ready for prime time,” but headlines draw readers’ attention.  Even the APA’s official Twitter feed mentioned it (“Blood test for early-onset #depression promising,” along with the tags “#childrenshealth” and “#fightstigma”), giving it a certain degree of legitimacy among doctors and patients alike.

(I should point out that one of Redei’s co-authors, Bill Gardner, emphasized—correctly—on his own blog that their study was NOT to be seen as a test for depression, and that it required refinement and replication before it could be used clinically.  He also acknowledged that their study population—adolescents—are often targets for unnecessary pharmacological intervention, demanding even further caution in interpreting their results.)

As for the Papakostas article, there was a similar flurry of articles about it when preliminary results were presented last year.  Like Redei’s research, it’s an interesting study that could change the way we diagnose depression.  However, unlike Redei’s study, it was funded by a private, self-proclaimed “neurodiagnostics” company.  (That company, Ridge Diagnostics, has not revealed the algorithm by which they calculate their “MDDScore,” essentially preventing any independent group from trying to replicate their findings.)

Incidentally, the Chairman of the Board of Ridge Diagnostics is David Hale, who also founded—and is Chairman of—Somaxon Pharmaceuticals, a company I wrote about last year when it tried to bring low-dose doxepin to the market as a sleep aid, and then used its patent muscle to issue cease-and-desist letters to people who suggested using the ultra-cheap generic version instead of Somaxon’s name-brand drug.

Ridge Diagnostics has apparently decided not to wait for replication of its findings, and instead is taking its MDDScore to the masses, complete with a Twitter feed, a Facebook Page, and a series of videos selling the MDDScore (priced at a low, low $745!), aimed directly at patients.  At this rate, it’s only a matter of time before the MDDScore is featured on the “Dr Oz Show” or “The Doctors.”  Take a look at this professionally produced video, for instance, posted last month on Youtube:


(Interesting—the host hardly even mentions the word “depression.”  A focus group must have told them that it detracted from his sales pitch.)

I think it’s great that scientists are investigating the basic biology of depression.  I also have no problem when private companies try to get in on the act.  However, when research that is obviously at the “basic” stage (and, yes, not ready for prime time) becomes the focus of a viral video marketing campaign or a major story on the Huffington Post, one must wonder why we’ve been so quick to cross the line from “basic” research into the “applied” uses of those preliminary findings.  Okay, okay, I know the answer is money.  But who has the authority—and the voice—to say, “not so fast” and preserve some integrity in the field of psychiatric research?  Where’s the money in that?

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