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

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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46 Responses to Depression Tests: When “Basic” Research Becomes “Applied”

  1. aek says:

    You bring up many important aspects in this post. I hope that Gary Schwitzer, Carl Zimmer and other key science reporters and bloggers take this and run with it (although it has more sharp points than scissors.)

    One aspect that hasn’t had much coverage is the use of science reportage and science blogging as free marketing for those who are in positions to benefit from the profit and commercialization side of research findings. I was (naively) shocked the first time I realized that reporting was cut and pasted from PR offices’ press releases. Now, unless I do time consuming due diligence, I still have problems in determining what comes directly from the findings and is legitimate and what is spun. The general public? Sales, sales, sales.

    In this particular example, I wonder how the profiteers will manage to evade liability when “MDD” customers suffer as a direct result of this malfeasance. And where people who are in distress can find legitimate, safe and effective help to lessen distress and address causative distressors.

  2. Jaen Wirefly says:

    It’d be nice to have medical proof of psychiatric illnesses for many reasons: easier insurance reimbursement, less stigma, psychological validation. However, I don’t see how a blood test to determine brain functioning is possible. Plus, if you’re already on psychotropic meds wouldn’t this skew the results?

  3. Bernard Carroll says:

    The chutzpah in these two claims is stunning. So is the mindless empiricism of the methods. It might be nice to have a biomarker with some connection to the actual biology of depression. It might be nice to have a non-secret methodology. It might be nice to have a respectable sample size. It might be nice to study the disorders at the boundaries of major depression. It might be nice to know whether these are enduring trait markers or episode-related state markers. It might be nice to know whether common drugs or medical conditions invalidate the tests, and on and on.

    But, hey, when you can charge $745 for this pos and get away with it, why bother with those pesky issues? Papakostas at Harvard-MGH seems to be a KOL front man for Ridge Diagnostics, just like Nemeroff was for Glaxo. To judge by the video, the Ridge Diagnostics crew should be shunned.

    You ask, who has the authority—and the voice—to say, “not so fast” and preserve some integrity in the field of psychiatric research? There was a time when journal editors understood their fiduciary responsibility in this regard. But that was in the past.

  4. Tom says:

    What’s the point of this research? Less stigma? Hey– I am sure there are biomarkers for Elephant Man’s Disease but the stigma remains the same. As for the blood test itself? Let’s imagine an a adolescent telling a doctor that he or she is suicidal and depressed and about to jump out the window. Can the doctor reply: “Hey don’t worry, your blood test came back normal and you are not depressed?” I don’t think so! And vice versa. Oh… and can we please have some replication before the press gets involved, not to mention before companies start selling this snake oil?

    • Anonymouus says:

      Exactly! Please all psychs and researchers in the field, try not to talk out of both sides of your mouth. We need to not condemn research, efficacy and an effort for progress in the field. There is. I have seen it! It is now funded by private dollars and I do not have a porblem with that. Stuff that is going nowhere and is someone’s thesis is BS and over enthusiasm published before being extremely vetted belongs in the circular bin. Please do not blame anyone for trying toake a buck, the temptation is great and lu\\lucrative incrative. I do not personally

      fund big pharma or mediocriry and repetiveness in Univeristies. There are too many in the field that actually care. If you keep pulling up the keel the boat will tip…I have been there. Sometimes you learn the hardway and get pretty teed when you hear this is, in, the true sense of those that wish, to heal, or make head-way in research, is frankly silly. We all need to think of those really afflicted and think everyone is on the same page, putting a consensus together, I have found to be impossible. But refuse to give up…just care too much!

      s the have

    • Denise B says:

      I thought the issue here was that the test is way premature to be used clinically. You seem to be objecting to a test in theory even if a good one could be developed.

      As a patient I would welcome such a test as a great improvement over having to come up with answers to meaningless questions like “on a scale of 1 to 10, how helpless do you feel?”.

  5. Terri says:

    I’m with you Tom as what’s the point when the patient is depressed, clinically depressed and it’s interfering with work, love and play enough to come see me. Patients don’t want to see me they only come when they are really struggling. A test???? what’s the point-it is what it is and we need to get the patient to exercise, meditate, yoga, mother nature and of course they probably are unable to do these things because they are DEPRESSED. SO WE MOVE To the next intervention meds. The patients can barely afford coming to an appt and securing the meds much less get a test. The wealthier patients definitely want the test so they can feel okay about their depression. What’s wrong with this picture–again it is what it is—feel okay about it, get it treated and move on with your life at this point in time with the research.

  6. Altostrata says:

    “But who has the authority—and the voice—to say, “not so fast” and preserve some integrity in the field of psychiatric research?”

    It won’t be Thomas Insel at NIMH, that’s for sure.

    I really don’t understand how they get from the blood of specially bred rats to a diagnosis of depression in teenagers. How did they verify depression in the rats? Diagnosing depression from rat behavior — a tad excessively anthropomorphic? Maybe the rat has indigestion!

  7. mara says:

    It sounds like this is the new Spect scan (only with blood). Hmmm. I don’t know how I feel about this. I don’t blame people for buying into this.

    Disproving “somatoform disorders” would be a good reason to want it. If someone had powerful physical symptoms and was having trouble getting doctors to run tests because of the MDD label, then I could see why they would want the test in order to disprove MDD.

    There are plenty of reasons to want the test. Depression is an illness like any other illness, and a blood test could give it more credibility. But I do wonder…What if we found a gay gene? What if we could prove beyond any shadow of a doubt that homosexuality is not a choice, and homosexuals cannot help feeling attracted to the same sex. Would that make homophobes any less homophobic? Are people who discriminate against the mentally ill going to be any less discriminatory with an MDD blood test available? Even people who believe homosexuality is biological argue that gay people can always choose not to give into their urges. They choose to engage in homosexual acts. I would think they would do the same thing for Depression. They choose not to go out and have fun! They choose to not smile! Yes there is a biological cause predisposing them to Depression, but they could always choose to fight their depressive urges and be happy anyway.

    For example, I’m pretty sure we have established that dyslexia is real. But look how everybody hammered George W. Bush. And I know he said he’s not dyslexic, but really…I’m pretty sure he’s dyslexic. What about addiction? That’s an illness. If we had a blood test for alcoholism would that really reduce stigma.

    • Peter C. Dwyer says:

      Mara,

      You state, “Depression is an illness like any other illness,”

      Are you a scientist? A medical doctor? If so, you deal in scientific proof. So, about your statement:

      Prove it.

      Depression lacks much of what other “illnesses” have: known cause, known pathophysiology, known physical diagnostic tests, verified mechanisms of how treatment works (IF it works) … So why are you so sure that “depression is an illness like any other illness,” – why do you feel so confident of this that you offer your statement without troubling yourself to support it?

      These days even many die hard advocates of bio-psychiatry and PhARMA admit nobody knows what causes depression.

      I never understood why those who say the evidence so far does not persuasively show “mental illness” to be biologically caused, are accused of downplaying the suffering involved. Clearly, many people are fighting desperately for their lives; but there is still no convincing evidence that “mental illness is an illness just like other illnesses.”

      You stress stigma. Bio-psychiatry has not appreciably changed that. We don’t need biological causes to take a stand against stigma – just say flatly that hating, shunning, belittling, discriminating against, blaming are not how humans should be treating each other.

      The best way to combat stigma is with visibility, person to person contact, relationships. Now Dick Chaney favors gay marriage, most likely because someone he loves – his daughter – is gay.

      • herb says:

        Dear Mr. Dwyer,

        I think you’re splitting hairs needlessly. Here are several definitions of the word “illness”.

        illness /ill•ness/ (il´nes) disease.
        ——————————————————————————–

        emotional illness a colloquialism for mental disorder, but not usually including mental retardation or mental disorders with a specific, known, organic etiology.
        mental illness see under disorder.

        Dorland’s Medical Dictionary for Health Consumers. © 2007 by Saunders, an imprint of Elsevier, Inc. All rights reserved.

        ——————————————————————————–
        ill•ness (lns)
        n.
        Disease of body or mind; poor health; sickness.

        The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.

        ——————————————————————————–
        illness
        Etymology: ME, unhealthy condition
        an abnormal process in which aspects of the social, physical, emotional, or intellectual condition and function of a person are diminished or impaired compared with that person’s previous condition.
        Mosby’s Medical Dictionary, 8th edition. © 2009, Elsevier.

        http://medical-dictionary.thefreedictionary.com/illness

        I’m not a scientist or medical doctor but on the other hand I am a long-time support person and health care advocate.

        At the moment there are no diagnostic tools to justify depression but the same holds true for a number of neurological illnesses. As an example would you deny the existence of Parkinson’s or PSP or any number of neuropathies as an illness based upon your statements. I’m similarly reminded of a serious bout I had with Plantar Fasciitis as another example of illness you would seem to deny exists but I could attest to it both being painful and debilitating without there being any diagnostic tests.

        Whether or not you call depression an illness, disorder or disease etc. does not diminish the suffering and anguish experienced by the individual. The fact we are lacking definitive quantitative diagnostic means at this very moment to scientifically establish the existence of this illness is certainly perplexing to me and only means we have a greater need for continuing research.

        I am also reminded of reading similar statements to yours in the field of astronomy. As research equipment improved so too have the observations of heavenly bodies formerly denied now come into prominence. Astronomy has yet to picture a black hole yet from observations, calculations and theory one is led to the existence of such a phenomenon. I am one who happens to believe that in time and with better equipment and continued research that many of the severe mood illnesses/disorders/behavioral issues will be shown to have some neuro-biochemical basis of brain malfunctioning.

        I would therefore base upon definition agree with Mara; “Depression is an illness like any other illness,”

        Warmly,
        Herb
        vnsdepression@gmail.com
        http://www.vnstherapy-herb.blogspot.com

      • mara says:

        “Depression lacks much of what other “illnesses” have: known cause, known pathophysiology, known physical diagnostic tests, verified mechanisms of how treatment works (IF it works) …”

        I am not a scientist or medical doctor. But like I said…I’m pretty sure dyslexia is also a real medical condition with a biological cause. There is no known cause for it. No known pathophysiology, physical diagnostic tests, or verified mechanisms of how treatment works. But I’m still pretty sure it’s a real medical condition. That goes for every other learning disability. There’s no test for LD except IQ testing and achievement tests. However, we do know stimulants and (from what I’ve heard) statin drugs can help. I don’t know that we have any clue why they work in people with LD but they do. Why the heck do you think 60% of all people diagnosed with ADHD are also LD? School systems want these kids on Ritalin, because they’ve seen kids with dyslexia and other forms of LD getting big boosts in IQ (to the point that they are no longer considered LD). But you can’t give stimulants for LD, so that would require an ADHD diagnosis. I really don’t think it’s a coincidence that there is such a high number of ADHD people who are also LD. I don’t know if ADHD causes LD or LD causes ADHD. Or if they just happen to go together quite often. Either way, there is evidence to support LD is biological in nature, it often responds to stimulant use and special education, and we have no clue why.

        I don’t know anyone who still thinks LD is not a biologically based medical condition. And there is no physical proof it exists. When I was in school in the 90s/early 2000s they thought is was caused by mental illness :/ And that was as late as 2004. Like I was scared to report it when I went to college, because I thought they would try to link it to mental illness. But then I saw they had little pamphlets saying that LD is not caused by mental illness, and I felt better about it. They still thought it was biological, but they thought it was separate from ADHD and other mental illnesses. LOL that they felt they actually had to have a pamphlet explaining that LD is not caused by mental illness.

        I mean…I don’t have evidence for biological causes for the LDs. And I don’t have it for the mental illnesses either. But everything in me screams….it’s biological!

        And I actually agreed with you…I’m not convinced finding a physical cause will reduce stigma. I feel like I highlighted that pretty well. Lot’s of people believe in dyslexia as biologically based, but people were still mocking George W. Bush. The same goes for homosexuals and drug addicts. I don’t think finding physical causes for those things would reduce stigma either. The types of people who don’t like George W, or homosexuals, or drug addicts, are going to continue to act like that regardless of evidence of a physical cause.

        When I found out about brains scans to detect LD, I was pretty excited. Finally! Proof! But really…what is that going to change? LD people are like 5% of the population and something like 20% of welfare recipients and 20% of prison inmates. It’s how to work with it that is the issue. The same goes for the mental illnesses. Lots of people are convinced, deep down, that there is something very biological happening in these people. But it’s not about proving what caused it. It’s more about how we deal with it. There should be less stigma attached to things like mental illness and LD. I don’t know that this will be lessened by any of the fancy testing people are talking about.

      • Altostrata says:

        Mara, because a drug changes behavior does not mean that behavior is a biologically based disease. And that goes for VNS, too, Herb.

        I am one who believes there is no neurophysiological basis for mood disorders, as mood disorders are defined now, except that they occur in the body and nervous system just like everything else included in what we call consciousness.

        You and Herb are using the term “depression” very loosely. It could mean anything. Thus, there is nothing to discuss, it’s all spinning wheels.

      • herb says:

        Altostrata,

        Thank you. I never stated that drugs or VNS changing behavior means that behavior is a biologically based disease. Although, it is an interesting observation in my experiences as to what has and has not benefited my spouse.

        Almost 5 decades as a support person and health care advocate to my spouse who suffered from major depression for 36 years with 9 suicide attempts; I don’t think I use the word depression in my spouse’s cases history “loosely”. In fact, I used it specifically. These past 12 years with the use of a neuro-modulation therapy has been remarkable. To add to the fact, we no longer use or have need to discuss her depression as it no longer exists or affects our lives.

        As for spinning my wheels, I’d opine that the absence of my spouse’s depression with her current therapy and without the use of psychotropic medications for her depression is anything but “spinning wheels”, at least in our experiences. It was all about finding efficacy, stabilization and remission. Consciousness; hmmm, never gave it one thought.

        I’ll leave you to your “consciousness” thoughts by only adding that serious depression is the only illness which to the best of my knowledge goes against nature’s very basic instinct for survival.

        Warmly,
        Herb
        vnsdepression@gmail.com
        http://www.vnstherapy-herb.blogspot.com

    • mara says:

      To explain to Altostrata, I am referring to MDD when I talk about depression. The you tube ad said the test was for MDD specifically. I don’t mean subclinical depression or, god forbid, grief. Listening to someone talking about testing for grief and medicating it would be too much for my ears to listen to. And it’s true that medication effectiveness does not prove a biological cause…but that aside…something just feels biological about all of this. My feeling are not scientific. MDD just feels biological. For instance, I was watching a friend go through withdrawal from an antidepressant. And what she was going through was not a natural mood state. There was obviously something biologically off with her, and I could tell it was a withdrawal syndrome the second she told me she discontinued her meds. This was not just a spiritual crisis. I felt like her biology was all out of wack.

      It’s like the muttations from The Hunger Games series. In the second book they bring out the monkey “muttations”. A muttation is an genetically engineered animal that is a “mutt” because it is a cross between a real animal and a genetically engineered one. At first the monkey “mutts” just look like regular monkeys, but then the monkeys start going crazy and try to hunt and kill all the people in the game. And the people realize that the monkeys were mutts because animals in nature do not behave like that. I don’t know if you have ever seen a person having a psychiatric event and your first thought was, “This is not God’s will. This is something else.” That is how I felt with my friend when she withdrew from her meds. It was some weird “muttation” of depression. That kind of depression needs to be engineered by a pharmaceutical company in order to exist. However, if you witness something like that in someone NOT withdrawing from a med, that to me is still like a “muttation.” It may not be genetically engineered by people, but it’s like a cross between an actual mood that you can find in everyone and some other unnaturally severe mood disturbance that does not belong in nature. MDD is like a muttation, and that’s why it feels biological to me. It feels like a mood anyone could have, but it’s been unnaturally engineered to be far worse and against whatever laws of nature God laid down.

  8. Anyone remember the dexamethasone suppression test in the 80′s? I do. All the psychiatrists were giving it to their depressed patients to “prove” they had a “real” disorder.

    Trouble was, it didn’t predict which depressed patients would benefit from an antidepressant and who would not, or when patients who did benefit could safely stop the medication. Number of doctors using it in depressed patients now? Must be pretty close to — none.

  9. Bernard Carroll says:

    There is an interesting new book about the dexamethasone suppression test, written by Edward Shorter and Max Fink, with the title Endocrine Psychiatry. They tell the story of how the test rose and fell in clinical use as a biomarker of melancholia.

    To Dr. Allen’s points, the DST does have clinical significance. A positive DST signals a low rate of response to non-drug treatment of depression; it signals high risk of relapse if it does not convert with treatment; it signals an 8-fold increased risk of switch from unipolar to bipolar depression; it signals an 8-fold risk of completed suicide on follow-up; and it signals a high probability of diagnostic revision from boundary conditions like schizophrenia or adjustment disorder to depression on follow-up.

    • Hawkeye says:

      To Bernard Carroll,
      This is a friendly question, why is the dexmethasone suppression test not used?
      I am writing this from memory, so may be missing some subtilty: the test above reminds me of a paper of William Coryell et. al. which seems to demonstrate clearly that biopolar depression can be distinguished from unipolar depression by the fact that the first degree relatives of bipolar depressed patients are high achievers. A stunning result which seems to have been lost:

      “Bipolar Affective Disorder and High Achievement: A Familial Association.” Am. Jour. of Psychaitry. Aug. 1989

    • Dr. Carroll (and Hawkeye),

      You are right. A positive DST test does have significance in terms of increasing or decreasing the ODDS of certain phenomena, and it does show that there is a high likelihood of a significant biological component to major depression.

      The reason it’s not used, however, is that a positive or negative DST does not tell us much of anything about how an INDIVIDUAL will respond to treatment. And therein lies the problem with biomarkers in psychiatry.

      A biopsychosocial clinical profile of the patient is a far better predictor of treatment response than any blood tests, at least so far.

      • Hawkeye says:

        Dr. Allen says:

        “The reason it’s not used, however, is that a positive or negative DST does not tell us much of anything about how an INDIVIDUAL will respond to treatment.”

        Bernard Carroll seems to say the opposite.

        Probablistic models are perfectly usable aids to thinking. Would you assert that if you roll one fair die and would like to roll a six, the fact that there are six different numbers on the die has no bearing on predicting the outcome of your INDIVIDUAL role?

    • Hawkeye says:

      To Bernard Carroll:
      Bought the book. My doctor talks about cortisol. My before coffee mood is horrific, he says that this is because of sharply rising cortisol levels. I will put the book under my pillow and hope for the best.

    • Hawkeye says:

      To Bernard Carroll:
      Endocrine Psychiatry was wonderful, not only the science but the tale of how the science was done. You would have made a great Sydney cab driver.

      There is something profoundly, profoundly biological driving what we call depression, and symptom checks aren’t getting at it. I suspect that this is because psychiatrists don’t know how to use them.

      Is it possible that doctors are so alien from Baysian reasoning? If a doctor comes home and finds his front door open, his dog on the lawn and his burglar alarm going off doesn’t he say “The contitional probability that my house has been robbed is……..”
      There is no Baysian statistics, there is common sense.

  10. Tom says:

    Yeah I didn’t realize that this blood test has the potential for differentiating rodent depression in adolescents from normal teens. Ok let’s market it now!

  11. Bernard Carroll says:

    @ Dr. Allen, if you frame the questions differently there are situations where a biomarker result may influence the treatment of an individual patient. For instance a depressed patient who tests positive on the DST would not be a good candidate for elective treatment with psychotherapy alone. In terms of drug response, a positive result is associated with a high drug versus placebo difference in rate of response (NNT around 2) whereas a negative result is associated with a much lower drug versus placebo difference in rate of response (NNT around 10). But you are correct in saying that if you were to treat every depressed patient with an antidepressant drug then the test result would not predict eventual response. The test result is associated only with so-called specific drug response. Another instance of the test influencing management of an individual patient would be where there is apparent improvement with drug treatment but an initially abnormal test has failed to normalize. Stopping the drug in that situation would not be advisable.

    @ Hawkeye, thanks for your question. The book Endocrine Psychiatry that I mentioned gives a good account of the history. I would say two main reasons were the de-emphasis of melancholia in DSM-III-IV and the realization that plasma dexamethasone levels also were needed as well as plasma cortisol for test interpretation. If you look at the data it is clear that biomarkers like the DST and short REM sleep latency perform at least as well as the symptoms that are used for diagnosis of major depression.

    • Altostrata says:

      Perhaps distinguishing true MDD became unimportant because it became widely assumed antidepressants were safe and good for everyone. Throwing an antidepressant prescription at any patient for whatever reason — and calilng it “depression” — has been much easier and cheaper than going through the tedious process of differential diagnosis.

      It’s only recently. since Kirsch stratified antidepressant efficacy, overall that MDD has become the focus again of depression treatment.

    • Dr. Carroll, I can almost always tell which depressed patients are unlikely to respond to a psychotherapy alone with a good clinical evaluation. But yes, if you just use a “symptom checklist,” that wouldn’t be as good as a DST test.

      Also, I haven’t really kept up with it, but I was under the impression that an abnormal DST did not necessarily normalize with treatment. Do you have a reference that says otherwise, by any chance? Thanks.

      • Bernard Carroll says:

        Dr. Allen, there are a great many caregivers who do not share your confidence on that point. For your other question, here is a reference. Thanks for your interest.

        Dexamethasone suppression tests in antidepressant treatment of melancholia. The process of normalization and test-retest reproducibility.

        Greden JF, Gardner R, King D, Grunhaus L, Carroll BJ, Kronfol Z.

        Arch Gen Psychiatry. 1983 May;40(5):493-500.

        PMID:6340634

      • herb says:

        Dr. Allen,

        Dr. Carroll brings up an interesting point of view.

        I am a caregiver and acknowledge other physicians and psychologist with whom we’ve collaborated making a similar determination after “a good clinical evaluation”.

        Maybe you’d care to further elaborate upon and define what you consider “a good clinical evaluation” to aid in your determinations?

        Warmly,
        Herb
        vnsdepression@gmail.com
        http://www.vnstherapy-herb.blogspot.com

      • Herb, that’s a big question. A complete biopsychosocial evaluation used to be taught routinely in psychiatry residencies, but much less so today.

        Obviously, it helps to be an experienced psychotherapist yourself, so one can recognize the difference between acting out and other types of psychiatric and psychological symptoms, as well as have an understanding of what psychological and social factors influence symptom presentation.

        I discuss some of the elements of a BAD psychiatric evaluation at http://www.psychologytoday.com/blog/matter-personality/201204/how-recognize-bad-psychiatrist

      • Altostrata says:

        Great article, Dr. A. More doctors should speak out like that. Your commenters are lovin’ it.

      • Hawkeye says:

        I read your article. I agree that the magazine you discuss is suspect as are its contents.

        Otherwise I think you are wrong: it is very highly likely indeed that bipolar II, however ill understood and exploited, corresponds to a true reality, and is mostly about mixed states. Dr. Ronald Pies has written much about how psychaitry is really a medical science, like many others, with a level of uncertaintly that approaches those of other disciplines.

        I will leave the discussion to the experts, and say only that mood stabilizer mono therapy after years of horrific treatment with antidepressants was a miracle in the life of a friend and remains so.

        To be sympathetic, I cannot understand why Big Pharma is promoting Bipolar II. Mood stabilzers are generic, and the option of no treatment is a vialble one. The real issue is not the diagnosis of Bipolar Spectrum Disorder but its treatment, and the first line treatment for a lot of bipolar disorder involves a psychotropic drug–alcohol. How much Bipolar II symptomotology is just glutamate rebound and GABA supression because of drinking seems to be an interesting question.

        Further, a lot of folks seem to think that Bipolar disorder is a metabolic disease, so why one would routinely prescribe metabolically disruptive medications like atypicals to treat it is beyond my understanding.

        I am not a doctor, but I have an option that perhaps most practitioners don’t have, acess to all important psychiatric journals. It is an interesting trade off.

      • Altostrata says:

        Hawkeye — Mood stabilizers can be helpful for iatrogenic damage from antidepressants, which often includes symptoms such as hyper-alerting, sleeplessness, and over-the-top anxiety, and possibly akathisia.

        Just because a so-called “mood stabilizer” seems to lessen symptoms doesn’t mean the underlying disorder is any variety of bipolar!! (“Mood stabilizers” originally treated epilepsy.)

      • Hawkeye says:

        Alto,
        Good point. I also worry a lot about the long term damage that may be done by atypicals.
        I do not understand how it is that psychiatrists balance risk and reward. This is not their business, it is the business of the fully informed patient.

      • Altostrata says:

        I disagree. It IS the doctor’s business. It’s because so many doctors don’t know what they’re doing with these drugs that patients need to practice “defensive medicine.”

      • Hawkeye says:

        It is the doctor’s business to be able to asess risk and reward. Yes, doctors cannot or will not do this. So for whatever reason it has become the patient’s business to practice defensive medicine.

        I think this permeates all of American Society. We are trusting experts, in finance, education, politics who don’t know what they are doing. The reason they don’t know what they are doing I suspect is that human knowledge at its base is just not good enough to give us the answers we want.

        One reason that psychiatric treatment seems, but may not be, especially poor, is that psychiatric patients have little money. If psychiatric disease had an age of onset of about 55 and hit upper middle class people hard, the 15 minute med check might disappear.

      • Altostrata says:

        Hawkeye, what is the basis of your assumption that most psychiatric patients have little money?

      • Hawkeye says:

        Serious psychiatric disease is debilitating and has early onset. I am assuming that this keeps people so afflicted from being successful in the job market. I am talking about serious disease.

        I apolgize if this seemed discriminatory. I would say the same thing about people with epilepsy or chronic heart disease.

        In any case, Barbara Erhenreich’s “Bright Sided” tells a story of how upbeat you must be positive, positive positive to succeed in America.

      • Altostrata says:

        Working people who have health insurance also get psychiatric diagnoses and psychiatric drugs. To the rest of the world, they are also psychiatric patients. There are about 30 million people in the US on antidepressants, about 3 million on antipsychotics.

        Those on antidepressants are also short-changed by the system, sometimes to the extent that their supposedly less risky regimens are disabling. However, I would not make the generalization that psychiatric patients form a lower rung of society economically. They are a cross-section of society.

      • Hawkeye says:

        Alto,
        Good point. It falls within my experience that functioning people have their lives destroyed by anti depressants.

        An idea I keep in my head:
        a law student starts having problems at 23, is made worse by psychiatry and then at 28 realizes that she has been messed up more by medicine than by disease. Perhaps a life is straightened out, now explain that to the law school, same for business, or any other enterprise. Fully recovered patients not only lose economically for the duration of their disability but also—-well, forever. “There is a tide in the affairs of men which when taken at the flood…..” Shakepeare. You must take your tide at the flood.

        I get upset with Whittaker because his “gotcha” attitude can turn neutral people off, but basically, not completely at all, but basically he is probably right.

      • herb says:

        Dear Doc Allen,

        Thanks for your response and the heads up on the link to your article.

        I don’t believe I asked “a big question” but I can assure you it is a most serious question not only from my vantage point but for prospective patients and/or their support people when enlisting the help of a specialist in this field and for which I do appreciate your thoughts and concerns as illustrated in your writings.

        I prefer in my historical commentaries to refer to doctors in this specialization as doctors, good doctors and better doctors and your article being a reasonably good starting point for the un-initiated to seek out the better doctors. I can say from our experiences that we have been fortunate in my opinion to have collaborated with a number of better doctors.

        On the other hand I’m somewhat different after being a support person for so many years. When having need for a new psychiatrist our initial visit consists more of interviewing the physician and his/her philosophies and practices before we even get down to discussing my spouse and her case history. From your writings I am reminded of an anecdotal incident in which we had needed to enlist a new psychiatrist to attend to my spouse’s current treatment. After my spouse spent three-quarters of hour in the doctor’s waiting room filling in his lengthy questionnaire we were then seated in his office. I proceeded to ask him if he knew anything of her treatment and would be interested in attending to and modulating her newest treatment and that I would make arrangements to have him trained. He responded that “he wasn’t interested in learning something new” at which point I interrupted his narrative and asked my spouse to please get up and we left his office. The visit was under 3 minutes which was the incredible shortest visit we ever had with any physician. I shall point out this physician was recommended to us by a friend. In any event, when we got into the car I told my spouse that in a million years I would never ever let such a person attend to her or would I suggest this physician to anyone. Any physician to ever state that they aren’t interested in learning something new immediately establishes your point about some of these “bad” physicians. Worse yet in my thinking this fellow was a Psychiatrist and couldn’t even think of a more diplomatic and plausible reason and response to not have interest. I guess my initial questioning caught him off guard.

        This anecdote leads me to also respond to some of the preceding commentary. I do not believe any patient or physician for that matter can ever be “fully informed”. I think it is incumbent upon the patient and/or his/her support people to be reasonably informed while the physician makes best efforts to be reasonably up-to-date in his/her specialty. I have always endorsed patient education and with the advent of the Internet the availability of information relating to medications, practices, treatments and articles such as yours etc., etc. are more readily at hand. Patients practicing “defensive medicine” in my opinion is counterproductive, negativism and wasteful of one’s time and efforts. Reading up on potential benefits of all treatments including drugs as well as potential serious side-effects and collaborating with one’s caring, trusted, knowledgeable and licensed health care practitioner should prepare as well as overcome many issues for the patient. Add to the fact there are far more Internet sites that lambast each and every medication and treatment regimen in addition to some calling for the banning of their use (“defensive medicine”) that if these folks had their druthers there would be no treatment options and we’d be back to medieval practices.

        I cannot speak for others but I am almost always reasonably informed before we undertook each and every treatment option along with being knowledgeable of potential side-effects. Being so equipped, vigilant and observant of my spouse we were able to avoid many of the pitfalls and side-effects I continue to read about from others. I learned many decades ago there were neither assurances nor guarantees of efficacy from any treatment undertakings nor did any of my spouse’s physicians utter words to that affect. In fact I coined a phrase those many years ago; “The Trial and Error Approach to Wellness” which still appears evident to this day.

        Once again, thank you for your response. There is a need for doctors such as you, doc Steve and others who advocate on patients behalf while exhibiting compassion and understanding of patient needs. Therefore and in my opinion there will be continuing need for folks like you in your profession and for the patient to help in charting one’s own course.

        Warmly,
        Herb
        vnsdepression@gmail.com
        http://www.vnstherapy-herb.blogspot.com

  12. Anonymouus says:

    Dear Mara, In response to your much earlier post, I would like to say, my sister has 2 doctorates, taught at Harvard, Yale, Juilliard, is a MacArthur fellow (music composition) and is completely dsyslexic and I have my own issues. Her real handicap was the good ole boy univ. stuff and she had the 7am classes to teach, while the much less talented had the more comfy schedule. She has had the last laugh with her tremendous success and recognition. My mother, knew, for me, as a sort of selective mute (not that I could not speak), and my sister, with everything sort of backwards found a place for both of us to thrive. She also did everything for my brothers, who were not too sharp either. Everyone has their strengths and weaknesses. Dyslexia is so real – she teaches composition, composes, counterpoint and just sees things a little different.

    My computer is acting strange and this is not my forte, so if this comes on screen with idiocy, it is because, yes, I am an idiot, but not dyslexic. My mother would brush our hair and count and she could teach a dog to read! I rarely speak, yet can speak at least 5 languages (speaking was not part of my career). There was no test for dyslexia in the 70′s, but her innate sensibilities to help all of my nuts, but loving family left us as contributing members (including our personal work and funding of charities) of society. I would consider my sister a brilliant, American, and she has been recognized in her realm often, and continues to thrive! Thanks for mentioning dyslexia, as it seems to be forgotten or thought of as an “end of story” disability.

  13. [...] but many critics are skeptical.  Likewise, a putative new blood test for depression raises many questions.)  At best, “chemical imbalance” is shorthand for a presumed brain abnormality that no [...]

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