a buddy system…

Posted on Sunday 21 September 2014

"So what we wanted to do is to find a diagnostic test that can be done in any clinical laboratory whereby a patient can go to the doctor and the doctor can send blood to the clinical laboratory that can help the physician to decide if the patient is clinically depressed or not. It will help them to live better lives, but it also would help to eliminate the stigma, because if there is an objective measure, a blood test, that can tell whether you are depressed or not, that it’s not likely that anyone can tell you ‘Oh, just get over it.’ In addition to eliminating the stigma, and of course to help the physician make a correct diagnosis, we are also helping society altogether, as depression is going to be the number one burden in the world by 2030."

When I looked at Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy on Friday [see don’t ask, don’t tell…], I read the write up in TIME Magazine, and linked the one in the  Chicago Tribune, but I hadn’t gone to the site. It was a videotaped interview with Eva Redei, PhD, the senior author. I transcribed it [above] thinking I wanted to write about it. It’s the kind of exaggerating I just hate. But once I heard it, I went back and looked at the article itself. In don’t ask, don’t tell… , I had been sarcastic: my blog title, their small sample size, the pay for publication online journal, I made fun of needing a test to know if you’re depressed [or better]. Maybe I looked back at it because I felt guilty about being so sort of nasty. I know I planned to pan that interview, which I thought was a sham, particularly the  plague-of-depression ending. So I read it through again, looked at the tables, and instead of softening, I went from sarcastic to bombastic.

Your don’t need to hear another rant, so I thought I’d just stick to the sleight of hand that set me off. These two tables below are from the article with a few additions of my own – the red highlighting, and the columns and headers in shades of salmon: The upper table has the BASELINE data for control and MDD subjects and the lower one is both groups at 18 weeks:


I couldn’t figure out why there were two control groups, and why they were different. They were just an age/sex/race matched group used to assay the distribution of the various RNAs they looked at. So I did some Student T-Tests like they prescribed but got very different results. Then I reread the methods. They did paired T-Tests! What that means is that every MDD case had a unique age/sex/race matched control subject:
    Paired t-tests are a form of blocking, and have greater power than unpaired tests when the paired units are similar with respect to "noise factors" that are independent of membership in the two groups being compared…

    A paired samples t-test based on a "matched-pairs sample" results from an unpaired sample that is subsequently used to form a paired sample, by using additional variables that were measured along with the variable of interest. The matching is carried out by identifying pairs of values consisting of one observation from each of the two samples, where the pair is similar in terms of other measured variables. This approach is sometimes used in observational studies to reduce or eliminate the effects of confounding factors.

That greatly increased their power to find a significant difference, but it plays havoc with Dr. Redei’s comment above, "…the doctor can send blood to the clinical laboratory that can help the physician to decide if the patient is clinically depressed or not." This is more like it:
    If you go to the doctor for this test, be sure that you take an age/sex/race matched friend who’s not depressed to act as your matched control – it’s sort of a "buddy system"
which is, of course, ridiculous [actually, even that wouldn’t be enough]. They had also calculated Cohen’s D [see about my connectomes]. So I redid those Effect Sizes too and they were also very different! I couldn’t figure out why from the methods, but I suspected it was some matched pair method similar to the T-Tests. Who knows? I couldn’t check their figures as the individual values weren’t included. Just more smoke and mirrors . this time it’s not from PHARMA – but likely some plan to market this test.

If someone actually really found a blood test that accurately correlated with depression, including being able to discriminate active depression from the trait of being a depressive, the American Journal of Psychiatry, the British Journal of Psychiatry, and JAMA Psychiatry would be fighting over the chance to publish it. It wouldn’t be tucked away in a pay-for-play online journal. It would already be in the PsychiatricNews and the author would be being bombarded with speaking engagement requests. That’s certainly not what we have here…

…but if you read those media reports and watch the video, this is the very giant leap forward she’s talking about…
    September 21, 2014 | 11:52 PM


    “How are you feeling lately?

    Are you getting enough sleep?

    Are you sleeping well?

    Do you have a good appetite?

    Are you having any noticeable problems with cognition and memory that concern you?

    Do you feel like you can reasonably handle most of the stress in your life?

    Do you feel strong and healthy?

    Do you feel like your outlook is pretty much appropriate for your situation?”

    Etc, is too subjective and makes the assumption that you may not want intervention nor are you asking for it.


    September 22, 2014 | 2:07 AM

    For a third control, I recommend bringing a dead salmon. Surely, its revelatory value is not limited to the medium of the MRI.

    September 22, 2014 | 5:47 AM

    Regarding blood tests for depression and stigma, if a “mainstream” physician sees in your chart that you are taking Prozac for depression, in many cases (not all), everything is going to be seen through that lens. He/she is not going to ask how you are diagnosed.

    In other words, if you have symptoms that scream sleep apnea as that is typically misdiagnosed as depression, chances are that blood test you had diagnosing you as having depression is not going to reduce stigma at all. And to claim otherwise is totally misrepresenting the situation.

    Steve Lucas
    September 22, 2014 | 7:46 AM

    “as depression is going to be the number one burden in the world by 2030.”

    I have the bad habit of looking at everything through a business lens. The above quote is an appeal to authority, a straw man argument, as well as setting up anyone who argues with a personal attack.

    Many years ago we learned linear regression. This was the brave new world of mathematics that was going to revolutionize business. The instructor would throw some numbers up on a graph and we, using our calibrated eye ball would come up with an estimate and then do the math to get a more precise answer.

    We would then match that answer against other factors such as market size, available resources, and reality.

    “as depression is going” becomes our statement of fact or appeal to authority.

    “the number one burden” becomes our straw man argument because who knows.

    The original tables become our personal attack as only someone with the appropriated math skills will counter the attack and then you get into an endless debate about the numbers.

    Pharma has been for many decades solely a sales organization, and by extension such things as the device industry and other services. They do occasionally produce a viable product in order to maintain their legitimacy in the public eye.

    This “blood test” is nothing more than another marketing product all tied up in the usual pharma smoke and mirrors and does not pass the old reality test.

    A few years after graduate school we bought our first computer, and I bought for $5.00, a stat pak on a hard floppy. Yes I am that old. That $5.00 would do all of the math I had spent hours doing in college in seconds, but still did nothing for the reality test.

    This does not pass the reality test.

    Steve Lucas

    James O'Brien, M.D.
    September 22, 2014 | 9:56 AM

    The stigma accusation is also a straw man the APA can’t get enough of and an endless rehash of a 1978ish Paul Fink lecture that was relevant at the time but not now. The stigma is not against people with depression, it’s against cargo cult science that doesn’t pass the smell test. No, depression isn’t “just like” pneumonia and any honest doctor with an elementary understanding of taxonomy will confirm that. We may want all mental illnesses (which are now too broadly defined to make this practical) to be covered like medical conditions, but too many of us feel like we have to lie to make that happen. Right now the case can be made on ethical but not scientific grounds.

    And to be honest I don’t want to hear about “scientific” blood tests from the same crowd that is A-OK with depression screening by GPs using the PHQ-9. So much for ethics and rigor.

    There actually is a better test for detecting depressive endophenotypes..the 2 scale of a valid MMPI-2. Somehow we don’t hear about that one anymore because it is “1940ish” and not high tech.

    Let’s not give the more “prestigious” journals too much credit. They’ve been publishing plenty of dead-end and garbage studies for decades.

    September 22, 2014 | 10:36 AM

    Dr. O’Brien,

    Actually, in alot of mainstream medicine, there is stigma against anyone with a psych med history which would include depression. Someone mentioned to me that a serious health issue was missed because there was a psych diagnosis in the person’s chart and everything was seen through that lens.

    Again, my point is it doesn’t matter if this is done through a blood test or an MMPI-2. Many people in psychiatry seem to want to overlook this issue and pretend it doesn’t exist.

    James O'Brien, M.D.
    September 22, 2014 | 10:58 AM

    “Many people in psychiatry seem to want to overlook this issue and pretend it doesn’t exist.”

    Really? What APA President hasn’t repeatedly banged the podium on this issue over and over again especially when asking for funding? And psychiatrists in positions of power love to bring it up when the science is challenged.

    The issue isn’t ignored at all…it’s brought up repeatedly and inappropriately. As if nothing has changed since the 1950s.

    Missing a diagnosis in depression isn’t necessarily an indication of stigma…in general diagnosis is harder if there are comorbidities.

    September 22, 2014 | 1:01 PM

    Dr. O’Brien,

    I didn’t say that a diagnosis of depression was missed. I said that if someone has a psych med diagnosis, any other serious medical issue may be overlooked because everything is seen through the mental health health issue. That is what I meant when I said that I feel that many people in psychiatry overlook this issue and don’t understand how their patients are stigmatized when they see a regular doctor in response to a regular medical complaint that may get erroneously blown off as psychiatric.

    September 22, 2014 | 1:11 PM

    James, AA,

    I think both things are true. There is a harmful stigma AND the stigma argument is mis-used for other things. Jeffrey Lieberman, in his president days, blew off all of psychiatry’s critics as basically succumbing to stigmatizing. In a free clinic, I can get away with not recording psych diagnoses because they can lead to the patient being discounted. I doubt one can do that elsewhere as a Dx is required for insurance etc. Stigma guaranteed…

    James O'Brien, M.D.
    September 22, 2014 | 1:49 PM

    I agree with you Mickey on all points, but it seems like APA Presidents are still pretending it’s 1954.

    Let’s acknowledge that media influences like the Sopranos and Loveline have made psychiatric and psychological intervention more acceptable, even chic. Especially for men.

    A hypothetical middle aged depressed male sees a psychotherapist and goes on an SSRI/SNRI or alternatively, drowns his sorrows in double Manhattans, chain smoking and quasiviolent acting out against his wife and kids because only crazy people see shrinks.

    In 1954, the former would have been stigmatized by friends and community, in 2014, there is no doubt in my mind that latter would be stigmatized while the former would be applauded.

    You have to acknowledge when society has changed for the better. And on this issue it has.

    September 22, 2014 | 2:54 PM

    I think that the main problem with this approach to mental health is that it divides those with depressive symptoms into those who have “real” depression and those who don’t. What would the authors have us do with those who suffer depressive symptoms but who are judged to not be depressed based on a blood test? Sure we can work them up for other illnesses that can masquerade as depression, but even so, there will be false negatives. Also, what happens to those who are false positives? Should they be treated as depressed even if their problem is not major depression?

    I don’t think this test (even if it worked) would solve anything clinically, though it would be interesting from a basic science viewpoint.

    September 22, 2014 | 3:19 PM

    In reference to Steve’s business model, I see the inventories and this imaginary blood test as “hooks”. I think patients should have the right to refuse tests for conditions they’re not asking to be treated and the right to turn down interventions that they don’t see to be relevant to them. I think there may be a stigma in some quarters with people who won’t bite.

    September 22, 2014 | 3:26 PM

    From what I’ve seen, nowhere is the stigma of mental illness greater than in a doctor’s mind. As AA says, a patient with such a history is considered an unreliable witness to their own bodily functions and symptoms and thus discounted.

    The rest of society doesn’t seem to care that much, given that so many people are taking psychiatric drugs as it is, a psychiatric diagnosis being assumed in those cases.

    As for the assumption that “depressives” (definition, please) are different biologically from everyone else, that’s based in the very offensive belief that unlike truly healthy people, because of a fundamental flaw some people react to trauma by becoming “depressed.” This makes me uneasy for many reasons, not the least the whiff of superstition around it.

    In so many ways, we are still primitive post-primates looking for a big juju potion for the purification of evil spirits.

    Steve Lucas
    September 22, 2014 | 5:01 PM


    We have the right to turn down test now, in theory. I always decline a PSA test in part as a test to see if the physician will follow instructions and due to some childhood interactions with urologist I feel comfortable with watching for prostate symptoms myself.

    The problem is doctors include this test even after being told I do not want this included in my blood work. The last blood work I had done ended up producing three pages of single spaced results and the comment when I returned to the doctor’s office was I needed immediate medication. All of the acceptable ranges were printed and my results were dead center or better.

    In the comment section of another blog post a mother related how she could not trust the doctor’s PA alone in a room with her son as she found this person about to inject him with the HPV vaccine without her permission. The tone of the post was frantic as she felt the PA was not trustworthy.

    You are correct these are “hooks” followed by “the insurance will pay for it” and “you can never be too sure.”

    We certainly do not need any person placed on any medication with out cause. One interesting topic that comes up here and on other blogs is polypharmacy. Usually by older doctors, who like Mickey, are trying to reduce the medication load of people who are left confused and in financial distress by an ever increasing medication regime.

    Steve Lucas

    September 22, 2014 | 7:19 PM

    Well, Steve, I’ve fallen victim to polypharmacy and had to pull my way out it twice–with psychiatrists and with three doctors for MS and general care like “preventive care”. It’s appears to be the rule and takes quite a lot of effort, research and self-examination to sort through. I’m somewhat privileged to have time to do that. Some of my research led me here, and I appreciate the influences and information greatly.

    When given a depression inventory, I write on it, “I do not consider this a legitimate instrument, if you want to know how I’m doing, ask.” Since I get my care from the V.A. and most veterans are bigger than I am and equally intolerant of infantilizing behavior, it’s not a problem for me.

    September 22, 2014 | 9:43 PM

    What a great idea, wiley.

    September 22, 2014 | 10:00 PM


    We certainly do not need any person placed on any medication with out cause. One interesting topic that comes up here and on other blogs is polypharmacy.

    Thanks for mentioning that. One thing that happens a lot is some new medication gets added without stopping the last one. I often ask people to bring all their medications to appointments. It’s chilling at times the size of the sacks that show up. I think it’s important for them to leave with two sacks – current medications and stopped medications. I often write what they are for, or DISCONTINUED on the labels. Going through the meds one at a time is a useful exercise, particularly in a clinic where they might be seeing multiple clinicians, and they actually seem to appreciate the effort…

    September 23, 2014 | 8:35 PM

    Dr. Mickey, if we could only clone you….

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