Thursday, February 2, 2012

"Blood test accurately distinguishes depressed patients from healthy controls"

Update: Some criticism below.
The initial assessment of a blood test to help diagnose major depressive disorder indicates it may become a useful clinical tool. In a paper published in the journal Molecular Psychiatry, a team including Massachusetts General Hospital (MGH) researchers reports that a test analyzing levels of nine biomarkers accurately distinguished patients diagnosed with depression from control participants without significant false-positive results.

“Traditionally, diagnosis of major depression and other mental disorders has been made based on patients’ reported symptoms, but the accuracy of that process varies a great deal, often depending on the experience and resources of the clinician conducting the assessment,” says George Papakostas, MD, of the MGH Department of Psychiatry, lead and corresponding author of the report. “Adding an objective biological test could improve diagnostic accuracy and may also help us track individual patients’ response to treatment.”

(via ProHealth)
Molecular Psychiatry? While I think this is genuinely credible scientific inquest of the biomedical variety, this somehow sounds like a joke to me: What do you get when you cross a profession that thinks childhood traumata can explain everything (if I may exaggerate a bit), with a profession that sees the world on a molecular level? People working on opposite ends, ignoring the "middle" and bound to be oblivious of the environmental factors that can cause disease. They should maybe throw in a genetic epidemiologist for good measure.

Human bodies are hierarchically organized, as with all living beings a reflection of their evolutionary history. The biochemical level, the genetic level, the cellular level (with its sub-divisions!), the level of the organs, plus how they evolved to "solve" problems in the context of the ever-changing environment. Unfortunately I can't find Rolf Löther's introduction into biology now to give a good quote from him here. He was using a quote along the lines that if you focus on one single hierarchic element (say, the molecular level), you will learn nothing if you not take the entire living being with its many hierarchical elements in account. And an living being makes only sense in its (evolutionary) environment, just like a boats makes only sense in water or a cars makes only sense in the context of some kind of way they selected for. And molecular biology seems like the attempt to find out what is wrong with the suspension of a four door sedan (is it the rate of the suspension? The damping?), while one is driving with 80 mph on a dirt track, instead of a paved road.

Still, I think they are on the right track (on a molecular level, harhar). Maybe I do them injustice, but alas, I doubt they will find out how environmental factors, like say our (neolithic, western) nutrition, can play into depression.

Without further prose from me, here is the abstract:
Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study

G I Papakostas1, R C Shelton2, G Kinrys3, M E Henry4, B R Bakow1, S H Lipkin1, B Pi5, L Thurmond5 and J A Bilello5

1 Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
2 Vanderbilt University, Nashville, TN, USA
3 Cambridge Health Alliance and Harvard Medical School, Cambridge, MA, USA
4 Saint Elizabeth's Medical Center, Brighton, MA, USA
5 Ridge Diagnostics, Research Triangle Park, NC, USA
Correspondence: Dr GI Papakostas, Massachusetts General Hospital, Harvard Medical School, One Bowdoin Square, 6th Floor, Boston, MA 02114, USA.

Received 21 April 2011; Revised 14 July 2011; Accepted 7 November 2011; Published online 13 December 2011.

Despite decades of intensive research, the development of a diagnostic test for major depressive disorder (MDD) had proven to be a formidable and elusive task, with all individual marker-based approaches yielding insufficient sensitivity and specificity for clinical use.

In the present work, we examined the diagnostic performance of a multi-assay, serum-based test in two independent samples of patients with MDD.

Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis factor alpha receptor type II) in peripheral blood were measured in two samples of MDD patients, and one of the non-depressed control subjects.

Biomarkers measured were agreed upon a priori, and were selected on the basis of previous exploratory analyses in separate patient/control samples.

Individual assay values were combined mathematically to yield an MDDScore.

A ‘positive’ test, (consistent with the presence of MDD) was defined as an MDDScore of 50 or greater.

For the Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects. In this sample, the test demonstrated a sensitivity and specificity of 91.7% and 81.3%, respectively, in differentiating between the two groups.

The Replication Study involved 34 MDD subjects, and yielded nearly identical sensitivity and specificity (91.1% and 81%, respectively).

The results of the present study suggest that this test can differentiate MDD subjects from non-depressed controls with adequate sensitivity and specificity.

Further research is needed to confirm the performance of the test across various age and ethnic groups, and in different clinical settings.
So these were the markers they used:
  • Alpha1 antitrypsin
  • Apolipoprotein CIII
  • Brain-derived neurotrophic factor
  • Cortisol
  • Epidermal growth factor
  • Myeloperoxidase
  • Prolactin
  • Resistin
  • Soluble tumor necrosis factor alpha receptor type II 

Although there were two depressed patient groups (n=36 and 34), there was only one set of controls (n=43); both patient samples were compared to it. This means the second, "replication", test was not fully independent of the first one. If the first finding was a fluke caused by the control group having weird results by chance, for instance, then the second study would just repeat the fluke.

The patients were significantly older, and with a higher BMI, than the controls. They did control for these variables, which is good, but this raises the question of whether these folks differed in other ways, that they didn't measure, and hence couldn't control for.

In both samples, the patients had a very significantly higher MDDScore than the controls (p less than 0.0001, both times). But in both cases, the difference in levels of EGF (epidermal growth factor) was almost as strong: p=0.0003 and p less than 0.0001, respectively. Other metabolites weren't far behind. Testing for EGF would almost certainly be cheaper than getting an MDDScore.

Finally, all these data demonstrate is that the test can distinguish between people with MDD and entirely healthy people. But how often are doctors going to need to do that? More likely, they'll want to distinguish depression from other things that are often confused with it, such as: bipolar disorder, anxiety disorders, chronic fatigue syndrome, bereavement, "stress", and all manner of physical illnesses e.g. thyroid problems. …

1 comment:

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