Biomarkers

[nexus73]

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New Blood Test Developed for Depression and Bipolar Disorder

The RNA-based biomarkers test may ultimately lead to tailored medication choices for patients with depression—an area of significant need where most patients routinely cycle through a variety of treatments to find one with some efficacy.

www.clinicalomics.com

Is this really coming? What are your thoughts?

 

[NickNaylor]

The title of the article misses the point of the findings, I think. Doesn't seem to be clinically applicable at this point... these kinds of findings are not novel and have been described for psychiatric disorders for more than a decade, but you don't see anyone ordering specific biomarkers for psychiatric diseases.

I think it's interesting research that may have some fruit to bare in the future, but I don't expect any big changes in the near-term.

 

[WisNeuro]

This stuff comes in waves, in both the psychiatry and neurology worlds. Maybe someday they will be useful clinically, but today is not that day. I still remember the hype of measuring beta amyloid and people thinking it was the diagnostic holy grail. And then they discovered that everyone over a certain age had it, and that amyloid burden was actually not that great of a predictor of cognitive impairment or i/ADL impairment.

Biomarker and genetic studies in psych have some of the poorest replication figures in medical research. I don't know much at all about RNA based biomarkers, so who knows, maybe this will be the breakthrough? But, even if there is something there, it will need a lot more work and development to get to clinical primetime.

 

[tr]

I think the main potential clinical utility from that paper relates to their report that expression of circadian clock-related genes can help you suss out bipolar depression from unipolar. That is potentially helpful, as the distinction of unipolar from bipolar is critical for making appropriate treatment decisions but also very tricky to do with a clinical interview. I think if they were to package just the circadian biomarkers and promote them as a guide to differentiating unipolar from bipolar that might be something that could have a definite clinical application.

I'm not sure that predicting depressive severity/future hospitalization for unipolar is so useful as it isn't necessarily going to change your management so much in the moment that you're in.

Other than that, I think the utility of this study is more about understanding biological pathways related to mood disorders vs anything with direct clinical utility right now.

Generally, a big problem with clinical application of biomarkers in psychiatry is that, like the clinical symptoms themselves, the biomarkers invariably exist along a spectrum. Biomarkers that conclusively indicate absence/presence of disease are rare in psychiatry. Anti-NMDAR antibodies are the only one I can think of offhand. Even thyroid is subject to ultimately arbitrary cutoffs.

What they've done here is take a whole bunch of spectrum-y biomarkers and combine them so that the predictive value of the overall set is better than that of any individual biomarker. That improves prediction overall but still doesn't give you a clear yes/no, go/no-go like you would want in a test if you were going to order it and expect it to be useful clinically.

 

[Fan_of_Meehl]

1) what does the sensitivity/specificity look like in relation to structured interview diagnosed MDD/ bipolar disorder (current gold standard, at least for research)?
2) if depression/BP is reconceptualized as a disturbance in underlying specific pathophysiological disturbances that can be reliably measured and which reliably/validly distinguish between 'normal' and mood d/o diagnosed samples, then wouldn't this move the disorder out of the province of psychiatry and more into the province of the appropriate corresponding medical specialty?
3) still have to explore the issue of causation, behavioral treatments can have physiological effects
4) they make a good point re: the need to cross-validate/ confirm their findings on fresh samples...'shrinkage' is real

 

[Merovinge]

Generally, a big problem with clinical application of biomarkers in psychiatry is that, like the clinical symptoms themselves, the biomarkers invariably exist along a spectrum. Biomarkers that conclusively indicate absence/presence of disease are rare in psychiatry. Anti-NMDAR antibodies are the only one I can think of offhand. Even thyroid is subject to ultimately arbitrary cutoffs.

While they exist along a spectrum, I think we would all agree at some point along the spectrum they do very heavily indicate a casual reason for disease. There is a clear different between TSH undetectable and 0.6 for considering thyrotoxicosis (bad example given you would have T3/T4 but still), and I think most people would agree that abnormalities in electrolytes or WBC are increasingly likely to be the cause of delirium the further away from normal they become (e.g. Na of 130 gets admitted to psych inpatient but a Na of 115 would be entirely different, WBC of 12 and 40 suggest different likelihood of infection causing AMS). BP is clearly on a spectrum and varying values clearly indicate different pathology/treatment. Just a long winded way to say that the value in the test can still exist even if only the far tails of the distribution heavily imply or change management/diagnosis.