
First Blood Test to Diagnose Depression in Adults? - nkurz
http://www.northwestern.edu/newscenter/stories/2014/09/first-blood-test-to-diagnose-depression-in-adults.html
======
gwern
Coyne's "How to critique claims of a “blood test for depression”"
[http://blogs.plos.org/mindthebrain/2014/09/25/critique-
claim...](http://blogs.plos.org/mindthebrain/2014/09/25/critique-claims-blood-
test-depression/) ; summary:

1\. priors for the phenomenon imply many small correlates, and past results
have failed to replicate

2\. low statistical power for claimed results, from both planned & post hoc
perspective

3\. small sample biases: can't estimate accurately (without relatively exotic
techniques) when p>n

4\. measurement error in diagnosing depression: investigators chose a self-
report of lower reliability compared to the available alternative data from a
more reliable interview that they had,

5\. substantial & likely biased attrition of subjects

6\. correlational result is confounded by antidepressant usage, smoking, etc
(many things correlate with being depressed, so any blood test may be picking
out those instead) and by the small sample size, results may not generalize

7\. failing multiple-comparison correction of final results

~~~
nkurz
Having posted this link, I feel bad for calling attention to a weak study when
I'd only read the press release. Yet I'm glad that doing so resulted in
someone (Gwern) providing a link to this excellent analytical rebuttal that I
probably wouldn't have encountered otherwise.

~~~
icelancer
Being rebutted by gwern on a topic of blood chemistry and/or mind-altering
drugs isn't anything to be ashamed of. If you were unaware, this is but one of
many outstanding "articles" available on his site at no charge:

[http://www.gwern.net/Nootropics](http://www.gwern.net/Nootropics)

------
jrapdx3
The article presents a rather stark claim that nine RNA "markers" in a blood
sample "were able to diagnose depression". Unfortunately, the article is shy
on the details necessary to evaluate the merit of the claim.

Since depression is a quite heterogeneous condition, it's unlikely that any
particular test will give unambiguous results in every subset of depressed
patients. There's bound to be "fuzziness" in a substantial portion of cases.

ATM I don't have time to discuss the subject in any depth, but I do think the
problem is going to be the media reporting this as an absolute fact, not only
terribly misleading to the public, but even worse, undermining the
researchers' good efforts.

~~~
Florin_Andrei
> _I do think the problem is going to be the media reporting this as an
> absolute fact, not only terribly misleading to the public, but even worse,
> undermining the researchers ' good efforts._

This tends to apply to a very large fraction of all science-related news.

~~~
roywiggins
This isn't even news, it's a press release.

------
rmxt
Free link to the published paper, "Blood transcriptomic biomarkers in adult
primary care patients with major depressive disorder undergoing cognitive
behavioral therapy":

[http://www.nature.com/tp/journal/v4/n9/full/tp201466a.html](http://www.nature.com/tp/journal/v4/n9/full/tp201466a.html)

------
stared
This is "too good to be true". A critique is here:
[http://jcoynester.wordpress.com/2014/09/23/talking-back-
to-t...](http://jcoynester.wordpress.com/2014/09/23/talking-back-to-the-
authors-of-the-northwestern-blood-test-for-depression-study/)

In short - an unexpected result, based on a very small sample and trying to
give even further implications (on effectiveness of cognitive behavioral
therapy).

------
mr_tyzic
Naively, nine markers sounds like a lot. How high is the risk of curve-
fitting?

~~~
michaelhoffman
Very high. There are standard procedures for avoiding overfitting in
developing "omic" biomarker tests, which, of course, the authors did not
follow.

------
nashashmi
Apart from possibility, one thing bothers me here is that how quickly (and
arrogantly) they will match viability of cognitive therapy to RNA markers.
Cognitive therapy works and does not work for so many reasons, and none of
those reasons have anything even remotely to do with RNA.

I am saddened and angry that in the end, the researchers will show and justify
the experiment using results based on statistics. What medicines and therapies
work and do not work will be left to chance, random trial and error, and
complicated numbers. The statistics will fail to acknowledge and show the
situations and mental states of the patients at that time in which such and
such therapy was possible or not possible.

------
zoba
I'm curious what happens if the markers are removed. For example, if one of
the markers is that you've got too much X in your system, and you take a drug
that binds to X and then is flushed out of your system - do you stay
depressed?

~~~
gwern
Almost certainly not. Biological systems are deeply complicated intertangled
nests of cause and effect; when you measure a correlation between two
variables (such as being depressed and lower/higher levels of RNA X), it's not
going to be a direct causal link, you're much more likely to have picked up on
a distant indirect relationship. (I have an essay on this topic which you
might have seen on HN before:
[http://gwern.net/Causality](http://gwern.net/Causality) )

In this case, if you skim the depression literature, you'll find depression
linked with all sorts of things - too much sleep, too little sleep, weight
changes, poorer cognitive performance, high inflammation levels, bad eating
habits, stimulants, etc etc. Any of these could be a good predictor of
depression but changing them will not help or may harm. (If a depressed person
finds modafinil helps them get through the day, a naive investigator may find
modafinil correlates with depression - and take it away. Not going to help.)

------
virtue3
As someone that's suffered from depression for a very long time (and totally
messed up my adolescence) this is a very good thing.

It is _very_ difficult to accurate diagnose these disorders and then half the
time people don't believe you anyway. It's a very difficult disorder to convey
to other people because it just doesn't resonate unless you've gone through it
or have been clinically diagnosed (there's a huge huge difference between
being down for a few weeks and having no joy in anything for years seemingly
out of no where).

~~~
lutusp
> It is _very_ difficult to accurate diagnose these disorders and then half
> the time people don't believe you anyway.

Fair enough. Which do you think is worse -- a false positive or a false
negative? I ask because this diagnostic category has plenty of both.

I would want to be very sure about a depression diagnosis before assigning it,
especially to young person with little life experience. These questionable
diagnoses can change the direction of a person's life, possibly cause him to
think of himself as permanently handicapped, brain-damaged, after a spell of
the blues followed by a superficial diagnosis from a "professional".

Because of how little we know about depression, most diagnoses are in a gray
area. It's not like there's a blood test -- and if you've read the posts in
this thread, you know by now that there isn't a blood test, there's only a
press release.

~~~
virtue3
I'm not really gonna go to deep into it but my personal feelings are a false
positive would be infinitely worse.

Those drugs they give you do shit to you. I've been permanently altered from
taking them when I was in my adolescence (I can remember feeling
_significantly_ different pre and post drugs, and I've been off for many man
years). There's a reason I'm not very keen on the "keep trying them till
something sticks" approach that we take with this crap. Especially with
developing individuals.

------
jjallen
Isn't this the kind of thing that diagnoses itself, in that someone super
unhappy will seek the test out? Do they need a blood test to determine if
they're seriously depressed or not?

Why would someone that isn't depressed ever get this test?

~~~
girvo
If it becomes powerful enough, you could be checked for whether or not you're
predisposed to depression above and beyond what we currently have (family
history, mostly), allowing you to take the steps needed and learn the skills
necessary to cope with it.

CBT allowed me to beat my depression, but learning it while depressed was nigh
on impossible. If I'd known that I suffered from depression or _could in the
future_ , I might have had the chance to learn it prior to my first episode,
setting me up to be able to live with it far easier and with far less drama
than I ended up going through.

------
mvgoogler
This seems like a 21st century version of phrenology more than something that
"brings mental health diagnosis into the 21st century".

Just replace measuring skulls with measuring "RNA molecules".

------
pc2g4d
N=32

There you go

~~~
erehweb
We really need to say more than just "N = 32". If you're tossing coins, and
the treatment group gets 16 heads, that's a significant result. Not saying
that's the case for this particular study, but general point is that N = 32 is
not enough to dismiss a study out of hand.

~~~
pc2g4d
You'd have a stronger point if this study was an experimental intervention
with binary outcomes. However, what this study was actually doing was fishing
for correlations between various blood factors and depression. Thus the small
sample size greatly increases the chance that some factor will "just happen"
to be more likely in the 32 depressed patients than in the 32 non-depressed
ones.

So I stand by "N = 32" as a valid critique of the study.

------
vaadu
How would the results distinguish between real depression and your down
because your cat just died?

------
pessimizer
This doesn't look like a yes/no test; it seems more astrological.

------
dang
NPR covered this the other day:

[http://www.npr.org/2014/09/28/352290040/finding-
depression-i...](http://www.npr.org/2014/09/28/352290040/finding-depression-
in-the-blood-stream)

I thought about posting it to HN, but it says nothing about the actual test,
other than that it might not work.

------
lutusp
Quote: " ... a breakthrough approach that provides the first objective,
scientific diagnosis for depression."

Wait ... an "objective, scientific diagnosis" that doesn't identify the cause
of the ailment? If I visited a doctor and she said, "You're running a fever,
and your blood has cooties," I wouldn't think of that as the height of medical
expertise, and it's certainly not science.

In science, we establish causes and then measure effects. This test measures
effects. No one knows what causes depression, therapy is indistinguishable
from the placebo effect, and existing medications have a terrible reputation.

This claim is way ahead of the evidence, evidence that in principle would
identify the source of depression, offer an explanation to replace these many
descriptions, and (at long last) craft a meaningful treatment.

EDIT: Okay, before you people downvote my completely accurate post, read this:

[http://en.wikipedia.org/wiki/Scientific_theory](http://en.wikipedia.org/wiki/Scientific_theory)

Quote: "Scientific theories are testable and make _falsifiable predictions_.
They describe the _causal elements_ responsible for a particular natural
phenomenon, and are used to _explain and predict_ aspects of the physical
universe or specific areas of inquiry (e.g. electricity, chemistry,
astronomy)."

Feel free to drop by the source and downvote it too, while you're banging your
mouse in ignorance.

~~~
dragonwriter
> In science, we establish causes and then measure effects.

No, in science, we observe and measure phenomena, then form hypotheses about
relations between them, then attempt to falsify those hypotheses, and then use
the hypothesized relations which we have not yet falsified as a basis for
_inferring_ likely causes from observed effects and inferring likely effects
from observed causes and inferring likely co-occurrences that are the results
of common (and potentially unknown) causes from the other co-occurring
phenomena.

"Establish causes and then measure effects" is not only wrong, its non-sense.
To even be able to establish the likelihood of a causal relation you must
first measure effects _and_ the phenomenon hypothesized as the cause.

~~~
lutusp
> "Establish causes and then measure effects" is not only wrong, its non-
> sense.

All right, so you don't understand science. It's not fatal, and you're hardly
alone.

From Aristotle, through Francis Bacon, to the present, the centerpiece of
science has been the establishment of causes, _explanations_ , not merely
observations and descriptions as you're suggesting.

Observations often lead to the shaping of a theory, then confirmation of that
theory -- that _explanation_ \-- through the prediction of phenomena not yet
observed, and observations that confirm the predictions (or that falsify the
theory).

[http://en.wikipedia.org/wiki/Scientific_theory](http://en.wikipedia.org/wiki/Scientific_theory)

Quote: "Scientific theories are testable and _make falsifiable predictions_.
They describe the _causal elements_ responsible for a particular natural
phenomenon, and are used to _explain and predict_ aspects of the physical
universe or specific areas of inquiry (e.g. electricity, chemistry,
astronomy)."

I could provide hundreds of quotes similar to that above, but I can't repair
your education in a short post. You must accept responsibility for those
things you don't understand, but that you feel comfortable reciting to other
people in a public show of narcissism.

