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A blood test may help the diagnosis and treatment of depression (economist.com)
90 points by eciffo on May 4, 2021 | hide | past | favorite | 53 comments




A problem with modern psychology is the diagnostic criteria aren't very much based on underlying causes as on being able to reliably diagnose patients based on symptoms regardless of physician. This leads to people agreeing what your diagnosis is without a strong or particularly useful set of understanding of what caused it or a specific treatment to change those causes (which is why so many people are on SSRIs). Historically there just wasn't much to go on when it came to determining underlying causes but neuroscience is catching up with understanding much more about how brains actually work.

The point is "depression" or "PTSD" probably don't exist among many others. There are perhaps dozens or hundreds of unique conditions currently lumped together because they present in vaguely similar ways - the good news is that we are making progress towards much more arguably "real" understandings, the bad news is we're still quite far away from diagnosing mental conditions with the same specificity we can diagnose cancers or viruses.


> A problem with modern psychology is the diagnostic criteria aren't very much based on underlying causes as on being able to reliably diagnose patients based on symptoms regardless of physician.

That’s generally true of diagnosis when we don’t understand the mechanism, and since where we do understand the mechanism we treat that as a reason to move the thing-with-behavioral-symptoms out of psychology and into some other medical domain, so its essentially an irreducible problem with psychology.


A diagnostician which crosses all specialties would be really nice. I imagine this is an area where an easily replicated computing tool might be the best advancement in the field. Initial symptoms and the low hanging easy tests (as well as any others 'that may as well also be run' for any labs or test types indicated given a moderate extra effort) would drive a root cause diagnosis and recommendation for a specialist who can best treat any of the possibly multiple issues.


The reason doctors become specialized is that they can't learn multiple, and definitely not all, specialities to a good enough degree to be able to diagnose and treat patients across them. There's probably a better chance to have a diagnosis team that meets and handles this type of thing, but it would likely significantly increase the cost of medical care if every patient had to go through a team of specialists.

And as for computer aid in this area, it would be awesome, but I fear we are still far away from it, especially since diagnosis is an interactive, continuous process, and is not separate from treatment. The patient presents with some symptoms a history and a current course of treatment, you order some tests and may even prescribe some medication for a preliminary diagnosis, then you wait and adjust as new information comes along. I'm not sure current approaches in machine learning deal very well with this type of process.


I find it remarkable that conventional expert systems didn't succeed at that. It seems like a straightforward application. If you have symptoms X, Y, and Z, then it could be P, Q, or R, so run tests T1 and T2.

Obviously I'm not a doctor and can only assume that this is like somebody telling me "Debugging is easy, you just set a breakpoint..." But I'd be curious to know more about why this approach failed.


I think the problem is that the expert system's fact base would have to be essentially the world's most complex medical encyclopedia, except that encyclopedias are addressed to thinking humans, whereas this would have to have enough detail so that it can be "read" by an extremely simplistic algorithm. And not only that, but it would have to be in constant update as new medical knowledge is discovered, new medications (with new interactions) come out etc.

I also wonder how well the inference algorithms would actually perform with the scale of facts you would need to add.


For well understood you don't need complicated machine learning you just need a searchable dictionary of test outcomes and flow diagnosis flow charts, these things already exist.


What you describe is essentially a general practitioner. If you look at what they do (and how their training is organised), they essentially follow decision trees to either a clear diagnosis or "refer to specialist". The difficulty for using computers for this tasks is that several of the things going into the tree are based on observations of the patients behaviour, look, speech etc., which is difficult to categorise for a machine.


> A problem with modern psychology is the diagnostic criteria aren't very much based on underlying causes as on being able to reliably diagnose patients based on symptoms regardless of physician. This leads to people agreeing what your diagnosis is

That is true. The groupings persist because they are useful in facilitating communication regarding potential complications, prognosis, and patterns of response to treatments.

People seem intent on throwing away the above utility with a backhanded “but that’s not the Real Diagnosis.” It’s not, but within the limitations of our current understanding of neurology, it’s the best we have come up with so far (allowing for some limitations due to the pace of spread of innovations, politicking, etc.)


Clinician and researcher in mental health here. In my view, you're being too charitable.

> The groupings persist because they are useful in facilitating communication regarding potential complications, prognosis, and patterns of response to treatments.

These are reasons, but they're a distant second. Mainly, they persist because those groupings - diagnoses, in other words - have become necessary for billing. The DSM, for instance, is an economic document, not a scientific one. For most people, it sits on a shelf, gathering dust.

As for "the best we've come up with so far", you'd perhaps be interested to learn how often the decisions about these groupings are made because of politics and economics, and not by science [1].

[1] https://www.amazon.com/They-Youre-Crazy-Paula-Caplan/dp/0201...


Thank you for coming out with us! I tell my doctors all the time, I’m tired of being diagnosed, I want you to listen to how I feel. That has got to be so much further in helping me than any diagnosis has.


> The point is "depression" or "PTSD" probably don't exist among many others. There are perhaps dozens or hundreds of unique conditions currently lumped together because they present in vaguely similar ways - the good news is that we are making progress towards much more arguably "real" understandings, the bad news is we're still quite far away from diagnosing mental conditions with the same specificity we can diagnose cancers or viruses.

One sees this in a bizarre number of fields, that specialists act as though the classifications actually be as rigid and objective as in, say, physics, and that something objectively is or is not something, and then debate it.

I've actually read some debates between linguistics that are quite passionately debating whether something is an allophone of the same phoneme, or a different phoneme altogether, and I do not find such distinctions to be all that objective as the language they used suggests.


Name magic.

To know a thing's name is to have power over it.

From ancient mythos to modern specialists and especially philosophy, naming things gets a whole lot of focus. It does because it is terrifically useful! Naming, separating, making distinctions, this is an essential part of understanding.

However a whole lot of these kinds of debates don't acknowledge what kind of a debate they are actually happening. Is the subject of debate the limits of where a definition matches and were it doesn't? Is it whether the subject fits within already agreed limits? Is it really about an unspoken assumption that differs between the parties arguing? Many also don't address the quality of the definition. Is it a useful definition that represents defensible differences between "has this name" and "doesn't have this name" or is it an entirely arbitrary classification (say, look at the color spectrum and define areas which are red and which are orange; now zoom in on a boundary between the two, is there any defensible reason why the border should not be moved slightly to add one color to red? No, probably not)

> I've actually read some debates between linguistics that are quite passionately debating whether something is an allophone of the same phoneme

In this example are they really arguing about the something in question or are they arguing about the definition of "allophone" without realizing it. The followup question is "what is the reason why this edge case is relevant?" and "if this edge case isn't relevant, is the term 'allophone' even useful?"


> In this example are they really arguing about the something in question or are they arguing about the definition of "allophone" without realizing it. The followup question is "what is the reason why this edge case is relevant?" and "if this edge case isn't relevant, is the term 'allophone' even useful?"

I do not believe they are arguing about the definition either, nor do I believe that the classification has any use as whichever way it falls changes nothing.

Linguistics is a field plagued by classification for it's own sake, as many others are. Objects are classified but no conclusions can be drawn from the classification. — perhaps it is but simply a form of mental file organization.


In the majority of US States, psychologists cannot prescribe medications.

https://www.verywellmind.com/can-psychologists-prescribe-med...


These conversations tend to conflate psychology and psychiatry. Which isn't altogether unreasonable.


I would have used a more generic term to include both if I knew one. Psyche-related healthcare providers and the science behind them? Meh.


> Depression’s diagnosis has, though, a worryingly arbitrary quality to it, depending as it does on a doctor’s assessment of a patient’s mood against a checklist of symptoms which may be present in different combinations and are often, in any case, subjective. This has led to a search for reliable biochemical markers of the illness. Not only might these assist diagnosis, they may also improve assessments of prognosis and point towards the most effective treatment in a particular case. Now, a group of neuroscientists at Indiana University, in Indianapolis, led by Alexander Niculescu, think they have found a set of markers that can do all this.

Such markers have long existed and been found. This wording suggests that this is the first attempt.

The markers are always only correlative, and obviously it won't happen that, if a patient show the markers, but otherwise show no subjective, he'll be diagnosed with depression, or vice versā, denied such a diagnosis, if he show the symptoms, but not the markers.

> Together, these 13 RNA markers form the basis of a blood test that can not only diagnose depression,

“diagnose”? I doubt that it will replace subjective diagnosis for the aforementioned reason. — the subjective diagnosis will remain the final judgement for a time long to come.


There's a saying that "you don't treat test results". Tests always just inform a diagnosis and usually are not even performed if patient is not suffering any symptoms.


Agreed. Many psychiatric disorders are a function of personal experience and of collective experience of the person. Whilst I'd welcome more objective and quantitative assessment tools, it feels like blood tests won't ever tell you if a person is depressed. They might suggest a level of inflammation or endocrine stress, and that's a great help, but not equivalent.


> Many psychiatric disorders are a function of personal experience and of collective experience of the person

[Citation needed]

That seems like a bold claim relative to our current level of understanding.


Why do you think that?

If there is one thing that we do know it is that depression, say, is multifactorial and complex. In very few cases are the reasons only biological (but they do exist). See e.g.

https://en.m.wikipedia.org/wiki/Biopsychosocial_model

https://en.m.wikipedia.org/wiki/Learned_helplessness


I get so tired of this dichotomy between nature and nurture. It’s both. Some people have more issues on the nurture side other people have more issues on the nature side. What’s needed is to look at this more holistically.

When I realized this I didn’t know how much my environment was affecting my bipolar disorder. Buy matching my nature in my nurture I’ve come along way and getting off of almost all my medications.


I agree with what you're saying but not the what neuroma is saying (or at least i don't think we know enough to make the claim). I don't think you are saying the same thing.


If it's an RNA test, doesn't that mean it's just testing for the genetic predisposition? Unless depression is wholly genetic it seems weird to use an RNA test to diagnose it.

Edit: forgot my biology, testing for levels of RNA is probably pretty close to testing protein production.


> “Correlation doesn’t imply causation, but it does waggle its eyebrows suggestively and gesture furtively while mouthing ‘look over there.’” - Randall Munroe

The way I see this is that it might be one of those tests that, if they come back positive, indicate that further analysis should be made. A general practitioner might ask for this test and then recommend to the person to see a specialist.


Well, as said, the article suggests that this is a novel approach, but similar markers have been known to exist for a while and they still aren't used in diagnosis simply because they're typically not more indicative than simply the patient verbally enunciating “I feel bad.”.


This would, however, make a difference with people with mental illness. I make a distinction here between mental health and mental illness. I have been given so many different types of medications to manage so many different types of catecholamines, but they never know which catecholamines are higher low. I have bipolar disorder, it’s genetic, it’s in my family. If they could tell me what I needed to bring me down or take me up that would help me Tremendously.


If these blood tests do end up being good predictors of depression, it will be very interesting to see how they apply to people who are suffering from similar symptoms that are not clinically depressed - for example, people who have just experienced the death of a loved one.


There was actually an exeption for people that lost someone in the DSM. Following long debates they ended up removing it.

What seems clear is that in a lot of cases depression seems to be a normal reaction to worsening life conditions and not merely a brain chemicals imbalance. So I think it's wise to remain careful around what can be considered a depression and whether it should be considered a symptom or a disease.

https://www.theguardian.com/society/2018/jan/07/is-everythin...


Let me add that many psychiatric conditions, more so than physical conditions, are continuous, not binary, with severity changing over time.


Psychiatric conditions are physical conditions.

You cannot have a change in mood with out changes in brain catecholamines. Catecholamines are physical.


Well, assuming the brain is somewhat similar to a computer, then there would exist a separation between "brain hardware" and "brain software". Just like a bug in Windows is not a bug in the hardware, even though it is measurable in terms of electrical signals if you care to look, it could be that there exist separate psychiatric/psychological conditions (problems with the brain software) vs physical conditions (problems with the brain's hardware, such as a tumor or a glandular abnormality).

They would both be measurable in physical terms, but that doesn't mean that they have to both be exactly the same thing. IF this vague notion were correct, it could mean that there could be separate diseases like "physical depressions" (that is, various defects of the body's hardware that cause abnormal amounts of certain neurotransmitters to be present in the brain, influencing thought that way) and "psychological depressions" (various mistakes in the thought process/software that cause problems with motivation/emotions/etc, that themselves also result in certain neurotransmitters being present in abnormal amounts).


> Well, assuming the brain is somewhat similar to a computer, then there would exist a separation between "brain hardware" and "brain software".

And both the assumption and conclusions are bizarre.

There is no such distinction in the brain and the distinction in, physical man-made, hardware is also not so clear.


> There is no such distinction in the brain

How do you know this? What else would the brain be if not a computer, and if you agree that it is a computer, why do you believe it doesn't have some equivalent of "software"?

> the distinction in, physical man-made, hardware is also not so clear

Sure, the distinction is somewhat fuzzy, though there can be clear cut cases as well.


> How do you know this? What else would the brain be if not a computer, and if you agree that it is a computer, why do you believe it doesn't have some equivalent of "software"?

Because not all computers have this distinction, the first man-made computers did not have this distinction and the distinction still isn't that clear.

“software” is simply the part the end-user is expected to be able to change. The F.S.F. simply defines it as everything stored in writable memory, but the distinction between writable and nonwritable memory is not even so clear.

The human brain doesn't have a distinction between writable and nonwritable memory, and memory is implemented in circuitry itself.

One can build a computer even today that has no distinction between software and hardware.


Well, any computer ultimately executes a program (a computation, to be more accurate), whether it is hard-wired in the hardware (as in an ASIC) or not. If you create an ASIC to compute 1 + 1 and it outputs 2, but you later find out that you needed an ASIC that computed 1 - 1, I would not call that a hardware problem, because the hardware is doing exactly what it was supposed to do - it's just not useful to you. A hardware problem is one where your 1+1 ASIC is outputting 3 when it gets hot enough, or one where the ASIC is not starting at all.

Another piece of evidence that suggests to me that certain psychiatric conditions originate not in the physical brain itself but more in the "computation" (what I called a software error earlier) is the way people can be trapped into cults or other abusive relationships, where they start exhibiting signs of mental illness without any direct physical changes (that is, no diet changes, no physical violence, no irradiation etc.).

The reason why I consider this distinction is important is that, if I am right, then there must be psychiatric conditions that should be fixable through discussion and improvements in thinking (therapy), and there must also be psychiatric conditions that can't be fixed in this way. We know for sure that the second category exists, as some psychiatric symptoms are the result of tumors in the brain and elsewhere in the body; the first category is slightly less clear, thought therapy is definitely an important part of many treatment regimens, with clinical data backing up its use.

The biggest problem today is that we can't reliably tell, in most cases, which type of disease you may have, and so which approach is appropriate.


You assume that they are “conditions” in the physical sense with a single defining cause because a psychiatrist at one point decided to award a name to a set of superficially similar symptoms.

“back pains” is not a physical condition; there is a plethora of different physical conditions that can result into such superficially similar symptoms and this is the flaw psychiatry as a discipline is often criticized of, the assumption that an approach which assumes a defining cause necessarily has merit absent any evidence of such a defining cause.


Why don't we have valid an reliable biomarkers for depression then?

What is a 'normal' level of catecholamines?

Not disagreeing that the mental/physical dichotomy is arbitrary.


Because currently it’s impossible to test the amount of catecholamines in the brain.

What is a normal level? well, you know it when you feel it. There is no normal level, I get what you mean, depression exists for a reason. As does mania. These are healthy responses when we come into contact with an external stimuli. The issue is with mental illness, not mental health. With mental illness the changes happen with no apparent environmental stimulus.


It is possible to test: https://en.wikipedia.org/wiki/Catecholamine#Testing_for_cate...

Somebody else stated it already better than I could: We do have a number of biomarkers for depression, the problem is they only correlate with the disease, so asking you how you feel in a structured way is still more indicative.


I said they’re impossible to test in the brain, not in the plasma. It’s a huge difference.

Even the serum tests for catecholamines vary so much that you have to take them specific times of the day. And it can in no way diagnosis depression or any other mood disorders through those test. There Are no biomarkers for depression right now that are widely tested or even tested minimally. I know, I asked for them all the time because I have bipolar disorder.


I would hope we can have a discussion about this topic rather than people just down voting. If anyone can explain to me how psychiatric conditions are not physical conditions, let me know.


I think the main objection is that what you are saying is technically true - all human conditions are physical in the sense that humans are immensely complex dynamical systems consisting of atoms, molecules, proteins, pathways etc.

However it's not helpful in terms of diagnosis and treatment, which is fundamentally different in many ways compared to physical conditions - and stigma is often a result of people no understanding the difference.

To make a really simplified example: If you break your leg, a doctor will do a test, an x-ray say, recognise the leg is broken and interfere directly in one way or another with the physical system that is your body. The conscious you is not a part of this process (this is a simplified example, it does make some difference).

If you 'break your mind,' again very simplified, because you are treated like sh*t at work, your parent dies, you are genetically predisposed and have no social net, and as a result develop depression, there is no (physical) test. The conscious you is a central part of the treatment. It is even thinkable to not treat the physical you but target your environment instead.

Again this is a simplified example with shortcomings. Also having read your replies I believe you wanted to simply highlight that the distinction physical/mental is arbitrary and it is.


" seems to be a normal reaction to worsening life conditions and not merely a brain chemicals imbalance"

Just to make a distinction here. Worsening life conditions will also cause a "chemical imbalance" so it would look the same. The problem with people who have a Mental Illness is that the mood changes appear without any "known" life changes, which makes it harder to find the cause.

For me it is diet and environment that seem to have caused most of my issues.

Depression is a symptom, always, since it is caused by something more fundamental.


This is what worries me.

I would say that they need to do an RNA test and a Genetic Test as well.

I have Bipolar Disorder and even I go through periods of remission. Looking at genetics might give a better clue about how the trauma may effect a person long term.

They really need to figure out how to test for these catecholamines in the brain...


More information and publication biography on the company's website. [1]

I'm not sure if I read this correctly, but part of their approach is to take biomarkers from suicide victims

  The validation step 3 is usually done in an independent cohort of clinically severe subjects (or, in the case of suicide, a cohort of suicide completers).
[1] https://mindxsciences.com/faq/


No, this was done with living subjects.


Oh, it is that bad... Terrible.


They should really use the perpetrators rather than the victims.


Here is the study:

https://www.nature.com/articles/s41380-021-01061-w

I have my genetics through 23andme and I have Bipolar Disorder. The one thing that stuck out at my in my genetics were my SNPs in SLC6A4, which is one of the markers they look at.


I’m fairly sure that this paper is the one alluded to in the original press release:

Le-Niculescu, H., Roseberry, K., Gill, S.S. et al.

Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs.

Mol Psychiatry (2021)

https://doi.org/10.1038/s41380-021-01061-w




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