10 ms·

Brain circuit scores identify clinically distinct biotypes in depression/anxiety

201 points by MBCook 2y ago

Spod_Gaju 2y ago
IS it just me or is this ridiculous? They separated people who were having different symptoms and they showed it in MRIs. All this does is prove that you can derive these brain "biotypes" without the MRI. Why is this new or special or needed? We need treatment, not more tests to tell us what we already know.
- johnchristopher 2y ago
  > All this does is prove that you can derive these brain "biotypes" without the MRI. From the article: > There is an urgent need to derive quantitative measures > We need treatment, not more tests to tell us what we already know. Testing for objective markers can/should lead to choosing the most adequate treatment faster than relying on self reported symptoms or subjective opinion from therapists (even if experienced or informed).
  - Spod_Gaju 2y ago
    My point is that this was a waste of effort and money. They just need to listen to us patients and stop thinking we cannot be objective. Whenever it comes to mental health people think there is a total loss of objectivity. All you have to do is look at the patient. Is there a need to get a brain scan to see if I am anxious if I am acting objectively anxious? This need to measure everything is almost pathological.
    - Youden 2y ago
      Patients generally can't be relied upon to be objective. There may be exceptions but patients will often say they don't have symptoms that they do and that they do have symptoms that they don't. Speaking as a patient myself. I wish there was a way I could get an objective test that spits out exactly what's wrong with me and which treatments are most effective. I've been through several psychiatrists and treatments and am yet to find something effective. I'm glad research like this is being done.
      - the_sleaze_ 2y ago
        It's always been interesting to me that psychiatrists and psychologists just have to sort of trust the story they're being told. Recently CVS and other pharmacies have started denying prescriptions from some telehealth based psychiatrists because they believe they're over-prescribing amphetamines. How do they know? This article also makes me think of the neurologist that unknowingly analyzed his own brain scan only to discover he was a psychopath. https://www.smithsonianmag.com/science-nature/the-neuroscientist-who-discovered-he-was-a-psychopath-180947814/ https://www.smithsonianmag.com/science-nature/the-neuroscien...
        Spod_Gaju 2y ago
        Am I "telling a story" when I am walking down the street taking pictures of people because I think they are working for the government and spying on me? The doctors "objectively" thought I was on drugs. And those tele-health centers are being shutdown because they do no legitimate screening and are pill farms. https://thehill.com/policy/healthcare/4723163-cdc-disruptions-adhd-medicine-after-100m-fraud-arrest/ https://thehill.com/policy/healthcare/4723163-cdc-disruption... So I feel you are confusing mental health and mental illness and confusing compassion with a profit making operation.
      - solikeppl 2y ago
        [dead]
      - Spod_Gaju 2y ago
        > Patients generally can't be relied upon to be objective. Neither can doctors, or researchers. They obviously see something wrong with you, as they did with me, so do we worry about their objectivity? No. Because bias and stigma. And if you are looking for answers, like I have been for 20 year, you might want to look at the role the purine pathway plays in mood disorders. Here is an article I wrote about it. https://christianbonanno.substack.com/p/what-caused-my-mental-illness https://christianbonanno.substack.com/p/what-caused-my-menta... Best of luck because I objectively know the crap you are dealing with.
    - virtue3 2y ago
      Honestly a lot of these diagnosis issues are incredibly difficult. depression with anxiety is dramatically more difficult to treat than either or. Bipolar can come across as ADHD in certain parts of the cycle or just usually depression. In fact, you can even have uni-polar depression that does not respond to traditional anti-depressants and you don't necessarily exhibit hypomanic episodes. Relying on patients to know and understand what they are experiencing other than "this is just normal I assume everyone else experiences this" is not reliable. Having something that can reliably diagnose and find markers for these conditions would be _huge_. I wade through whitepapers and books on this stuff because of my own issues. I don't expect the average person to even remotely know about all of this; it's a lot and very subtle. To add on to all of this, people tend to not seek treatment until there IS a problem. Sometimes this can be really life alteringly bad, sometimes it's benign. But it would be helpful if people could just "take a test" and know or at least have an idea. The issue with being "objective" is also that your doctor has to be "objective" and I've had a lot of friends that are clearly ADHD and end up with DRs that think they are just trying to get medication and don't have ADHD. Worse yet; they do get medications and they have to cycle a few different ones because of the way they tolerate it. It would be really nice if we had an idea to correlate your ADHD, your body chemistry, and which drugs would be most effective for you rather than the 3-12 month ordeal of figuring that out.
    - webnrrd2k 2y ago
      It's true that doctors should listen to patients, and that diagnosing medical problems, especially psychological problems, can be very difficult. However, your post has a very "we don't need x-rays, we can just tell the bone is broken" vibe. It reads like you think better and more objective, quantitative diagnosis is not worth pursuing.
      - Spod_Gaju 2y ago
        I do not care about your vibe. I care about finding the truth and telling it like it is from my lived experience. They diagnosed the patients to get them in the study and they they said "see, it matched out "objective" diagnosis based on the patients "subjective" complaints. There is nothing quantitative about what they are doing. Take a look at figure 5. How quantitative is that?
    - johnchristopher 2y ago
      > This need to measure everything is almost pathological. What's pathological is the tendency to see everything in black or white, right or wrong. There are many different causes for fatigue and tiredness: the flu, atypical depression, chronic fatigue, etc. But those conditions can overlap with depression. Putting the symptoms through a sieve by eliminating some causes helps pinpoint the origin (I over-simplify of course). edit: this complaint about measuring things is a bit surprising considering what needed to be measured so this article https://christianbonanno.substack.com/p/what-caused-my-mental-illness https://christianbonanno.substack.com/p/what-caused-my-menta... (edit: interesting reading btw) could be written ?
      - Spod_Gaju 2y ago
        You said it. The fact that they are just looking at the brain when it comes to mental illness, is, well, insane. If one becomes "depressed" when sick, why not investigate the immune dysregulation in depression? The only way out of a mental illness is personalized medicine but that is something no one care enough to provide.
      - Spod_Gaju 2y ago
        > Putting the symptoms through a sieve by eliminating some causes helps pinpoint the origin (I over-simplify of course). That is nothing close to what they are doing. Do you think they are going to be giving these scans to everyone that walk in with fatigue and/or depression? I cannot even get to see a rheumatologist and I am disabled with schizoaffective disorder.
- ajb 2y ago
  From the article: "To enable more precise diagnosis and selection of the best treatment for each individual, we need to dissect the heterogeneity of depression and anxiety. The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive and frustrating, with 30–40% of patients not achieving remission after trying one treatment"
- funnym0nk3y 2y ago
  Depression presents with many symptoms, some of the are mutually exclusive. Take for example psychomotor changes. It could be retarded or agitated. Some people have anxiety, some don't. Some are irritable, some sleep very much and some sleep very little. There have been the classifications of melancholic and atypical depression, but they aren't used very often as many patients have features of both. Now consider the poor response to available medication (IIRC 30% remit and 60% respond, which leaves roughly 40% with a potential deadly disease without medication). Some symptoms of depression occur in other mental illnesses, like the similarity between bipolar and unipolar depression. Maybe the disease we currently call depression is acutally a cluster of diseases. That's the reason to look for biomarkers that separate those different diseases and the develop treatments specifically for one disease. Similar to the development of brexanolone for postpartum depression.
  - MBCook 2y ago
    Right. What if this were to be conformed and we could find out that A is best treated by Prozac but C responds really badly to it? Right now we just try lots of drugs, one after another, on each patient until something works or the patient gives up. What if we could confidently predict the drugs that were the most likely to succeed for each group? It may cut treatment times and help people find relief faster. Even if we don’t find new treatments or gain a better understanding of cause/effect it could still be useful.
  - Spod_Gaju 2y ago
    You are talking like there are medical treatments that work for those of us with mental illness. There are not. They only have medication to treat the symptoms. I am one of the people with this deadly disease and frankly I want to die right now because I am homeless living with schizoaffective disorder and it its the 15 year anniversary of my nephews suicide and all anyone here does is downvote me because they cannot take the time to listen. DO you know how many years I have heard of sht like this and then I go to the doctor and I am getting the same medications my mother got when she was sick 60 years ago? Do me a favor, read my blog, look at what I know and what I have and am living with, then come back here and tell me I should be happy about this study that will do nothing for me and nothing for anyone in the next 20 years. Then tell me how not giving me that money to help me other people living with mental illness who are homeless to find housing is not better. https://christianbonanno.substack.com/p/for-alex https://christianbonanno.substack.com/p/for-alex
Liquix 2y ago
how is causality established? the data seems to support either conclusion: A.) we found the types of brains that are inherently prone to depression/anxiety B.) we found the patterns that depressive/anxious thoughts make on MRIs
- jvanderbot 2y ago
  Either is sufficient for a diagnosis, I'd imagine, since you're looking at two sides of the same coin.
  - tsimionescu 2y ago
    Both could help for a diagnosis, but the first one also helps with finding treatments, the second one doesn't.
    - jvanderbot 2y ago
      Not so! The gold standard treatment includes CBT, which acts on thought patterns. Trying to separate thoughts from the physical brain wiring is futile - there is no disconnected "thought" that is _not_ the wiring of the brain. Changing thoughts does change brain, and changing brain does change thoughts.
      - tsimionescu 2y ago
        I'm not sure how that helps. If we identify the precise biological markers that correspond to depressed feelings, does that help us in some way to change them? We already know these people have depressive emotions, it's not like this test would reveal something we didn't know about them. There is clear value in this from the scientific side, but I don't see how it would help with treatment more directly. Conversely, if we find biological signs that are not directly related to currently experiencing depressive thoughts, those could be a promising target for medication/therapy, and could help detect depression earlier or in more borderline cases.
        2y ago
hn_throwaway_99 2y ago
I think this research is great. I've often said (and I'm sure I heard it somewhere else first) "Depression is not a disease, it's a symptom". The treatment for depression is kind of "throw stuff against the wall and see what works", because while different treatments target different parts of the brain, if someone comes in with depression we often don't know what the underlying etiology of that depression is. I suffer(ed) from chronic depression, and I'd get "bouts" of severe episodes every 5-6 years or so. I was very fortunate in that ketamine infusion therapy was a complete and amazing godsend for me - it was like it fixed a switch in my head. But I know other people with chronic depression that did ketamine therapy that got no benefit (but at least in one case they did get a lot of benefit from a different treatment, TMS, transcranial magnetic stimulation). My point is that basically everyone in the field of psychiatry knows that some interventions work great for some people while having no effect on others. More research like this should allow us to better target treatments.
- andoando 2y ago
  I think the same is true for all the psychiatric disorders, but people talk about diagnosing and "having" these disorders as if they're definite things. I don't understand for example why ADHD is any more real than any other collection of seemingly related symptoms one might conjure up. Just going by the criteria of the DSM, its logically possible for two people to be diagnosed while sharing only 3 of the 9 symptoms. And if one someone without ADHD can have 5/9 symptoms, and someone with ADHD can have the first 6 symptoms, and another can have the last 6, and another 1,3,5,7,8,9 of the symptoms, it says to me these symptoms can arise out of completely independent causes. So might it be possible someone meeting the clinical definition of ADHD can have just happen to have 6 independently caused symptoms? Thats not to say I don't think people truly have physical issues, but there is nothing at all to say any two people who "have" depression or ADHD are anything at all alike.
  - _yb2s 2y ago
    All of the symptoms of ADHD are different areas of executive control. I would argue that all people with ADHD generally also show all of the symptoms, but which are severe enough to cause a diagnosis varies- often due to external factors, like which aspects of executive control are most critical for a particular individual. People also have varying success and abilities at compensation. For example, I don’t misplace objects as often as a lot of people with ADHD, but that it just because I did it so much as a kid, I developed systems to deal with it- like the habit of anxiously accounting for everything I’m supposed to have on me every time I stand from a seated position. You might say I don’t even have that symptom, yet I can’t stand up and walk without checking everything in my pockets like most people can.
SubiculumCode 2y ago
I am finding the article frustrating to read, as the methods to derive the six networks is in an older paper [1][pdf link] Its basically: a) Use Neurosynth.org to perform metanalytic analysis associated with these search terms: “Default Mode, Salience, Attention, Threat, Reward, and Cognitive Control" Neurosynth is awesome, check it out. b) Resulting region pairs were quantified for intrinsic functional connectivity after regressing out task effects. * I don't understand the word 'pairs' here since Neurosynth does not provide pairs of anything (i.e. ROI's), unless they mean pairs of voxels. c) quote: then it gets really messy with : "o identify regions of interest (B) we considered the default mode, salience, and attention circuits to be task-free and the negative affect, positive affect, and cognitive control circuits to be task-evoked (details in Table S3). We refined our circuit features by first excluding regions based on low tSNR and low fit to gray matter (C). We evaluated internal consistency and excluded region pairs whose connectivity showed stronger associations with out-of-circuit region pairs than within-circuit region pairs in our healthy sample (E). From the resulting set of regions (E) we identified the subset implicated in hypothesized dysfunction and derived circuit clinical scores references to a healthy sample (F; details in Table S5)." [1][pdf link] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511971/pdf/nihms-1738043.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511971/pdf/nih...
- SubiculumCode 2y ago
  To be clear, I am not dissing the work..there were just a lot of steps they used to identify key regions of interest in size networks and then constrict those further to ones associated with depression and anxiety, and that process seems murky to me. This can totally be understandable situation: there are lots of decision that can be made in preprocessing and analysis, and not all get expanded on in a paper, and not an indication of p-hacking or anything. Importantly, they provide data and ROI masks so that others can examine this in their own datasets: https://github.com/leotozzi88/cluster_study_2023 https://github.com/leotozzi88/cluster_study_2023
- thereticent 2y ago
  Pairs of nodes, I believe. The connectivity is usually an edge weight between the ROI "nodes," the graph points.
zzzeek 2y ago
Study is very dense. Did the study show that SSRI and other antidepressants change brain chemistry? That is, are we finally done with "SSRIs are essentially placebos" ?
- tsimionescu 2y ago
  I don't think there is any doubt that SSRIs change brain chemistry, at least temporarily. The risk of causing serotoninergic syndrome should be proof enough of that. The question is whether their mechanism of action truly helps in people with depression disorders or anxiety disorders or any of the other conditions they are prescribed for. We clearly know from clinical trials that it helps some, at least somewhat, and it doesn't help at all or even hurts in many others; and this remains true regardless of dose. We don't have any specific theory as to why this is.
  - user_7832 2y ago
    IIRC it was found that the anti-inflammatory effects of SSRIs are partially responsible for their benefits
Zak 2y ago
This is the kind of result I expected to see after reading that antidepressant drugs are highly effective in about 15% of patients and relatively ineffective for everyone else. https://news.ycombinator.com/item?id=34337529 https://news.ycombinator.com/item?id=34337529
- H8crilA 2y ago
  Two things worth adding: it's not exactly the same ~15% for each drug, and it's a net +15% over placebo or even over doing nothing.
rlhf 2y ago
This approach may be the groundbreaking as it moves beyond traditional symptom-based classifications, allowing for more precise diagnosis and personalized treatment strategies. However, people in diseases may ignore their symptom and pretended nothing wrong with them.
slibhb 2y ago
Whenever I see results like this, I wonder if these scientists can diagnose depression with an MRI. It would be pretty easy to do that experiment, and my sense is that we just aren't there yet. And so I wonder if experiments like this are just measuring noise.
- theGnuMe 2y ago
  The cluster analysis they used means that we could train a CNN or transformer model to classify and it would be straightforward. I mean you can classify based on the clusters already. A transformer model would be interesting because you can map voxels to tokens and then look for patterns there. The embeddings alone would be interesting. Then there are generative AI approaches that can be integrated in as well. There's a few free ideas for anyone interested. Neat stuff!
- gnz11 2y ago
  You might enjoy this book [1] which dives into the questions you are asking. [1] https://lisafeldmanbarrett.com/books/how-emotions-are-made/ https://lisafeldmanbarrett.com/books/how-emotions-are-made/
hkt 2y ago
I'm immediately put in mind of the double empathy paper: https://www.tandfonline.com/doi/abs/10.1080/09687599.2012.710008 https://www.tandfonline.com/doi/abs/10.1080/09687599.2012.71... Specifically: do some combinations of biotypes struggle to relate to one another in the same way as autistic/non-autistic pairs do? Fascinating research regardless and I look forward to more people lifting the veil on the blobs of symptoms we think of as illnesses to get at the (seemingly highly varied) things that drive them.

201 points by MBCook 2y ago

IS it just me or is this ridiculous? They separated people who were having different symptoms and they showed it in MRIs. All this does is prove that you can derive these brain "biotypes" without the MRI. Why is this new or special or needed? We need treatment, not more tests to tell us what we already know.

johnchristopher 2y ago
> All this does is prove that you can derive these brain "biotypes" without the MRI. From the article: > There is an urgent need to derive quantitative measures > We need treatment, not more tests to tell us what we already know. Testing for objective markers can/should lead to choosing the most adequate treatment faster than relying on self reported symptoms or subjective opinion from therapists (even if experienced or informed).
- Spod_Gaju 2y ago
  My point is that this was a waste of effort and money. They just need to listen to us patients and stop thinking we cannot be objective. Whenever it comes to mental health people think there is a total loss of objectivity. All you have to do is look at the patient. Is there a need to get a brain scan to see if I am anxious if I am acting objectively anxious? This need to measure everything is almost pathological.
  - Youden 2y ago
    Patients generally can't be relied upon to be objective. There may be exceptions but patients will often say they don't have symptoms that they do and that they do have symptoms that they don't. Speaking as a patient myself. I wish there was a way I could get an objective test that spits out exactly what's wrong with me and which treatments are most effective. I've been through several psychiatrists and treatments and am yet to find something effective. I'm glad research like this is being done.
    - the_sleaze_ 2y ago
      It's always been interesting to me that psychiatrists and psychologists just have to sort of trust the story they're being told. Recently CVS and other pharmacies have started denying prescriptions from some telehealth based psychiatrists because they believe they're over-prescribing amphetamines. How do they know? This article also makes me think of the neurologist that unknowingly analyzed his own brain scan only to discover he was a psychopath. https://www.smithsonianmag.com/science-nature/the-neuroscientist-who-discovered-he-was-a-psychopath-180947814/ https://www.smithsonianmag.com/science-nature/the-neuroscien...
      - Spod_Gaju 2y ago
        Am I "telling a story" when I am walking down the street taking pictures of people because I think they are working for the government and spying on me? The doctors "objectively" thought I was on drugs. And those tele-health centers are being shutdown because they do no legitimate screening and are pill farms. https://thehill.com/policy/healthcare/4723163-cdc-disruptions-adhd-medicine-after-100m-fraud-arrest/ https://thehill.com/policy/healthcare/4723163-cdc-disruption... So I feel you are confusing mental health and mental illness and confusing compassion with a profit making operation.
    - solikeppl 2y ago
      [dead]
    - Spod_Gaju 2y ago
      > Patients generally can't be relied upon to be objective. Neither can doctors, or researchers. They obviously see something wrong with you, as they did with me, so do we worry about their objectivity? No. Because bias and stigma. And if you are looking for answers, like I have been for 20 year, you might want to look at the role the purine pathway plays in mood disorders. Here is an article I wrote about it. https://christianbonanno.substack.com/p/what-caused-my-mental-illness https://christianbonanno.substack.com/p/what-caused-my-menta... Best of luck because I objectively know the crap you are dealing with.
  - virtue3 2y ago
    Honestly a lot of these diagnosis issues are incredibly difficult. depression with anxiety is dramatically more difficult to treat than either or. Bipolar can come across as ADHD in certain parts of the cycle or just usually depression. In fact, you can even have uni-polar depression that does not respond to traditional anti-depressants and you don't necessarily exhibit hypomanic episodes. Relying on patients to know and understand what they are experiencing other than "this is just normal I assume everyone else experiences this" is not reliable. Having something that can reliably diagnose and find markers for these conditions would be _huge_. I wade through whitepapers and books on this stuff because of my own issues. I don't expect the average person to even remotely know about all of this; it's a lot and very subtle. To add on to all of this, people tend to not seek treatment until there IS a problem. Sometimes this can be really life alteringly bad, sometimes it's benign. But it would be helpful if people could just "take a test" and know or at least have an idea. The issue with being "objective" is also that your doctor has to be "objective" and I've had a lot of friends that are clearly ADHD and end up with DRs that think they are just trying to get medication and don't have ADHD. Worse yet; they do get medications and they have to cycle a few different ones because of the way they tolerate it. It would be really nice if we had an idea to correlate your ADHD, your body chemistry, and which drugs would be most effective for you rather than the 3-12 month ordeal of figuring that out.
  - webnrrd2k 2y ago
    It's true that doctors should listen to patients, and that diagnosing medical problems, especially psychological problems, can be very difficult. However, your post has a very "we don't need x-rays, we can just tell the bone is broken" vibe. It reads like you think better and more objective, quantitative diagnosis is not worth pursuing.
    - Spod_Gaju 2y ago
      I do not care about your vibe. I care about finding the truth and telling it like it is from my lived experience. They diagnosed the patients to get them in the study and they they said "see, it matched out "objective" diagnosis based on the patients "subjective" complaints. There is nothing quantitative about what they are doing. Take a look at figure 5. How quantitative is that?
  - johnchristopher 2y ago
    > This need to measure everything is almost pathological. What's pathological is the tendency to see everything in black or white, right or wrong. There are many different causes for fatigue and tiredness: the flu, atypical depression, chronic fatigue, etc. But those conditions can overlap with depression. Putting the symptoms through a sieve by eliminating some causes helps pinpoint the origin (I over-simplify of course). edit: this complaint about measuring things is a bit surprising considering what needed to be measured so this article https://christianbonanno.substack.com/p/what-caused-my-mental-illness https://christianbonanno.substack.com/p/what-caused-my-menta... (edit: interesting reading btw) could be written ?
    - Spod_Gaju 2y ago
      You said it. The fact that they are just looking at the brain when it comes to mental illness, is, well, insane. If one becomes "depressed" when sick, why not investigate the immune dysregulation in depression? The only way out of a mental illness is personalized medicine but that is something no one care enough to provide.
    - Spod_Gaju 2y ago
      > Putting the symptoms through a sieve by eliminating some causes helps pinpoint the origin (I over-simplify of course). That is nothing close to what they are doing. Do you think they are going to be giving these scans to everyone that walk in with fatigue and/or depression? I cannot even get to see a rheumatologist and I am disabled with schizoaffective disorder.
ajb 2y ago
From the article: "To enable more precise diagnosis and selection of the best treatment for each individual, we need to dissect the heterogeneity of depression and anxiety. The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive and frustrating, with 30–40% of patients not achieving remission after trying one treatment"
funnym0nk3y 2y ago
Depression presents with many symptoms, some of the are mutually exclusive. Take for example psychomotor changes. It could be retarded or agitated. Some people have anxiety, some don't. Some are irritable, some sleep very much and some sleep very little. There have been the classifications of melancholic and atypical depression, but they aren't used very often as many patients have features of both. Now consider the poor response to available medication (IIRC 30% remit and 60% respond, which leaves roughly 40% with a potential deadly disease without medication). Some symptoms of depression occur in other mental illnesses, like the similarity between bipolar and unipolar depression. Maybe the disease we currently call depression is acutally a cluster of diseases. That's the reason to look for biomarkers that separate those different diseases and the develop treatments specifically for one disease. Similar to the development of brexanolone for postpartum depression.
- MBCook 2y ago
  Right. What if this were to be conformed and we could find out that A is best treated by Prozac but C responds really badly to it? Right now we just try lots of drugs, one after another, on each patient until something works or the patient gives up. What if we could confidently predict the drugs that were the most likely to succeed for each group? It may cut treatment times and help people find relief faster. Even if we don’t find new treatments or gain a better understanding of cause/effect it could still be useful.
- Spod_Gaju 2y ago
  You are talking like there are medical treatments that work for those of us with mental illness. There are not. They only have medication to treat the symptoms. I am one of the people with this deadly disease and frankly I want to die right now because I am homeless living with schizoaffective disorder and it its the 15 year anniversary of my nephews suicide and all anyone here does is downvote me because they cannot take the time to listen. DO you know how many years I have heard of sht like this and then I go to the doctor and I am getting the same medications my mother got when she was sick 60 years ago? Do me a favor, read my blog, look at what I know and what I have and am living with, then come back here and tell me I should be happy about this study that will do nothing for me and nothing for anyone in the next 20 years. Then tell me how not giving me that money to help me other people living with mental illness who are homeless to find housing is not better. https://christianbonanno.substack.com/p/for-alex https://christianbonanno.substack.com/p/for-alex

Liquix 2y ago

how is causality established? the data seems to support either conclusion: A.) we found the types of brains that are inherently prone to depression/anxiety B.) we found the patterns that depressive/anxious thoughts make on MRIs

jvanderbot 2y ago
Either is sufficient for a diagnosis, I'd imagine, since you're looking at two sides of the same coin.
- tsimionescu 2y ago
  Both could help for a diagnosis, but the first one also helps with finding treatments, the second one doesn't.
  - jvanderbot 2y ago
    Not so! The gold standard treatment includes CBT, which acts on thought patterns. Trying to separate thoughts from the physical brain wiring is futile - there is no disconnected "thought" that is _not_ the wiring of the brain. Changing thoughts does change brain, and changing brain does change thoughts.
    - tsimionescu 2y ago
      I'm not sure how that helps. If we identify the precise biological markers that correspond to depressed feelings, does that help us in some way to change them? We already know these people have depressive emotions, it's not like this test would reveal something we didn't know about them. There is clear value in this from the scientific side, but I don't see how it would help with treatment more directly. Conversely, if we find biological signs that are not directly related to currently experiencing depressive thoughts, those could be a promising target for medication/therapy, and could help detect depression earlier or in more borderline cases.
      - 2y ago

hn_throwaway_99 2y ago

I think this research is great. I've often said (and I'm sure I heard it somewhere else first) "Depression is not a disease, it's a symptom". The treatment for depression is kind of "throw stuff against the wall and see what works", because while different treatments target different parts of the brain, if someone comes in with depression we often don't know what the underlying etiology of that depression is. I suffer(ed) from chronic depression, and I'd get "bouts" of severe episodes every 5-6 years or so. I was very fortunate in that ketamine infusion therapy was a complete and amazing godsend for me - it was like it fixed a switch in my head. But I know other people with chronic depression that did ketamine therapy that got no benefit (but at least in one case they did get a lot of benefit from a different treatment, TMS, transcranial magnetic stimulation). My point is that basically everyone in the field of psychiatry knows that some interventions work great for some people while having no effect on others. More research like this should allow us to better target treatments.

andoando 2y ago
I think the same is true for all the psychiatric disorders, but people talk about diagnosing and "having" these disorders as if they're definite things. I don't understand for example why ADHD is any more real than any other collection of seemingly related symptoms one might conjure up. Just going by the criteria of the DSM, its logically possible for two people to be diagnosed while sharing only 3 of the 9 symptoms. And if one someone without ADHD can have 5/9 symptoms, and someone with ADHD can have the first 6 symptoms, and another can have the last 6, and another 1,3,5,7,8,9 of the symptoms, it says to me these symptoms can arise out of completely independent causes. So might it be possible someone meeting the clinical definition of ADHD can have just happen to have 6 independently caused symptoms? Thats not to say I don't think people truly have physical issues, but there is nothing at all to say any two people who "have" depression or ADHD are anything at all alike.
- _yb2s 2y ago
  All of the symptoms of ADHD are different areas of executive control. I would argue that all people with ADHD generally also show all of the symptoms, but which are severe enough to cause a diagnosis varies- often due to external factors, like which aspects of executive control are most critical for a particular individual. People also have varying success and abilities at compensation. For example, I don’t misplace objects as often as a lot of people with ADHD, but that it just because I did it so much as a kid, I developed systems to deal with it- like the habit of anxiously accounting for everything I’m supposed to have on me every time I stand from a seated position. You might say I don’t even have that symptom, yet I can’t stand up and walk without checking everything in my pockets like most people can.

SubiculumCode 2y ago

I am finding the article frustrating to read, as the methods to derive the six networks is in an older paper [1][pdf link] Its basically: a) Use Neurosynth.org to perform metanalytic analysis associated with these search terms: “Default Mode, Salience, Attention, Threat, Reward, and Cognitive Control" Neurosynth is awesome, check it out. b) Resulting region pairs were quantified for intrinsic functional connectivity after regressing out task effects. * I don't understand the word 'pairs' here since Neurosynth does not provide pairs of anything (i.e. ROI's), unless they mean pairs of voxels. c) quote: then it gets really messy with : "o identify regions of interest (B) we considered the default mode, salience, and attention circuits to be task-free and the negative affect, positive affect, and cognitive control circuits to be task-evoked (details in Table S3). We refined our circuit features by first excluding regions based on low tSNR and low fit to gray matter (C). We evaluated internal consistency and excluded region pairs whose connectivity showed stronger associations with out-of-circuit region pairs than within-circuit region pairs in our healthy sample (E). From the resulting set of regions (E) we identified the subset implicated in hypothesized dysfunction and derived circuit clinical scores references to a healthy sample (F; details in Table S5)." [1][pdf link] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511971/pdf/nihms-1738043.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9511971/pdf/nih...

SubiculumCode 2y ago
To be clear, I am not dissing the work..there were just a lot of steps they used to identify key regions of interest in size networks and then constrict those further to ones associated with depression and anxiety, and that process seems murky to me. This can totally be understandable situation: there are lots of decision that can be made in preprocessing and analysis, and not all get expanded on in a paper, and not an indication of p-hacking or anything. Importantly, they provide data and ROI masks so that others can examine this in their own datasets: https://github.com/leotozzi88/cluster_study_2023 https://github.com/leotozzi88/cluster_study_2023
thereticent 2y ago
Pairs of nodes, I believe. The connectivity is usually an edge weight between the ROI "nodes," the graph points.

zzzeek 2y ago

Study is very dense. Did the study show that SSRI and other antidepressants change brain chemistry? That is, are we finally done with "SSRIs are essentially placebos" ?

tsimionescu 2y ago
I don't think there is any doubt that SSRIs change brain chemistry, at least temporarily. The risk of causing serotoninergic syndrome should be proof enough of that. The question is whether their mechanism of action truly helps in people with depression disorders or anxiety disorders or any of the other conditions they are prescribed for. We clearly know from clinical trials that it helps some, at least somewhat, and it doesn't help at all or even hurts in many others; and this remains true regardless of dose. We don't have any specific theory as to why this is.
- user_7832 2y ago
  IIRC it was found that the anti-inflammatory effects of SSRIs are partially responsible for their benefits

Zak 2y ago

This is the kind of result I expected to see after reading that antidepressant drugs are highly effective in about 15% of patients and relatively ineffective for everyone else. https://news.ycombinator.com/item?id=34337529 https://news.ycombinator.com/item?id=34337529

H8crilA 2y ago
Two things worth adding: it's not exactly the same ~15% for each drug, and it's a net +15% over placebo or even over doing nothing.

rlhf 2y ago

This approach may be the groundbreaking as it moves beyond traditional symptom-based classifications, allowing for more precise diagnosis and personalized treatment strategies. However, people in diseases may ignore their symptom and pretended nothing wrong with them.

slibhb 2y ago

Whenever I see results like this, I wonder if these scientists can diagnose depression with an MRI. It would be pretty easy to do that experiment, and my sense is that we just aren't there yet. And so I wonder if experiments like this are just measuring noise.

theGnuMe 2y ago
The cluster analysis they used means that we could train a CNN or transformer model to classify and it would be straightforward. I mean you can classify based on the clusters already. A transformer model would be interesting because you can map voxels to tokens and then look for patterns there. The embeddings alone would be interesting. Then there are generative AI approaches that can be integrated in as well. There's a few free ideas for anyone interested. Neat stuff!
gnz11 2y ago
You might enjoy this book [1] which dives into the questions you are asking. [1] https://lisafeldmanbarrett.com/books/how-emotions-are-made/ https://lisafeldmanbarrett.com/books/how-emotions-are-made/

hkt 2y ago

I'm immediately put in mind of the double empathy paper: https://www.tandfonline.com/doi/abs/10.1080/09687599.2012.710008 https://www.tandfonline.com/doi/abs/10.1080/09687599.2012.71... Specifically: do some combinations of biotypes struggle to relate to one another in the same way as autistic/non-autistic pairs do? Fascinating research regardless and I look forward to more people lifting the veil on the blobs of symptoms we think of as illnesses to get at the (seemingly highly varied) things that drive them.