[HN Gopher] Brain circuit scores identify clinically distinct bi...
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       Brain circuit scores identify clinically distinct biotypes in
       depression/anxiety
        
       Author : MBCook
       Score  : 74 points
       Date   : 2024-06-18 03:49 UTC (1 days ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | Spod_Gaju wrote:
       | 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 wrote:
         | > 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 wrote:
           | 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 wrote:
             | 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_ wrote:
               | 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-
               | neuroscien...
        
               | Spod_Gaju wrote:
               | > 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-
               | menta...
               | 
               | Best of luck because I objectively know the crap you are
               | dealing with.
        
             | virtue3 wrote:
             | 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 wrote:
             | 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.
        
             | johnchristopher wrote:
             | > 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-menta... (edit: interesting reading btw) could be
             | written ?
        
         | ajb wrote:
         | 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 wrote:
         | 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 wrote:
           | 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.
        
       | Liquix wrote:
       | 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 wrote:
         | Either is sufficient for a diagnosis, I'd imagine, since you're
         | looking at two sides of the same coin.
        
         | MBCook wrote:
         | I think this is B so far.
         | 
         | But even being able to do something objective m (an MRI) and
         | come up with a prediction that is halfway accurate would be a
         | big step forward.
         | 
         | Could this lead to A? Maybe, assuming it's confirmed. Or maybe
         | cause and effect is backwards.
         | 
         | Either way, it's _something_ i'm not sure we've had before.
        
       | hn_throwaway_99 wrote:
       | 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 wrote:
         | 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.
        
           | JohnMakin wrote:
           | > 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.
           | 
           | This kind of reasoning is completely faulty and rampant in
           | discussions that usually hold a fair amount of stigma towards
           | people experiencing mental health conditions (it's also
           | extremely insulting fyi).
           | 
           | I can have a headache, and there may be an unknown biological
           | mechanism, but that doesn't mean I'm not experiencing a
           | headache.
        
             | andoando wrote:
             | As I said "Thats not to say I don't think people truly have
             | physical issues".
             | 
             | I have diagnosed ADHD, and I take mental health very
             | seriously. I have zero such prejudice.
             | 
             | By "definite" things I mean, singular, physical causes
             | which can be pointed to.
        
               | JohnMakin wrote:
               | I understand that you believe this, I am merely pointing
               | out that the type of reasoning you're using is typically
               | seen in the type of psychiatric gatekeeping used in
               | discussions that are laden with stigma against people
               | experiencing mental conditions.
        
             | dfgtyu65r wrote:
             | I don't think that's entirely fair. There does seem to be
             | something distinct about mental disorders - namely, they
             | are defined by the symptoms.
             | 
             | With physical ailments, symptoms are surface manifestations
             | of an underlying physical cause. For example, fever and
             | fatigue in flu are the result of the influenza virus.
             | Crucially, you can have the physical cause without symptoms
             | (such as in the presymptomatic period), so the two are
             | dissociable. Even where the physical cause is unknown,
             | there's still this symptom-cause distinction.
             | 
             | In the case of mental disorders, they're essentially
             | defined by the symptoms. To have depression is to be
             | depressed. To have anxiety is to be anxious. What would it
             | even mean to have depression without being depressed?
             | 
             | While on some level these are physical in a sense (insofar
             | as they result from brain activity), I don't necessarily
             | think we should think about their cause in the same way as
             | a physical ailment.
             | 
             | More to the point, there's a much more obvious sociocultral
             | element to mental disorders. There's no 'objective' line
             | between being sad and being depressed so while we clearly
             | can and should treat depression, it seems to be very
             | different from other diseases.
             | 
             | None of this is to take away from the real suffering people
             | undergo with these disorders. I just don't think that
             | treating them through a strict biological-pathological lens
             | is as useful as people think it is.
        
               | jaggederest wrote:
               | > namely, they are defined by the symptoms.
               | 
               | This is what we see historically, in the 19th and early
               | 20th centuries, in "body medicine". We're just at an
               | earlier stage of understanding and treating psychiatric
               | disorders. I assume in a couple hundred years we'll look
               | back at the current state of the art as hopelessly
               | outmoded.
               | 
               | > In the case of mental disorders, they're essentially
               | defined by the symptoms. To have depression is to be
               | depressed. To have anxiety is to be anxious. What would
               | it even mean to have depression without being depressed?
               | 
               | What would it mean to have typhoid without an actual
               | fever? The disease is something else, some causative
               | factor that is not the actual symptom itself, but is no
               | less real for that.
               | 
               | > I just don't think that treating them through a strict
               | biological-pathological lens is as useful as people think
               | it is.
               | 
               | Agreed, but that's with the current state of the art. I
               | would be surprised indeed if by 2080 we didn't have a
               | different lens to view these things through.
        
           | jaggederest wrote:
           | ADHD in particular is located to very specific areas in the
           | brain. Primarily the dorsolateral prefrontal cortex and areas
           | in the cingulate cortex. We can see neuroanatomy differences
           | on scans, which, while not specific or sensitive enough for
           | diagnosis, are definitely real physical changes in the brain,
           | and they're pretty consistent across diagnosed vs baseline.
           | 
           | There are lots of psychiatric disorders where that doesn't
           | take place, but developmental neuropsychiatric disorders
           | don't fall under that "are they even alike at all" kind of
           | umbrella. In some kind of awful alternate universe we could
           | pretty reliably induce them with gamma knife surgery, for
           | example.
           | 
           | Depression is much easier to argue that it's a less specific
           | symptom of a larger constellation, with lots of causes and
           | lots of manifestations.
        
             | andoando wrote:
             | Can you point me to a study showing these brain scans being
             | different from those with diagnosed ADHD and not? The
             | evidence would furthermore have to show that this
             | difference is apparent not just from adhd vs non adhd but
             | adhd vs anxiety, depression etc. And lastly, are these
             | changes perhaps an affect of taking stimulants?
             | 
             | And how significant are these results? Are we talking about
             | a few percent difference? Are 10% of diagnoses ADHD shown
             | to have statistically significant differences, 20, 50, 90?
             | Depending on the figure, my criticism of the diagnostic
             | criteria remains. Because if it is a low figure like 10%,
             | that means 90% of the diagnoses aren't supported by any
             | scientific evidence.
             | 
             | From what I've been told, including professionals this
             | evidence does not exist.
             | 
             | I've also seen studies which indicate that psychiatric
             | evaluations are entirely inconsistent across physicians.
        
               | jaggederest wrote:
               | > The morphometric findings predicted an ADHD diagnosis
               | correctly up to 83% of all cases.
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391018/
               | 
               | It's not good enough for diagnosis - you want to hit 95+%
               | accuracy for diagnostic. And MRIs are extremely expensive
               | compared to 2-3 outpatient psychology appointments. But
               | it's real.
        
       | SubiculumCode wrote:
       | 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/nih...
        
         | SubiculumCode wrote:
         | 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
        
       | zzzeek wrote:
       | 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" ?
        
       | Zak wrote:
       | 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
        
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