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Brain circuit scores identify clinically distinct biotypes in depression/anxiety (nature.com)
201 points by MBCook 13 days ago | hide | past | favorite | 95 comments





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.


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.


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.


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.


> 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.


> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391018/

Two major problems with studies like this:

1. The number of brain sub-regions and associated variables they're looking at is huge. Perhaps more than the number of patients in the study, depending on how you look at the data. If you collect enough data points on two groups of about ~30 people each and you run enough regressions, eventually you'll find some model that works on your small data set. This would need to be tested against a much larger cohort.

2. They did not control for stimulant usage at all. In fact, they note that stimulant use was vastly higher in the ADHD group, because obviously you need an ADHD diagnosis to receive ongoing stimulant prescriptions. It's a delicate topic, but we know that stimulant use in some cases is associated with changes in brain structure and blood flow. It's a huge variable that is hard to control for in a study like this.

Overall, I don't find a study with 31 ADHD patients that tested dozens and dozens of different variables to be all that conclusive. Perhaps useful for focusing future research, but a singular study like this isn't very conclusive.


I think there's also another critical issue that plagues every single observational study - the direction of causality. Our behaviors can and do physically change every single aspect of our body, including our brains. For instance chess masters not only activate different parts of their brain when playing chess than amateurs, but also have observable morphometric differences in their brains. [1]

If the direction of causality there was not overtly obvious (as nobody starts out anything even close to a master), one could easily assume those differences caused one to be a master, rather than vice versa. It's the exact same issue here, except the direction of causality is unclear. You're seeing a shared morphometric difference among people of some trait (ADHD) and then just assuming that that difference causes ADHD, rather than that ADHD causes the difference!

To even assume this is the case one would need to perform MRIs on random very young individuals prior to ADHD diagnoses, and then make a prediction, based solely on that MRI, on which ones would be diagnosed with ADHD with no input or information given to the participants before a follow study in a decade or so. That study would then help prove the direction of causality that's seemingly just simply being assumed in this one.

[1] - https://www.frontiersin.org/journals/neuroscience/articles/1...


In a world where we had precision tools that could be used to deliberately alter brain morphology, the direction of causality would be highly relevant for trying to treat ADHD -- it would tell us whether there is any point in trying to use those tools. But for diagnosis only, I don't think the direction is actually relevant. That is, if we see a strong correlation between ADHD behaviour (as measured by, say, a standardised written test) and certain brain morphologies, then we're justified in concluding that ADHD has some objective physical manifestation -- that is, that the written tests aren't just measuring arbitrary collections of symptoms, they're estimating "something real". There might still be many different underlying causes.

Would this be useful? I think so: It would then be possible to assess the accuracy of a written test.

I think the risk of conflation with stimulant use that another poster mentioned is very real, though, and that problem is a close cousin of the "direction of causality" problem.


This is true and quite an interesting and nuanced point. But the connotation of this discussion, and something I expect applies to the overwhelming majority of people, is an association of physical manifestation (brain morphometrics or whatever) causes issue, rather than issue causes physical manifestation.

In particular this whole thread of discussion started back with somebody expressing a bit of skepticism about the definitive nature of ADHD (and other psychiatric disorders) and somebody responded with the brain morphometrics as proof of such, yet in reality that's mostly still just begging the question.


According to this, stimulant use if anything normalizes the differences found. Without a proper understanding of the field, I have to admit its hard to criticize the specifics. https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2...

That said, all these studies are done way after ADHD was established. That is, ADHD as a concept wasn't established by looking at neurological brain scans or any kind of physical evidence. Makes me wonder what the exact thought process was for establishing the DSM.

I still feel like if I made up a disorder by coming up with 9 semi-normal behaviors as symptoms, enough people would just by chance meet most of the criteria, and imaging scans would find some difference. Wish I was rich so I could conduct that experiment myself.


I admit the study looks pretty good, but Id still have to see if these changes are present in those with depression/anxiety, etc and 2. are not result of stimulant use to be convinced. I found this if youre interested which cites more studies https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2...

>It's not good enough for diagnosis - you want to hit 95+% accuracy for diagnostic.

This doesn't quite make sense to me, because you're comparing it to the current diagnostic criteria and assuming it to be 100% accurate.

If we want to be totally scientific, we ought to just do these scans and diagnose people with low gray matter volume, etc and drop the DSM, ADHD etc.


And if we start scanning tons of brains and finding out that X% of people with low gray matter volume do not exhibit any ADHD symptoms?

Bayes strikes again.

Unfortunately, the topic of ADHD and brain imaging has been full of bad research and grifters. At the extreme end, people like Dr. Amen were writing books about how ADHD and neuroimaging were correlated, which turned into attempts to sell SPECT imaging for ADHD purposes through his clinics.

Using brain imaging to push questionable psychiatry premises was very popular for a while, and you need to take a lot of research from that era with a huge grain of salt. Remember that with the right settings, neuroscientists can even produce images showing activity in brain regions of completely dead salmon: https://www.wired.com/2009/09/fmrisalmon/


Quite. Psychiatry loves to talk about brain scans and neuroanatomy, but until it dares to actually use them for diagnosis, I think it should be regarded as window dressing.

And you should always read these studies with a careful eye to whether the ADHD subjects are medicated. Often the studies literally measure the effect of the medication and nothing else. (It's a cruel irony for schizophrenics, who are put on antipsychotics that shrivel the cerebral cortex, only to find their shrivelled cerebral cortex brandished as evidence of their supposed dysfunction.)

Also, note that fMRI does not and cannot indicate structural abnormalities in the brain. It just measures current brain activity, as revealed by the flow of magnetically-charged oxygenated blood through the brain. It tells us these people's brains are currently behaving differently from control subjects' brains. Which, it seems to me, is stating the bleeding obvious.


It's a shame that every time someone (e.g. upthread) mentions how even just MRIs are very expensive, often as an excuse for not using such tools, I think of all the times I've heard that other places like India make them quite cheap. Well, it's just one part of a giant pile of problems.

Thanks for the reminder about schizophrenics. Even though I've known about the effect (and especially the effect with use of lithium, which is thankfully not so commonly used), I've sort of forgotten about it as a factor in my thinking about the recent struggles of someone in my personal life. It's probably not forgotten by those working in the system, and wouldn't surprise me if it contributes to the incentives of the system encouraging people to be shut-ins and never challenge anything.


Yeah, I am very troubled by it. I had a friend staying with me last year who I hadn't realised was schizophrenic (a hopelessly vague diagnosis but he undoubtedly had parted company with reality) and off his meds. It was horribly sad. He killed himself a few months later. My mum is a psychiatrist and insists that third-generation antipsychotics are not a 'chemical cosh', which I find doubtful, seeing as so many schizophrenics seem to consider them a worse prospect than unmedicated schizophrenia or death.

We're now giving these drugs to autistics, I gather, and low-dose olanzapine is even being trialled for kids with Asperger's. Compared with lobotomy I suppose it requires less cleaning up.

Since you mention India, I should add that India and other poor countries manage to treat schizophrenia with better remission rates than the UK and US: https://www.nature.com/articles/508S14a


> 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.


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.


> 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.


Completely agree.

Imo we'll come to see that these categorizations of mental disorders are far too simplistic


I think the mind and body are fundamentally different. Like with diabetes you might have a genetic deficiency that interferes with producing insulin so you have diabetes. You inject insulin and now you don't, more or less.

The mind is much more of a complex system than that.


Well, there are also slower/faster acting insulins so that system is also more complex than that, but yeah you are generally right.

I like to think of it with an analogy like you have a very intricate 3D maze and have to get a tiny ball into a hole, but you can only ever move the maze in one direction, and it resets between tries. Something like SSRI just pushes everything one way in a big swipe, and sure it might just solve a particular puzzle, but there are endless others where such low-precision method has no way of succeeding. Of course that’s why psychotherapy is a must have for any sort of medication.


There is no fundamental difference between mind and body. You are seriously underestimating the complexity of the endocrine system.

> There does seem to be something distinct about mental disorders - namely, they are defined by the symptoms.

There a pretty long list of idiopathic physical ailments, and there are some mental disorders that have specific mechanisms. I get the generalization, but the reality is more jumbled.


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.


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.

“I understand that you believe” …that questioning diagnostic clarity is associated with some nebulous conversational or clinical scenarios that make you uncomfortable. But sticking your head in the epistemological sand and chastising people for being “extremely insulting” (based on your own extrapolated associations with their position) is extremely …condescending argument-by-assertion.

I have skin in the game on this one and in my own experience sloppy diagnostics have caused way more suffering than stigma. I was nodding along with gp’s entire point. Your confidently dismissive chastisement is what feels out of line.


I don’t really disagree with you other than to say that if your issue is with my tone and not my point, I don’t really have anything to say. Nothing I’ve said has been far off and I am speaking from a lot of experience here as a former admin of multiple large private mental health support groups. These arguments are all very much the same, and serving a very specific subtle purpose that does not actually advance discussion on this topic, and that is to cast doubt onto people suffering whethering they are “actually” suffering from whatever and therefore, in this hypercapitalist healthcare system (speaking of the USA specifically here), whether or not it is “worthy” of care, especially in the eyes of doctors that should know, who frequently have a high amount of control in these situations wrt to what care you are deemed “worthy” to receive.

Thus the result of these situations is many people cannot afford (or even if they can, sometimes no) proper care necessary to them. Gatekeeping types of arguments like these do not make that better.


What Ive seen from these support communities like /r/Adhd is admins gatekeeping their interpretations with this guise of knowing whats best for everyone.

The admins there for example have decided that 1. The word "neurotypical" is banned, 2. One cannot say adhd isnt a disorder / adhd might have benefits. 3. Discussing negatives of medication seems to be removed


ADHD forums are notorious for this. I do not personally moderate this way. Everyone’s opinions should be valid if they respect others. No one’s problems are any more special than anyone else’s, and if someone is displaying that type of behavior, they probably don’t belong in a support group.

ADHD in particular is further complicated by the fact that there are many, many drug seekers that game the system and even fool themselves. Even worse these drug seekers have collectively done alot to create scarcity in a limited supply of a class of drugs that many people think they need to survive - (i am making no comment about the efficacy of adhd meds) - so strong violent opinions are evoked (understandably). That is why these rules are in place. People simply cannot discuss the subject rationally. I do not try to involve myself in those communities, but many of the Autism spectrum disorder communities and depression support groups don’t suffer similar issues and people that try to gatekeep are promptly scolded. I do acknowledge adhd forums are a unique place for the reasons I mentioned above.


This gets to the quick of one half of the matter, and in another post you acknowledge the other half too -- the incentive that exists for healthy people to "game the system" (whether it be to get access to stimulants, or "just" sympathy).

I agree with almost everything you've written here, and have the same sympathies, except that I don't think it's legitimate to criticise the style of argument you criticise just because it's often used to subtly question whether people are "actually" suffering (and I agree that it is often used that way).


Why blame people skeptical of psychiatry for affordability issues when you could just blame big pharma? Wouldn't that actually make sense? The fact that you mention the former but not the latter makes you lose a lot of credibility

Or I guess, if you have skin in the game, it does make sense to criticize the people criticizing the game instead of the people perpetuating it

> in this hypercapitalist healthcare system (speaking of the USA specifically here), whether or not it is “worthy” of care

What's more hypercapitalist than this "ask your doctor" shit?

If I was a pharmaceutical company, it would be in my financial best interest to deem as many people eligible as possible. If I was an admin at some mental health thing somewhere, it would be in my financial best interest to make sure as many people buy into it as possible


I never advocated “ask your doctor shit”, whatever that means, and I think you have severely misunderstood the post you are responding to.

Regarding big pharma, they are certainly to blame, but you don’t really see similar types of discussions regarding purely physical ailments like cancer.

As I said in my comments I am approaching this as a moderator for mental health groups where this type of discussion frequently arises and to point out a line of reasoning I frequently have to deal with.


There's plenty of skepticism of corporate influence in health care. I am skeptical of anything where money is involved.

Cancer is an extreme example here because being 1. Based on hard physical evidence and 2. having a huge liability for misdiagnosis, doctors/hospitals would be in huge trouble if they diagnosed you with cancer and gave you chemo when you did not have it. This serves as a check against pharmaceutical interests.

Mental diagnoses/treatment on the other hand is mostly done in independent offices, private practices, and in prisons/institutions on committed people, and it carries very little risk if misdiagnosed. With adhd its even worse, because its often a diagnosis a patient seeks.

I really don't understand where you're coming from. It seems you don't want people to criticize psychiatry because it makes some people feel bad not having the validation of these disorders being a totally legit, agreed upon science?

I think that's taking the completely wrong angle, like I said I am diagnosed and I don't feel bad about it one bit despite all my opinions here.


> I am merely pointing out that the type of reasoning you’re using is typically seen in the type of psychiatric gatekeeping

You called this reasoning "completely faulty" in your previous comment, which clearly goes well beyond that.

What you are actually trying to do is stigmatise a valid form of reasoning, by association.


I understand the first sentence I've said "seems like" a statement made by with someone with prejudice saying something like "people with adhd are lazy". But as I clarified, my actual criticism is entirely different and I for one have never even seen it be mentioned.

We will never advance our understanding of psychiatry if we can't criticize it, and I for one definitely don't think we already perfected it.


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.

>All of the symptoms of ADHD are different areas of executive control.

I am not sure what you mean. Isn't "executive control" involved in almost every behavior? Why are the criteria used in ADHD diagnosis any more indicative of executive control than some other set of criteria I can come up with?

Is being bored of people talking a sign of lack of control or a lack of interest?

>I would argue that all people with ADHD generally also show all of the symptoms,

All people show all the symptoms. Who has never lost their keys, day dreamed during a conversation, loses focuses in an activity, forget small details, etc.

>yet I can’t stand up and walk without checking everything in my pockets like most people can.

How do you know what most people do? I think checking your pockets is a fairly common normal behavior. Different people have different adaptations to solving this problem of making sure they have what they need when they go out. Some people may have developed the discipline from a young age for example of placing things at the same place everytime. Some people may be more risk tolerant or care free, so they may not devote so much attention to the consequences of losing things. Some people may be clean freaks, so they encounter where their things are more often as they clean, and having a clean space, are also able to find things more easily. Some people, in some circumstances may become anxious, overly excited, etc before going out, and lose track of these things. There's a million reasons for why someone does these things.

These are all things that may even change by environment! I think the ADHD diagnosis can be harmful in that it makes people attribute all their behaviors to "Adhd" and makes them believe they are incapable of being changed.

And this is all contingent on even trusting that you actually do forget things more often than most, which again I don't know why people are so sure about, and Im even more confused as to how a physician assesses this to be true.


As someone formerly diagnosed with ADHD I tend to agree with you, but I thought there were studies which found specific genes and brain structures common to many people diagnosed with ADHD, I need to look in to this. On symptoms alone the overlap between trauma-noise and ADHD means someone with C-PTSD may share the symptoms of ADHD and vice versa but psychologists need only be aware of the conditions which are often confused and find criteria to rule one or the other out. There's no doubt that many of disorders/conditions in the DSM need more work to make them as helpful as they can possibly be, and for the world to recognize that they are clusters of symptoms not true things with firm borders (unless they turn out to be through neuro-science). Once certain issues become recurrent/troublesome enough to seek a diagnosis I only hope the DSM aligns people to something which is helpful, whether it be pharmicological or developing coping strategies. Some may find it invalidating for their DSM diagnosis to be questioned but it's not an attack on the validity of their problems, only on what the labels are referring to.

> Is being bored of people talking a sign of lack of control or a lack of interest?

Being bored is a sign of lack of interest- being unable to focus anyways when it is boring but critically important, and you are choosing to try to focus on it but still can't would be a sign of ADHD.

I hope this specific example illustrates what I mean about executive control, and answers your previous question as well. However, that is what connects the symptoms of ADHD- they are the most debilitating real world consequences or symptoms of a developmental delay in executive control. There are things other than ADHD that can permanently or temporarily inhibit executive control such as streptococcal infections and sleep deprivation, and cause a nearly identical list of symptoms.

> I think the ADHD diagnosis can be harmful in that it makes people attribute all their behaviors to "Adhd" and makes them believe they are incapable of being changed.

This is absolute nonsense, it's like saying that getting an X-ray is harmful, because if people know their leg is broken, it might make them think they can't walk on it like normal.

ADHD is highly treatable, and there is now a huge community of people with books, podcasts, etc. that share practical tips that work for people with ADHD- when regular productivity tips typically don't. Personally, I was undiagnosed as a child and constantly abused and called a lazy slacker by adults for not doing what I was supposed to- I desperately wanted to, and couldn't figure out what was wrong with me. I tried every productivity trick and study hack in dozens of books, and nothing worked at all, and I didn't understand why.

As an adult, I have learned about practical tricks from other people with ADHD, as well as medication that let me finally focus on the things I choose to focus on. It transformed my life from being a living hell, to being a successful person with a good life. The ADHD diagnosis allowed me to understand why the things I was doing to change weren't working, and realize I wasn't the only person trying to fix this on my own, but there are proven strategies.

The reality of ADHD can much more serious, and different than most people think, or the name implies. People with untreated ADHD have substantially shorter lifespans, have a huge number of other physical and mental health complications, and have a much lower quality of life. Yes, many people have mild versions of executive control challenges from time to time- and things like addictions and loss of sleep can cause them to be worse for anyone. However, it is a matter of degree, for people with ADHD these symptoms are much more severe and debilitating.

For example, take the losing your keys thing... sure a lot of people lose their keys sometimes. I have a family member with ADHD living in a cold climate where she had to wear gloves to get to school, and she loses a pair of gloves everyday. It got to the point where she was spending so much on gloves that it was having a huge impact on her life. She was trying all types of strategies to not lose the gloves, yet none were working and she would still lose them. Most people, if they lose a pair of gloves, would then be able to pay extra attention, and not lose another pair the very next day.


Look, I've had the same experiences since I was a child and everything I am saying believe it or not in a way is the beliefs I've developed thinking about my issues (a coping mechanism even).

>Being bored is a sign of lack of interest- being unable to focus anyways when it is boring but critically important, and you are choosing to try to focus on it but still can't would be a sign of ADHD.

I mean do you know how many people have trouble doing something like exercising despite realizing how important it is? People fail to execute control in this area and others like it despite it being literally life threatening.

Boredom, lack of interest, stimulation, focus, arousal are all related. One cannot expect someone to be focused for hours, every day on something one has no interest in, despite its seeming importance to an outside party, especially in regards to children. How do you expect a child to understand the importance of sitting quietly in class for 8 hours a day then going home and doing homework for a reward 20-25 years down the line that they can't comprehend? You're told it's important, but there is nothing within, nothing at the present or near future, that is enjoyable, fulfilling, in accomplishing these goals. Things are made far worse for example, if you as a child have social anxiety, and hate the school environment, and you drain most of your mental energy on just navigating socially, and come home hating your life.

Speaking of my experiences, truth is there is much I loved to do, could focus on for hours, and sure as shit could have excelled at. I loved reading history books on my own for example, walking around in circles and thinking about god and evolution, and writing bonkers political essays as kid. I loved video games, trouble shooting things, and making things which is how I got into programming. And absolutely none of my interests were reflected in school, which is the SOLE criteria where any outside person (and in turn, me) would judge me, my ability to focus on "what's important". And in turn all these interests largely faded away, having no backing or relevance to my real world, and all I was left with is feeling inadequate, useless, and angry as soon as I thought about the "important" things I had to do.

I still realized I knew I had to them yes, so I did the bare minimum the last minute, and it worked, so I kept doing the same. I've come to see that as a perfectly rational, functional thing to do. Now if I can't focus on something "important" like my job, I think "fuck it, it really is boring, let me see if there's something more interesting", and yay, it works.

There is a whole another class of kids which I don't imagine are reflected in the ADHD diagnosis, those that just said "fuck this" early on, didn't even care to try, and became troublemakers.

What I'd consider "critically important" executive function is things like are you able to run out your house in a fire, can you drive a car and turn left when you have to, not can you devote 8-10 hours of your life for 20 years to something you intrinsically don't want to do.

All this aside, your or my feelings about how difficult it was in relation to other people mean nothing. My criticism is, scientifically, how do you measure any of this, how do you even know what the baseline is? How do you factor things like how much someone actually wants to do something, anxiety, anger, risk tolerance, addictions etc that all come into effect when a person makes a decision to sit down and do work? How do you control for person's interests vs their environmental needs?

>This is absolute nonsense, it's like saying that getting an X-ray is harmful, because if people know their leg is broken, it might make them think they can't walk on it like normal.

Not a fan of analogies. You can recognize your defects without the label of adhd. Most of what you've said is the benefits of stimulants, a sense of community, and a sense of acceptance. An adhd diagnosis helps with all these of course as they're locked in behind the diagnosis. I didn't say it's not helpful, I said it can be harmful in some ways, or at least, I don't think its the most ideal solution.


Thanks for sharing. From your experience I suspect you have ADHD, which is why it seems to you like everyone experiences these things, when actually they don't.

People without ADHD are able to force themselves to do things they have no interest in, just because it needs to be done. I'm not saying doing that a lot is at good thing, or a recipe for a rewarding life... but the fact remains that our society is structured around rewarding and pressuring people to do things they have no interest in for advancement in school, careers, etc. My experience of school was that it was totally ignorant of the fact that some people have interests and like to learn things, and was based almost entirely on the idea of forcing behaviors with the threat of negative consequences - and for better or worse it was able to force most kids, but not the ones with ADHD.

Hyperfocusing on things you love is what you are describing in your second longer paragraph, and that is a key symptom of ADHD. In some instances it can be a huge advantage- I am a successful scientist because I hyperfocus on problems, and solve them. There are some real advantages to ADHD, along with many disadvantages, and ability to focus more deeply without distraction on things you are passionate about is a big advantage.

It's common for people with ADHD to just say "fuck it" and decide not to do what they are supposed to do, but then often feel guilty about it... not really realizing it was never a choice- they still wouldn't have been able to do it if they hadn't said "fuck it" but instead said "I'm going to just double down and do this even though I hate it." They can do the bare minimum at the last minute because the massive stress and anxiety at the last minute acts exactly like a stimulant, and suddenly gives them more executive control.

So how do you recognize ADHD scientifically? There is a pretty thorough system to clinically evaluate people that involves extensive question and answers about situations in your life, as well as interviews with multiple 3rd party people in your life. It's not perfect, but it's constantly being improved and is pretty good.

Sure, an ADHD diagnosis could have some disadvantages, but overall it is a very serious and very treatable condition where the treatment has well documented improved outcomes. ADHD has a shockingly high mortality rate, and treatment with medication causes a drastic reduction in mortality from unnatural causes like accidental injury and suicide.

I think you should check out the Hacking your ADHD podcast- https://www.hackingyouradhd.com/


I have an ADHD diagnosis. I think the diagnostic criteria is a joke (and I know at least 3-4 people who have gotten a diagnosis because they just wanted stimulants, so its not as hard as you might think), and having thought about all these things for a long time now I just have an entirely different interpretation. I used to 100% believe and push the ideas you are talking about so grant me the belief that I am not coming from a place of ignorance or hatred.

>People without ADHD are able to force themselves to do things they have no interest in, just because it needs to be done.

I don't think this is substantiated, or at least is far too simplistic. What do you consider needs to be "done"? As I said for example, to me this would mean life critical things, like you press on the brakes when you need to, you run out of fire when there is one, not you focus hours a day on something for a goal 20 years out because it will make your life a better one in the future. Thats not something I "need" to do, its something I wish I wanted just to avoid the consequences of being berated, feeling inadequate, etc. And if I found that I am able to get away with it doing things with the least possible effort, then that seems like a perfectly rational and functional thing for an animal to do. I tell ya, if I could go back, what I'd do is give far less of a fuck.

I think you have far more "executive control" than you think, I think its the narrow criteria, the one pressured by the existing societal/economic structure, you are evaluating against.

How many people have trouble exercising for example, despite knowing how important it is? People fail to control their urges when it comes to their eating habits, sexual urges, their emotions, addictions and all manner of things.

>My experience of school was that it was totally ignorant of the fact that some people have interests and like to learn things, and was based almost entirely on the idea of forcing behaviors with the threat of negative consequences - and for better or worse it was able to force most kids, but not the ones with ADHD.

I don't know about that. I'd say in a class of ~500 people, maybe 50-75 were actually all that focused on succeeding, and most of them were from well off with wealthy families and good homes. The bottom 100-200 didn't give a flying fuck, and ditched classes, smoked weed in school, cheated as much as they could. The average person Id say maybe cared somewhat, but wasn't all that motivated and did what they had to do to get by. I only felt like I had adhd because I felt that I cared more than the rest of the kids, but wasnt able to do my work. But what was required was so far off who I am as a person that looking back its unreasonable that Id be able to have. I mean it would literally make me angry thinking about stupid the assignments were, thats all I could think about trying to do them.

>Hyperfocusing on things you love is what you are describing in your second longer paragraph, and that is a key symptom of ADHD. In some instances it can be a huge advantage- I am a successful scientist because I hyperfocus on problems, and solve them. There are some real advantages to ADHD, along with many disadvantages, and ability to focus more deeply without distraction on things you are passionate about is a big advantage.

So imagine you were in a different environment that catered to your interests or style of learning. Now all of a sudden you're motivated, succeeding and everyone wants to be like you. Do you feel troubled, wanting to go to a psychiatrist to be diagnosed? Imagine you put all the "normal" people into an environment void of social interaction, non concrete assignments, and whatever other characteristics of normal school, and evaluated them and berated them on the tasks you're able to focus on. Do you think they'd just be able to adapt? And would failing to do so would grant them a diagnosis?

Another thing I found really surprising is that when I got my second job, all of a sudden I was insanely happy, motivated, focused at work and outside it. Then things changed again. I'd pretty sure Id get an ADHD diagnosis any year before that, but those two years? No way. I was more focused and motivated than now where I am taking 30mg of adderall every day. How could that be? The answer is a difference of a bunch of life factors, like the fact that my job now is boring as hell, I dont have much friends, Im not physically active as I used to, etc. These are all CRITICAL factors in focus, and its not something the diagnostic criteria is really even able to factor out.

Now, it does make complete sense that people's brain vary and some us are wired differently, with some people being more risk tolerant (and thus not caring as much about future consequences), some people needing more stimulation to feel motivated, etc. But IMO, what we consider ADHD is far more complicated than a lack of "executive control"


My apologies for assuming you were ignorant about ADHD. I agree what I was saying about focus is too simplistic, I was incorrectly thinking you weren't understanding even a simplified explanation of ADHD.

I think it's more accurate to say that the combination of factors that influence attention is different for people with ADHD, with a lot more emphasis on interest and less on other factors. When you say "its something I wish I wanted just to avoid the consequences of being berated, feeling inadequate, etc." - I think most people without ADHD are able to choose to do those things anyways if they decide it is a top priority, and put a lot of effort into it. I have chosen to do those things, tried to put in a lot of effort and energy, to no effect. That's not to say it's even a good idea to be able to do that, but it is a fundamental difference. I've wanted things a lot badder than other people, fought a lot harder for them, and been unable to do them, when I saw other people with very little interest or desire do them easily- and they were even less fundamentally capable of actually doing them, but able to consistently sit down and make progress.

I also agree that what is defined as a psychiatric disorder or disability depends on cultural context- but it's not cultural alone, it's an interaction between the natural variability between people, and the cultural context. Where someone is different mentally in a way they can't control, that causes them to suffer, within the context of a given cultures norms and expectations, that is the origin of all mental disorders. ADHD is a 'different' brain phenotype that isn't fundamentally worse- it also has some serious advantages, and I agree that in a culture where ADHD people were normal, non-ADHD people would be seen to be disabled. They would be seen to have a "flightly" and "shallow" attention that shifts from one thing to another on short intervals, and is too influenced by things like social demands, and not actual interest or passion. People with ADHD are also used to exerting a lot more mental effort to get things done, and build a stronger will as a result. For example, I have a hobby doing competitive strength competitions, and the mental effort I usually expend to get my work done, makes it really easy to push through physically painful and grueling training and competition that other people usually can't do. It's like I'm normally pushing against a wall all day long to no effect, but in this particular activity, I suddenly have no such wall and everything feels easy when it's hard for others.

Those lifestyle factors that influenced your focus, happiness, and motivation level are huge, and are useful tools for people with ADHD. However, there is a counter cultural narrative that those type of things shouldn't matter, and that you should just double down and do your work without worrying about things like that. This narrative might work for some people, but is especially a disaster for people with ADHD, but getting a diagnosis, and getting in a community of people that help each other find tools that work can be an antidote to that. Our culture has a lot of protestant work ethic values - that it is fundamentally morally superior to just do your expected duties, even if, especially if, you really don't want to do them.

I've also had times in my life where I was in a situation where I had a lot of focus and motivation, without any ADHD medication. But I see the effectiveness of these situations as exactly supporting the narrative of executive control dysfunction - if you engineer your environment and situation so less executive control is required to meet your goals, this is a powerful tool for managing ADHD. If you understand ADHD and what factors affect the level of executive control required, instead of happening on good periods in your life just by luck, you can create them consistently. That is, I think a more powerful (but not mutually exclusive) approach than even medication. Consistently having fun, playing, and adventuring in your work and life in general is a very effective ADHD management technique.

Would you summarize your view on ADHD as that it is just a mismatch between some subset of people, and protestant work ethic as a system for motivation? And that, since the protestant work ethic is fundamentally shitty, ADHD shouldn't be seen as a disability? I can agree with that somewhat, but it's of little help to a kid suffering in school. Moreover, I find ADHD treatment to make me better at things I do love. I want to be able to finish projects I start. I want to be able to notice when I'm in a sailboat race that a sail is trimmed wrong, and not hyperfocus on something else.


> I think it's more accurate to say that the combination of factors that influence attention is different for people with ADHD, with a lot more emphasis on interest and less on other factors. When you say "its something I wish I wanted just to avoid the consequences of being berated, feeling inadequate, etc." - I think most people without ADHD are able to choose to do those things anyways if they decide it is a top priority, and put a lot of effort into it. I have chosen to do those things, tried to put in a lot of effort and energy, to no effect. That's not to say it's even a good idea to be able to do that, but it is a fundamental difference. I've wanted things a lot badder than other people, fought a lot harder for them, and been unable to do them, when I saw other people with very little interest or desire do them easily- and they were even less fundamentally capable of actually doing them, but able to consistently sit down and make progress.

My question to you, what makes you so sure that your feelings are accurate about this? We know how we feel about something, we don't quite know what other people are going through. If were to talk about this as a science, its 100x more difficult to measure and quantify these things.

But let me point a few things out here.

1. I think most people are not hard working at all. Most people to me seem like they don't have much hobbies or interests in the first place, and don't try to get into something to begin with. Most people seem unable to stick with doing things they are interested in, like playing music or picking up a sport or etc. This is pretty evident if you been in a club, or taught a class or something. Most people will simply not stick with it and drop out. I think you're comparing yourself to a rather small subset of the population.

2. You said you're a scientist. This is above what most people achieve. Now I don't know when you got your diagnosis/treatment but I assume you did well enough up until that point that this was still a possibility for you. Same is true for me, I graduated college and am software engineer and I did really well in my field. Career aside, I've got pretty into skiing, rollerblading, dancing, playing keyboard, chess, got my pilots license, etc. Now I haven't really stuck with anything more than 6 months really, but I think this is more than most people. I didn't get diagnosed until last year.

My point here is, our feelings aside, we did pretty damn well and by all accounts are functional adults capable of doing many many many things. So where is the deficiency exactly? I'd venture to say your feeling is that you haven't accomplished as much as you believe you could have.

> Where someone is different mentally in a way they can't control, that causes them to suffer, within the context of a given cultures norms and expectations, that is the origin of all mental disorders. ADHD is a 'different' brain phenotype that isn't fundamentally worse- it also has some serious advantages, and I agree that in a culture where ADHD people were normal, non-ADHD people would be seen to be disabled

Glad we agree on this. A lot of people see it as simply being a defect, and attempt to attribute all their behaviors, shortcomings or otherwise, as being fundamentally tied to the diagnosis. I saw a popular thread on /r/adhd for example saying "Trouble with eye contact during sex, does anyone else have this?", with all the comments saying "omg, thats me too!". Even without a diagnosis, I think a lot of people (and this used to be me, which is why I know its true to some extent) will start to conceptualize their issues in terms of ADHD.

This is where I see it being harmful. Yes, as a matter of treatment, like I said I don't have much qualms. I don't even care if people take illegal drugs for stress relief, so I certainly don't care even if people wanted to take stimulants to make their job easier. My issues are with the science of it.

>But I see the effectiveness of these situations as exactly supporting the narrative of executive control dysfunction - if you engineer your environment and situation so less executive control is required to meet your goals, this is a powerful tool for managing ADHD. If you understand ADHD and what factors affect the level of executive control required, instead of happening on good periods in your life just by luck, you can create them consistently. That is, I think a more powerful (but not mutually exclusive) approach than even medication. Consistently having fun, playing, and adventuring in your work and life in general is a very effective ADHD management technique.

Well this is effective for everyone ain't it? Having friends, going out, trying something new once in a while, seeing progress in your relationships or interests or work or whatever. It was a wild time because I had been depressed all my years prior, and all of sudden it made sense why. How could I have expected to be happy sitting at home all day every day doing the same things over and over again?

>Would you summarize your view on ADHD as that it is just a mismatch between some subset of people, and protestant work ethic as a system for motivation? And that, since the protestant work ethic is fundamentally shitty, ADHD shouldn't be seen as a disability? I can agree with that somewhat, but it's of little help to a kid suffering in school. Moreover, I find ADHD treatment to make me better at things I do love. I want to be able to finish projects I start. I want to be able to notice when I'm in a sailboat race that a sail is trimmed wrong, and not hyperfocus on something else.

In part, yes. Because it doesn't matter if you functionally perfectly fine in all other aspects of your life, or even if you don't function in a ton of ways, its your ability to work and succeed in this environment that will determine how you feel about yourself and whether or not you go into a psychiatrists office. It doesn't matter if you could have been a chess grandmaster, or an author or another Alex Honnold, its primarily that you can't be happy being an obedient kid doing what you hate for 20 years that determines a diagnosis.

But my view first and foremost is that human behavior is extremely complicated, and short of physical evidence, trying to tie 10 different complex behaviors into a singular unknown cause is an entirely manufactured approach. I have a lot to say about this but it goes back to my initial comment.

Categorizing something doesn't add information. Nay, it takes out all the actual details and abstracts it into something that is easier to understand. If I talk about all my issues and a psychiatrist says "we call that ADHD", they haven't discovered something new that is true about me, they have just given it a label. And if we communicate through those labels, were working with less information, not more. Then we find facts that are you true about these generalizations, and then people take those facts and thinks it applies to them, because they're part of that label. Its so silly logically. Its like if a scientist was like "all these things with fur are Jababas.", "we studied all the Jababas and found eating leaves increases their mortality by 20%", and then thinking "its got fur, leaves are good for it" Hell thats better science since at least the attribution to the categorization is definite.

I personally find it so reductive of the human experience but that's beside my point.

>kid suffering in school

Imo, get rid of the prison-like school system. Get rid of the standardized testing and required certifications like a GED. Stop advocating for this singular path of school->(high paying field degree) college->job. Give more avenues for education, different learning styles, etc. I mean hell, for anyone who actually gives a shit its easy to see that a kid with social anxiety isn't going to do so well being in school with thousands of kids. Problem is no one gives a shit and our systems are so set in stone, its very difficult to change anything.


You're right I don't know what other people experience... it is a mystery to me why some many adults don't seem to do much. If I ask them they'll say they just don't want to- but why don't they want to? Apparently doing the same stuff is much harder for me, having ADHD, yet I do it and they don't- and I don't understand why they don't. That said, I know people that are as motivated and skilled as I am but don't have ADHD, and they are more successful than me- although in that case I am comparing myself to really a minuscule group of people. And almost none of them have kids or hobbies.

I have been very successful in my career, and it sound like you have also, but with an enormous amount of effort relative to the outcome. I have spent months stressed about getting work done and getting no work done. I had entire terms in undergrad where I did zero homework, and was nearly kicked out. It wasn't that I was slacking off, I was under enormous stress trying to do the thing, and not doing it.

I agree the label of ADHD isn't perfect, and groups a lot of potentially different things together- but it is the best we have been able to do so far, and it works. By grouping people together by a criteria we can develop treatments that apply to that group, study them, and use the ones that work best. Hopefully it will continue to evolve and improve.

As far as the school system- it was a living nightmare for me, and apparently for most people with ADHD, but I don't think most people feel that way. Most adults I talk to loved school, attend high school reunions, etc. There is no societal consensus that it sucks and needs to be fixed, no energy for the coordination that would be required. This might be another place where the ADHD label is useful - if we can prove that it sucks for people with ADHD, they will have pressure to fix it, or else be refusing to make it accessible for a disabled group.

You need to look at political and social realities to see where you can actually make things better for people with your effort, not how it should be ideally.


Your comment made me realize I totally do this. I at least frisk my pockets every time I stand.

I think thats andoando's point, people do things fairly unconsciously so symptoms which align them with a particular diagnosis can be absent for a multitude of reasons. In your case you developed an unconscious habit of frisking your pockets as part of developing a coping strategy. It may be coping with "ADHD" or coping with being a flawed human as we all are.

The symptoms tend to appear together, just like many datasets it is not some perfect line or cluster of symptoms that always appear together at the same time for everyone. Sure, maybe some statistical analysis will reveal that some symptoms should belong in the classification of adhd and others shouldn’t, but given the near infinite possible symptoms a person may exhibit, it’s interesting that there are a few that seem to appear often.

It’s not just ADHD. Consider OCD, while there are several sub types and triggers, many of the traits and rituals are very similar (repetitive washing, locking of doors, uncomfortably violent ideation) so much so that it’s clear they are related.

And if you’re a familiar of these people, you will experience their condition undoubtedly, when compared to a neurotypical.


Based on what data can you say these symptoms tend to come together though?

This is a whole another problem with the diagnosis. A human being is making subjective judgements based on the self reporting of another human being. Most of the dsm is stuff like "is often inattentive in conversations", "often misplaces things".

How often is "often"? How do you know on average how many times people misplace things?

I have no issues with this at all if we just admit its not really a science and were just trying to treat patients


It’s pretty easy to show that while on one scatter plot questionnaire results of depressed people may tend to form a cluster of points, typical medication is only working in half of the cases, ergo if we add one more dimension than we could separate it into at least two clusters with probably widely different physical explanation.

Behavioral biology is still a nascent field. Finding concrete biomarkers is the holy grail if diagnosis, but behavioral observation is the best we’ve got, and it so happens that certain traits tend to cluster, so the DSM and the like have resorted to shorthands. When biological mechanisms can be teased out, then we might see finer grained diagnoses and treatments.

This study would make a lot sense, that is why may studies in the area found that talk therapy in conjunction with medication are way more effective and less relapse than just medication along. Dr. Grof has done quite bit of work in that are.

Personalised brain circuit require personalised therapy, and talk therapy with well trained therapist seems to be the key to treat the cause instead of symptom. All the difrerent fancy medications are "throw stuff against the wall and see what works".


I, for one, would be interested in hearing more about your experience. How did you choose a clinic? How much did it cost? How many sessions did you do? Were there any negative effects?

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...


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


Pairs of nodes, I believe. The connectivity is usually an edge weight between the ROI "nodes," the graph points.

Yes, but how did they define their nodes? The authors used maps from neurosynth, which are voxel-wise. They could be using voxels as nodes, but it seems unlikely to me.

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


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.

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.

I'm immediately put in mind of the double empathy paper: 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.


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.

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!


You might enjoy this book [1] which dives into the questions you are asking.

[1] https://lisafeldmanbarrett.com/books/how-emotions-are-made/


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


Either is sufficient for a diagnosis, I'd imagine, since you're looking at two sides of the same coin.

Both could help for a diagnosis, but the first one also helps with finding treatments, the second one doesn't.

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.


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.


Consider patients that present with general malaise, fatigue, lack of motivation, grumpiness, etc.

Without therapy to teach them to interrogate their thoughts to determine if they have negative feedback cycles, how nice would it be to just say "Oh we detect that you are a ruminator, you should do CBT and we'll prop you up with some SSRI in the meantime." The same way we'd just do a Vitamin D or Iron deficiency check.


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.


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" ?

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.


IIRC it was found that the anti-inflammatory effects of SSRIs are partially responsible for their benefits

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.

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.


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.


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


I don't think defunding studies on mental illness to fund those who suffer with it is the way to get progress on helping. You're entirely right to be unimpressed with this study and to feel some despair that essentially no study that comes out today will materially affect your life.

But nevertheless, if these studies don't happen, there will forever be people who have to suffer like you do.

Instead, there are many other places where money is being wasted on things that not only have 0 chance of helping, but are actively hurting people. The war budget is many times over all of the psychiatric research money ever spent - maybe we should target taking money from there to help people people struggling with mental illness or homelessness or both, before taking that money from research.


So, I agree that an awful lot of what passes for research and treatment is chosen based on the comfort zone of the practitioners, more than what is most likely to be found to help the patient. But I think in this case you are attacking one of the ones that is more likely to be useful.

> 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).


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.


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.


> 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.


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...


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-disruption...

So I feel you are confusing mental health and mental illness and confusing compassion with a profit making operation.


> 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 ?


> 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.


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.


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.


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?


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.


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"




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