"At its very worst, this reality cultivates a sort of “who cares?” mentality in psychiatrists when it comes to neurobiology"
I am a current PGY4 and this is approach I take. Medicine is full of bio-plausibility that turns out to be wrong. In the end, we need to rely on clinical studies and results. Perhaps things are changing, but as of yet, I don't think we have models accurate to be worth clinically interesting. However, I'm happy for researchers to care about this more than I do.
I've enjoyed the Substack posts you've written so far, look forward to reading more.
> Subjectively, this is exactly matches my experience with my prescribed stimulants. I just seem to be able to “tune out” distractions better. It also explains a sort of cognitive rigidity that I’ve noticed while on stimulants. For example, when I play chess while not on stimulants, my focus is so poor that I just can’t compute more than 2-3 moves ahead and I will often forget the last line I calculated. Stimulants improve my ability to calculate, but I consider alternative lines much less frequently and find myself returning repeatedly to the one or two lines that I originally fixated on.6
>
> It’s the same with video games - I actually seem to perform worse on stimulants in games that require me to constantly check up on multiple different systems or adjust my strategy on the fly.
This is sort of rigid thinking is because traditional ADHD stimulants being releasers and reuptake inhibitors are very D1 heavy (likely just because D1 is the most abundantly expressed dopamine receptor in the brain). D2 heavy drugs also behave as psychostimulants with a different cognitive profile that can produce quite different results.
I once got brain zaps from SNRI withdrawal and my first thought was not "how do I make this stop" but "what does this tell me about the role of serotonin in predictive coding".
Great presentation and discussion of the paper and relevance to PP. Wish it had been early enough in the day to have enjoyed a beer while I enjoyed this journal club.
Made me wonder how these findings could be extended in a couple of ways. One in terms of basic research would be 2P imaging in animal models (starting with mice). Other with functional imaging in humans.
Also found your first few paragraphs very interesting, ie how much does a psychiatrist think about Neurobiology when sitting in front of a patient. Took me back 40 years ago to when I did my first post doc. I was one of the "rat guys" in a Lab at NIMH that was predominantly clinical. So virtually all the seminars where biologically oriented, back then lot of talk of biomarkers, etc. But when I would hear discussions by the clinical folks (primarily psychiatrists) didn't hear much that was of biological mention. And of course when one of us rat folks would present at seminar, clinical folks would pay attention and ask good questions, but it was pretty obvious that there was a pretty wide gulf between what we were doing and what was being thought about in clinic. Hope that gulf can be closed some day.
Also found your opening paragraphs quite interesting.
Funny you should mention that - I was just at a small research day with both the clinical and neurosciences people and the disconnect is still very real.
Some sincere questions from the basic sciences folks that were honestly baffled as to why we're not using things like neuroimaging for diagnosis; they clearly didn't realize how little clinical utility they have at present.
From the other side, most of the clinicians were like "oh this is cool," but obviously didn't think it would be even remotely relevant to clinical work anytime soon.
here you go again, ruining my "low dopamine morning" (I'm catatonic)
"At its very worst, this reality cultivates a sort of “who cares?” mentality in psychiatrists when it comes to neurobiology"
I am a current PGY4 and this is approach I take. Medicine is full of bio-plausibility that turns out to be wrong. In the end, we need to rely on clinical studies and results. Perhaps things are changing, but as of yet, I don't think we have models accurate to be worth clinically interesting. However, I'm happy for researchers to care about this more than I do.
I've enjoyed the Substack posts you've written so far, look forward to reading more.
> Subjectively, this is exactly matches my experience with my prescribed stimulants. I just seem to be able to “tune out” distractions better. It also explains a sort of cognitive rigidity that I’ve noticed while on stimulants. For example, when I play chess while not on stimulants, my focus is so poor that I just can’t compute more than 2-3 moves ahead and I will often forget the last line I calculated. Stimulants improve my ability to calculate, but I consider alternative lines much less frequently and find myself returning repeatedly to the one or two lines that I originally fixated on.6
>
> It’s the same with video games - I actually seem to perform worse on stimulants in games that require me to constantly check up on multiple different systems or adjust my strategy on the fly.
This is sort of rigid thinking is because traditional ADHD stimulants being releasers and reuptake inhibitors are very D1 heavy (likely just because D1 is the most abundantly expressed dopamine receptor in the brain). D2 heavy drugs also behave as psychostimulants with a different cognitive profile that can produce quite different results.
I once got brain zaps from SNRI withdrawal and my first thought was not "how do I make this stop" but "what does this tell me about the role of serotonin in predictive coding".
Anyway, that's just an anecdote, but for those interest in the subject - my favorite paper in the world is this one by Matt Larkum - http://behavioralhealth2000.com/wp-content/uploads/2017/06/A-cellular-mechanism-for-cortical-associations-an-organizing-principle-for-the-cerebral-cortex.pdf - it explains how individual pyramidal cells make predictive coding work.
Great presentation and discussion of the paper and relevance to PP. Wish it had been early enough in the day to have enjoyed a beer while I enjoyed this journal club.
Made me wonder how these findings could be extended in a couple of ways. One in terms of basic research would be 2P imaging in animal models (starting with mice). Other with functional imaging in humans.
Also found your first few paragraphs very interesting, ie how much does a psychiatrist think about Neurobiology when sitting in front of a patient. Took me back 40 years ago to when I did my first post doc. I was one of the "rat guys" in a Lab at NIMH that was predominantly clinical. So virtually all the seminars where biologically oriented, back then lot of talk of biomarkers, etc. But when I would hear discussions by the clinical folks (primarily psychiatrists) didn't hear much that was of biological mention. And of course when one of us rat folks would present at seminar, clinical folks would pay attention and ask good questions, but it was pretty obvious that there was a pretty wide gulf between what we were doing and what was being thought about in clinic. Hope that gulf can be closed some day.
Also found your opening paragraphs quite interesting.
Funny you should mention that - I was just at a small research day with both the clinical and neurosciences people and the disconnect is still very real.
Some sincere questions from the basic sciences folks that were honestly baffled as to why we're not using things like neuroimaging for diagnosis; they clearly didn't realize how little clinical utility they have at present.
From the other side, most of the clinicians were like "oh this is cool," but obviously didn't think it would be even remotely relevant to clinical work anytime soon.
Looks like the back-half of this comment got cut off. I have thoughts, but would want to see your full thoughts before I respond