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by bbor 593 days ago
Great convo, love all the details on both sides! There's shockingly little long-term study of executive dysfunction because it's so new, so I understand your dubiousness. I never read that before about neurotransmitter reuptake, but it seems plausible -- it's really hard to say. My fave AD(H)D site (low bar...) quotes a doctor saying (in 2024);

  ADHD was the first disorder found to be the result of a deficiency of a specific neurotransmitter — in this case, norepinephrine — and the first disorder found to respond to medications to correct this underlying deficiency. 
- https://www.additudemag.com/adhd-neuroscience-101/

But then a basic search on the actual lit paints a much murkier picture:

  We found no significant differences in NET availability or regional distribution between patients with ADHD and healthy controls in all investigated brain regions (F1,41 < 0.01; P = .96). Furthermore, we identified no significant association between ADHD symptom severity and regional NET availability.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4699255/

Which is a synechdoche of the broader dynamics around the disease IMO; lots of confident people with degrees saying stuff, often while trying to sell you services or medications, but the lit is still mostly vague. The only solid finding I know about ADHD is that it lowers life expectancy... TL;DR: I wouldn't personally be so confident it's about reuptake rather than production.

To give my hot science take, I think this is a somewhat inevitable result of our differential-diagnosis-based psychiatry system. ADHD is, objectively speaking, a set of symptoms. Common sense tells us that there's some common causes in the population, sure, but treating it as a causal condition rather than a opaque descriptor leads to a lot of confusion and heartache, IMHO. Such as;

  Sure, depression-induced anhedonia can result in executive dysfunction, but depression's not what ADHD is (even though ADHD can easily cause depression).
I don't have an issue with any of these specifics per-se, and I'm sure you're accurately describing your life (and mine, tbh!), but I don't believe this level of ontological separation is helpful in the longterm. Some people with depression and ADHD might have a completely different cause than people with one of either, or even than other people with both. This is why I like the 'software debugging' metaphor; it's easier to iteratively try improvements to an opaque system than it is to find the "true" cause or "real" solution. E.g.:

  So far I haven't seen evidence for myself that trying harder helps. Sometimes things happen (things like trauma) that manage to keep me motivated and functional for a while, but I haven't found a working strategy to manufacture this motivation at will yet.
You're not broken for being imperfect, you're just human - I would encourage you not to let this dissuade you from pushing yourself! I consider failure-to-motivate as a cognitive event in a system with a million inputs, not a subconscious choice you made because you're broken/sinful/lazy.

In those terms, I agree with your interlocutor; regular moderate exercise can really only help, in 99% of cases. It doesn't have to fix to help :)

1 comments

> lots of confident people with degrees saying stuff

This seems to be the case for so many diagnoses, ugh. I often feel like I have more paws-on experience with certain things than a lot of professionals out there, but I don't know if I'll ever really get to be an authority on any of this stuff, which is kind of a shame, in my opinion. I wish I could contribute what I know.

Some disorders are particularly often misunderstood which always feels a bit sad to me. Would one normally write a book in this situation?

> I wouldn't personally be so confident it's about reuptake rather than production.

I'm not necessarily as confident that it's definitely about reuptake as I am just not exactly convinced that it's definitely about production, if that makes any sense. Mostly because I personally have a case that I suspect of being about reuptake, even though I don't really have a way to verify that for sure. (I may never.)

If inhibiting reuptake has the same or a similar enough effect as increasing production, how is one to tell the difference? Many stimulants (like the amphetamines) act as releasing agents at the same time anyway; I happen to best like (and currently use) dexedrine, which happens to also be a dopamine releasing agent and not just a reuptake inhibitor. This fun fact naturally leads to "Hmm how exactly am I supposed to know for sure which mechanism of action is actually the one helping me the most". Or of course the possibility of "both is good, I could use both".

Thing is, we just really don't know right now and I'm not sure of any way to become any more certain about this myself. I definitely think this deserves to be an active area of research (there are many things I'd love to be active areas of research), but I don't know of anything ongoing at the moment. You never know though exactly what research may be ongoing, a paper could appear at any moment about this exact topic, but I'm not aware of any right now.

I will say though that in my opinion, I think the ongoing research into psilocybin could potentially turn out to be quite insightful and possibly relevant, because in my experience, serotonergic psychedelics temporarily disappear my ADHD, and they're also sorta almost a kind of stimulant (or at least LSD certainly is), so... close enough? Maybe not exactly close enough, but it's certainly some of the most exciting drug/brain research that I've seen in years. Here is which paper grabbed my attention and got me so excited about this: https://pmc.ncbi.nlm.nih.gov/articles/PMC11291293/

> I don't believe this level of ontological separation is helpful in the longterm. Some people with depression and ADHD might have a completely different cause than people with one of either, or even than other people with both.

Yes, of course. I don't mean to suggest that these diagnoses do a perfect (or even good enough in many cases) job of identifying root causes, because all they really are is those sets of symptoms that satisfy certain diagnostic criteria. So I therefore also don't mean to suggest that everybody with ADHD has the exact same root cause that I do, because it's currently impossible to test for that. (It's even hard to test for equivalence between two people, because we don't even know the objective difference between a lower level of dopamine in an otherwise normal brain and a higher level of dopamine reuptake in an otherwise normal brain, so we wouldn't know what to test equivalence with.)

It's hard enough just for me to find someone who's autistic in the same exact way that I am, let alone someone who also happens to match up with any of my other differences. (I think so far I've only found two other such people in total.) I just mean to say that I've never seen ADHD be caused by anhedonia, but I have seen and heard of many other things that could be confused for something like that. (It's really easy to confuse these things, which is probably why you say this level of separation isn't helpful.)

> you're just human

I get what you mean (that nobody's perfect), but I am otherkin, so please don't specifically call me human! (I should probably add this to my HN profile to be honest - not that people usually read profiles before they comment, but still)

> I would encourage you not to let this dissuade you from pushing yourself!

It doesn't entirely. I just can't always count on the push working because of how frequently it just doesn't. I can't recall how many times that I've fully, definitely decided to do something, turned to get up, and then just frozen in place. I had literally already fully decided to do the thing and was fully committed and my brain just suddenly said No. I literally freeze until I give up. The body simply refuses to move for that purpose in particular.

I have a hypothesis that this ability for the body to "disagree" with me could have been a contributing factor to my huge separation between mind and body, but I also have Dissociative Identity Disorder... so dissociation in all things, even between thoughts, is pretty normal for me at this point.