[nth_order]

Yeah, but thats hardly news, we have known that for decades. Otherwise direct serotonin releasers would be the most useful ADs. But these mostly give people nausea and serotonin syndrome. ADs work mostly by being FIASMAs, reducing inflammation and oxidative stress, increasing neurogenesis and neuroplasticity, increasing the activity of other monoaminergic systems, and the serotonergic portion is mostly explained by downregulation of 5-HT1A autoreceptors due to chronicly high extrasynaptic 5-HT levels. This also explains the delayed action of ADs.

At least this is my knowledge from when I last researched this topic in depth.

But that would be a little bit too much for the general public, so it is simplified, to this annoying effect that everyone talks of "low serotonin levels" where in fact the underlying systems are way more complex.

[moth-fuzz]

I have a friend that's convinced that her ADHD 'causes depression' because her brain does not produce 'enough dopamine'. I'm noticing more and more among my peers a mythology around brain chemicals that's about as accurate as the four humors but with a scientific-sounding veneer. All brain function (and thus all bodily function, because the brain is the whole person /s) can be traced back to the presence or absence of a nominal amount of certain chemicals.

I wonder how the popular understanding of these processes will evolve as more and more is discovered and understood.

[hirvi74]

> I have a friend that's convinced that her ADHD 'causes depression' because her brain does not produce 'enough dopamine'

Interesting, and she is somewhat right, but is wrong about the 'enough dopamine' part, if I understand correctly. I have heard that dopamine plays a role in ADHD (seems likely our neurotransmitters don't absorb enough, but even that is an overly simplistic explanation of the unknown and true reality).

But yea, I also have ADHD and yes, it can cause depression. Not due to dopamine, but because of the negative feedback-loop ADHD can create.

For example, let's pretend I have some big assignment I need to complete, and I am without access treatment (professional or self-medication). If can't muster the "powers" to work on/finish said assignment, I start to get extremely anxious and/or I get depressed that I failed to finish said assignment. Said anxiety/depression only makes my ADHD symptoms worse which makes the anxiety/depression worse. Thus I will struggle more to complete future work, which only fuels said anxiety/depression even more, and the loop keeps on iterating.

Though, sometimes the anxiety can be extremely helpful. I can muster some insane kind of hyperfocus due to the pressure of a looming deadline. I spent decades of my life relying on anxiety to complete tasks, that even with treatment, it's extremely hard to start and finish tasks without the anxiety.

It's an annoying and rough way to live, but oh well, I am just grateful I do not have something worse.

[kemiller]

I think ADHD causes depression because you get constant negative feedback from (many) teachers & bosses.

[wongarsu]

I think a lot of this is about English (and probably most languages) being vary lacking in ways to describe both short-time and long-time mood effects. Talking about a dopamine rush from completing a difficult task or an endorphin rush from sport isn't very accurate, but despite everyone knowing the feeling we never made better words for them.

Similarly "I've low dopamine" is just a modern version of "I have the blues" or "I'm depressed". That's all good, as long as everyone involved knows that it's a short hand, or maybe a double-meaning of the word, not an actual medical description. Just like somebody who is "a little OCD" has none of the symptoms of actual OCD.

[eurasiantiger]

It’s more like she has quantitatively or qualitatively different dopamine receptors.

[jugg1es]

This is like the right/left brain generalization that everyone seems to still believe in.

[oasisbob]

The low-dopamine hypothesis for ADHD is a legitimate idea still being actively studied.

[ZeroGravitas]

And now the opposite happens with headlines that imply "your medication is suddenly revealed to be useless" when in fact we've been aware that we don't know how it works for a while, but we're still reasonably sure it helps, which perhaps explains the increase in prescription more than the "serotonin is the only thing that matters" theory which the experts ruled out a while ago.

[virtuallynathan]

They barely work better than placebo, from what I saw in my reading of the literature.

[harborseal]

Yes, but people are still being told by their psychiatrists that depression is caused by low serotonin levels as if it were an objective fact. Seeing this happen made me lose a lot of trust in the medical profession. Is it like this for all illnesses or just mental ones?

[kmmlng]

I don't think it is an isolated incident. Once something has become "known" among the public and the medical profession, it seems quite difficult to update it. Another example is the dietary cholesterol issue.

The human body is incredibly complex and we have quite limited tools to study it, so we are bound to arrive at wrong conclusions. That by itself is to be expected, but what does really worry me is this missing knowledge updating mechanism. It can take decades for quite a substantial update on what we thought we knew to trickle down from academia to practicing medical professionals.

At this point, if you have any kind of scientific literacy, it might be a good idea to verify whatever your doctor claims.

[hirvi74]

I was told by a psychiatrist that I respect that one day in the future we may look back on psychiatry of today like we look at blood-letting and lobotomies of the past.

[kerryoco]

many illnesses are reproducible. you can give people viruses and they do indeed get sick. so i don't think you need to discount the entirety of medicine.

afaik, there is no reproducible causality for depression; we can't induce it. we only measure it's correlations and have % confidence in hypotheses.

[Workaccount2]

Anytime I learn about bodily functions I become more and more aware of how shit it's engineering is. Works amazing, sure, but try and fix or debug anything? Good luck.

[hutzlibu]

Erm, are you aware of any other machine, that is able for self repairing and self replicating in a complex and changing environment?

I really would not call my body bad engineering, just because I do not understand how it works in detail.

Rather the opposite, the more I learn, the more amazed I am, how awesome it all is. The complex interactions of chemical, electrical and physical components. (And who knows, maybe even quantum field elements.)

I could not design anything remotely complex at all.

Also, I debug and fix my body all the time, or rather, my body does this mostly in auto mode.

[rustybelt]

Are you saying God likes to yeet buggy unmaintainable spaghetti code directly into production?

[o_nate]

I guess we should be grateful our brains are complex enough to understand anything. Maybe it's too much to ask to ask them to be able to understand themselves. They would need to get more complex to understand themselves, but then that complexity would make them more difficult to understand. It's the snake trying to swallow its own tail.

[_jal]

Tractors don't know how to repair each other, either.

[onefuncman]

almost like life is an MVP that could pivot at any time

[barbs]

How common is seretonin syndrome amongst people who take SSRIs?

My understanding of seretonin syndrome is that it's a serious life-threatening condition that can occasionally occur when people take too much MDMA.

[lighttower]

Can you point us to a source for the accepted real physiological effects of ADs that you shared above?

[nth_order]

Sure - I should have given some sources in my original comment. The order of my list of purported mechanisms is also not really ordered by significance. I think generally, more and more mechanisms of AD efficacy are discovered, and it can seem that the more we know, the less we know. Additionally of course, there are like 15 different classes of ADs, with hundreds of different compounds in total. What we know for sure I think is that the serotonin and also the monoamine hypotheses of depression are highly oversimplified and even internally contradictory, and many more targets and way more general biochemical mechanisms in the brain must be involved in depression.

But anyways, here are some pointers:

- Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/)

- Wikipedia: Biology of Depression (https://en.wikipedia.org/wiki/Biology_of_depression#Monoamin...) has some good sources

- One source covering the 5-HT1A autoreceptor downregulation part in particular there is "Serotonin autoreceptor function and antidepressant drug action" (https://pubmed.ncbi.nlm.nih.gov/10890313/)

- This is also covered in "Mechanisms underlying the speed of onset of antidepressant response": https://link.springer.com/chapter/10.1007/978-3-0348-8344-3_...

- I personally like the books "Antidepressants" by Leonard (that the previous paper is a chapter of) and "Anxiolytics" by Briley and Nutt. These discuss really a wealth of observed/purported mechanisms, also for example including the significance of late gene products.

- Wikipedia: Pharmacology of antidepressants (https://en.wikipedia.org/wiki/Pharmacology_of_antidepressant...) has great sources, especially on the anti-inflammatory and immunomodulative pathways, and introducing HPA axis modulation as another possible pathway.

- Here's something about the significance of common ADs being FIASMAs: https://www.semanticscholar.org/paper/High-activity-of-acid-... - also check out the related articles below for more interesting material.

- ADs and neuroplasticity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/

- ADs and neurogenesis (this is not clear-cut in its clinical significance, and many ordinary things like exercise can promote neurogenesis): https://www.sciencedirect.com/science/article/abs/pii/S01637... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155214/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230505/