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I'm starting to pick off sub-topics from this omnibus question, which I think it's too broad to answer properly/directly in the SE format.

So, let's start with one of the claims there:

Lowering people's serotonin levels does not change their mood.

What do we know, experimentally, about the effect(s) on mood of lowering serotonin in humans? And (yeah) although asking too many questions in one is a bad idea, in this case we would have to consider at least three scenarios to get a decent picture (because depression, for instance, is known to have a genetic/heritable vulnerability/component):

  • lowering serotonin in otherwise healthy volunteers, with no history of depression
  • lowering serotonin in subjects with a history of depression
  • lowering serotonin in SSRI (or similarly) medicated patients

Potentially, we could try to matrix the type of subjects with the type of intervention, although at the moment I can recall only one intervention that could (ethically) be used: depletion of tryptophan (which is serotonin precursor) via competition from other amino acids. (Selective) neurotoxins, which are used in some animal studies, being a rather obvious no-no in live human subjects.

And to the extent that one can address this concisely (if not perhaps suggest/ask a different question), what are the methodological limitations of such experiments? One that I can think of is that since antidepressants need a bit of time to build up their effects to clinically detectable mood changes, perhaps the same time-related issue holds in the opposite direction, i.e. how long serotonin depletion lasts potentially could matter for the mood outcome of such experiments.

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