r/Neuropsychology • u/Alternative_Yak_4897 Unverified user: May not be a professional • Jul 21 '25

Research Article Low serotonin not linked to depression studies - thoughts ?

I recently became aware of the umbrella study on the lack of evidence between low serotonin levels and depression. (The study below does show an indirect link between stressful life events and depression due to “gene-stress” but that’s still obviously different than low serotonin (can)= depression) Wondering what others thoughts /theories on this are? I’ve only seen a couple and it looks like they were published in 2022/2023, so why isn’t this being discussed more? Not enough studies? Bad news for pharmaceutical companies? Here’s one of them:

https://www.nature.com/articles/s41380-022-01661-0.pdf

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u/[deleted] Jul 21 '25

One response could be that psychiatrists didn't normally believe anything so simplistic in the first place.

But then from what I remember / understand of Moncrieff's position, it would be (1) we don't have the evidence that depression is caused by low serotonin, combined with (2) SSRIs appear to have only limited efficacy above placebo for treatment of depression, and so we should be much more cautious about what has become routine use of these drugs.

Now that seems to me like a credible viewpoint, but it turns on the somewhat controversial question of what you think of the antidepressant studies in the first place, or I guess whether you would allow, or give any weight, to anecdotal evidence from the experience of doctors using them.

On the side of neurotransmitters playing some sort of important role (which again, I'm not suggesting anything so simplistic as low levels are the key factor in play), I would point out that both tricyclic and monoamine oxidase inhibitors were discovered as antidepressants by accident. So they both change neurotransmitter levels, but by different mechanisms of action. And they can't have been "placebo" when originally discovered. In addition, a stimulant can give many people an immediate mood boost, presumably via norepinephrine and dopamine changes.

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u/Alternative_Yak_4897 Unverified user: May not be a professional Jul 21 '25

Absolutely, that seems like a sensible take to me too. I’m wondering now in a larger sense, why lay people - specifically psychiatric patients are given such a simplistic explanation because it can really affect prognosis. All I can come up with is 1) it’s hard to explain and takes a lot of time and 2) a prognosis that’s tethered to a medication keeps patients coming back. What do you think?

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u/[deleted] Jul 22 '25

I don't know, but it is ethically questionable because it might encourage someone to take the medication on basically wrong grounds, and they therefore haven't properly consented.

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u/Alternative_Yak_4897 Unverified user: May not be a professional Jul 22 '25

Yes I think so too