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Now you got me thinking about the idea of "gut brain" depression just like our normal brains can get depression...

An interesting thing to think about, science isn’t really sure why SSRIs work the way they do on depression [0]. The effect of the SSRI on brain serotonin is immediate, but the drugs take 3-4 weeks to actually have an effect on depressive symptoms.

There is a suspicion that SSRIs may change the gut microbiome, and that’s why it has an effect and why there is a time delay.

[0] https://www.discovermagazine.com/health/how-antidepressants-...

Are there any other credible hypotheses for why SSRIs take weeks to affect mood according to the literature, when their effect on the serotonin is immediate?

Yes, another is that they cause an increase in BDNF in the hippocampus, which stimulates neurogenesis there. This process of literally growing neurons takes weeks, even months.

Actually SSRIs usually have an immediate worsening effect, which then gradually resolves by week 3-4.

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