[carabiner]

I think for some forms of treatment-resistant depression, no "rapid" treatment can work because the depression has caused physical atrophy, mostly in the hippocampus, over many years. Various studies have shown this atrophy, both in MRI and cadaver studies. So the tissue loss might take years to recover unless we discover some new neurogenic compound (RIP NSI-189). Ketamine, SAINT TMS might still work for other depression though.

[willy_k]

The brain doesn’t necessarily need the same exact hardware to do the same function, but in adults if it’s lost they will probably not regain the function without intervention. Neuroplasticity-inducing substances may very well enable the brain to create new connections and rebuild functionality even if the physical neuronal mass does not recover.

This paper suggests as much: “Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects.”

https://www.nature.com/articles/s41467-022-30386-5