As a patient (and, at that, one who has been through many antidepressants that either did not work or made things profoundly worse), this is a simplistic view. The issue with antidepressants is that if they work, you can only expect them to make things more bearable. To allow you to do the hard psychological work on your own, now that you have the energy. Even if that energy comes with more anxiety and other strange effects on your psyche. But to say they are no more effective than placebo, based on a review of studies, is a typical professionals' response (no offense).
They DO work. Just not very well. And you have to go through the merry-go-round to find one that makes the grade, but once you find it, you hold onto it like a drowning man holds on to a lifebuoy.
I disagree with 'turning off' the mechanisms for depression but it's too complicated to discuss and I suppose you have a point. Thank you for mentioning ketamine and TMS, two treatments that need more research/sincere attention. (ECT.... not so much).
Finding the genes for depression? Pot of gold at the end of a rainbow. You may find a few genes that produce more innervation/receptor density in certain parts of the brain, but even then, the interaction between that and the emotions, the life experiences, is too complicated to imagine. And switching those genes off will come with some unpredictable consequences.
Actually (I'm almost done don't worry), that way of thinking frustrates me as a patient rather than a doctor. You always seem to be looking for the magic bullet. You will never find it. Alleviation - to a large degree, sure - is the best that can be hoped for. It is the search for the perfect way to fix X problem, especially mental illness, that leads to drugs created from incomplete information but based on a wonderful new idea, and therefore TD, anorgasmia and 'brain zaps', permanent sexual dysfunction from something like Propecia (and SSRIs but that's more controversial), etc. It is a trend amongst doctors and it has created a lot of problems and never a cure. Anyway.
To the other two responses, I have some issues with the NA/SE proposition. Consider MAOIs, especially selegiline ('EMSAM' which unfortunately we do not have here in Aus); bupropion, and the recent interest in triple reuptake inhibitors. Dopamine is a large factor in depression and it has unfortunately been overlooked. It doesn't have the same broad effect of SE or NE but it is still an important neurotransmitter involved in the enjoyment of everyday life.