(Trying out cross-posting an answer I wrote on Quora to this blog.)
This is a very long and complicated story, and the science is at a rudimentary stage. I think the best thing you can do is read Siddhartha Mukherjee’s masterful piece on depression in the New York Times:
The Science and History of Treating Depression
Here’s a highly simplified take on some implications of this article (a must-read!) combined with some of the academic literature I have surveyed:
Some forms of depression may be equivalent to an inability to discover, create and/or access new possibilities in life. So if one gets stuck in a rut of apathy, ennui and/or sadness, one cannot feel motivated to try out or seek alternative behaviors, thoughts, and goals.
The hippocampus region of the brain may be crucial to the ability to recognize new contexts and situations. A region that is part of the hippocampal circuit — the dentate gyrus — is one of the only parts of the adult brain that produces new neurons, and this ability may be related to the brain’s ability to recognize new situations and opportunities.
There is some evidence that in depressed patients this ability to produce new neurons has been weakened. Electrical stimulation of the brain sometimes helps depressed patients, and this may be because neurogenesis in the dentate gyrus has been restored, at least partially. Chemical treatments such as SSRIs work in some cases, but this too appears to be related to the process of generating new neurons, rather than a chemical imbalance per se.
In other words, serotonin-based treatments, and deep brain stimulation may both assist the hippocampal circuit in its job of recognizing new contexts and opportunities.
And perhaps talk therapies and cognitive behavioral therapy also work to rejuvenate the brain’s ability to recognize and value new opportunities and goal-oriented behavior. But far more work is needed before all this can be considered solid science.