Sapolsky on chronic stress and hippocampal damage:
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/

Chronic stress causes prolonged Cortisol release from the adrenals, which in turn feeds back to the hypothalamus and has a negative feedback on the cortisol release, as one would expect. However, there is more to this than a simple negative feedback loop. The hippocampus seems to have a negative influence upon the hypothalamic release of CRH, in turn lowering cortisol levels. Unfortunately, the sustained levels of cortisol, if an organism is chronically stressed, seem to inhibit the hippocampus through 3 possible mecahnisms described by sapolsky:
1)Temporary (reversible) retraction of hippocampal dendritic connections
2)Ihnibition of neurogenesis in the hippocampus
3)Hippocampal neurotoxicity = a loss of preexisting hippocampal neurons

This explains the loss of hippocampal volume that is common in severly depressed patients that express high cortisol levels, and might explain the permanency of various functional/mood/ learning losses as a result of depression working through permanent hippocampal damage.




The potentially good news is that anti depressants (Tianeptine - and SSRE [enhancer]) - and possibly other (SSRI's) [despite the seeming incongruity] increase BDNF, which in turn inhibits the effect of cortisol upon the hippocampus thereby preserving its integrity.
"Although the best known of these are the specific serotonin reuptake inhibitors such as Prozac, other efficacious drugs also block the reuptake of norepinephrine and/or dopamine. Nicely commensurate with the involvement of serotonin, there is some evidence that increased serotonin availability can stimulate cell proliferation in the hippocampus However, tianeptine is a distinctly atypical antidepressant (with, reputedly, only limited clinical efficacy), which increases serotonin reuptake. Thus, it decreases synaptic serotonin concentrations, rather than enhancing them."



It may well be then, that antidepressants not only help the patient now, but if they can both lower stress now, and lower the deleterious effects of stress upon the hippocampus, that the patient is less likely to have lasting permanent damage to the hippocampus, and with it permanent damage to learning and mood centres!

It is worth mentioning that a few still think some sort of neurogenesis issue in the hippocampus could lead to depression, not the other way around, but they are a minority and evidence appears scarce.

I will leave you with the great man's words himself:
"Obviously, more research is needed. It would be a boon to biological psychiatry if any antidepressants can prevent some of the neurobiological correlates of depression, in addition to alleviating the affective symptoms. But findings such as these also support the frequent uphill battle for those who study depression, or suffer from it, namely convincing others that this is a real biological disorder, rather than some sort of failure of fortitude or spirit."