'As discussed, the hippocampus plays a key role in declarative memory. As will become quite pertinent when we turn to depression, glucocorticoid exposure can impair LTP in the hippocampus and can even cause atrophy of neurons there. This phenomenon constitutes the opposite of the stress response in the amygdala. Severe stress can harm the hippocampus, preventing the consolidation of a conscious, explicit memory of the event; at the same time, new neuronal branches and enhanced LTP facilitate the amygdala’s implicit memory machinery. In subsequent situations, the amygdala might respond to preconscious information—but conscious awareness or memory may never follow...such a mechanism could underlie forms of free-floating anxiety. It is interesting that these structural changes come about, in part, because of hormones secreted by the adrenal glands, a source well outside the brain. As mentioned, the amygdala’s perception of stress ultimately leads to the secretion of epinephrine and glucocorticoids. The glucocorticoids then activate a brain region called the locus coeruleus. This structure, in turn, sends a powerfully activating projection back to the amygdala, making use of a neurotransmitter called norepinephrine (a close relative of epinephrine). The amygdala then sends out more CRH, which leads to the secretion of more glucocorticoids. A vicious circle of mind-body feedback can result'.

Sapolsky

"I DO NOT WANT to conclude this article having given the impression that anxiety and depression are “all” or “only” about stress. Obviously, they are not. Both illnesses have substantial genetic components as well. Genes code for the receptors for dopamine, serotonin and glucocorticoids. They also code for the enzymes that synthesize and degrade those chemical messengers, for the pumps that remove them from the synapses, for growth factors like BDNF, and so on. But those genetic influences are not inevitable. Remember, if an individual has one of the major psychiatric disorders, her identical twin has only about a 50 percent chance of having it. Instead the genetic influences seem to be most about vulnerability: how the brain and body react to certain environments, including how readily the brain and body reequilibrate after stress. Experience, beginning remarkably early in life, also influences how one responds to stressful environments. The amount of stress a female rat is exposed to during pregnancy influences the amount of glucocorticoids that cross the placenta and reach the fetus; that exposure can then alter the structure and function of that fetus’s hippocampus in adulthood. Separate a newborn rat from its mother for a sustained period and it will have increased levels of CRH as an adult. Seymour Levine, one of the giants of psychobiology, illustrates this point with a quotation from William Faulkner: “The past is not dead. It’s not even the past.” An understanding of the role of stress in psychiatric disorders offers much. It teaches us that a genetic legacy of anxiety or depression does not confer a life sentence on sufferers of these tragic diseases. It is paving the way for some new therapies that may help millions. Given that there is a continuum between the biology of these disorders and that of the “normal” aspects of emotion, these findings are not only pertinent to “them and their diseases” but to all of us in our everyday lives. Perhaps most important, such insight carries with it a social imperative: namely, that we find ways to heal a world in which so many people learn that they must always feel watchful and on guard or that they must always feel helpless''

Sapolsky.