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Major depression. As will be detailed in chapter 14, major depression is utterly intertwined with prolonged stress, and this connection includes elevated glucocorticoid levels in about half the people with major depression. Yvette Sheline of Washington University and others have shown that prolonged major depression is, once again, associated with a smaller hippocampus. The more prolonged the history of depression, the more volume loss. Furthermore, it is in patients with the subtype of depression that is most associated with elevated glucocorticoid levels where you see the smaller hippocampus.