Cell atrophy and loss in depression: reversal by antidepressant treatment

Depression is associated with structural alterations in limbic brain regions that control emotion and mood. Studies of chronic stress in animal models and postmortem tissue from depressed subjects demonstrate that these structural alterations result from atrophy and loss of neurons and glial cells. These findings indicate that depression and stress-related mood disorders can be considered mild neurodegenerative disorders. Importantly, there is evidence that these structural alterations can be blocked or even reversed by elimination of stress and by antidepressant treatments. A major focus of current investigations is to characterize the molecular signaling pathways and factors that underlie these effects of stress, depression, and antidepressant treatment. Recent advances in this research area are discussed and potential novel targets for antidepressant development are highlighted.

► This manuscript highlights recent studies demonstrating cellular and structural changes associated with stress and depression.
► A major focus of research efforts has been characterization of the signaling pathways underlying the structural alterations caused by stress and depression.
► Evidence that the structural alterations are reversible upon removal of stress or by antidepressant treatment is presented.
► Elucidation of the mechanisms underlying the ameliorating effects of antidepressants is discussed.
► Recent evidence that fast acting antidepressant agents rapidly reverse the structural deficits caused by chronic stress exposure is presented.