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MECHANISM OF ACTION One possible cause of the hippocampal damage seen in depressed people is stress. Stress apparently interacts with depression to shrink existing neural cells and limit growth of new ones. Stress and depression exert this control in part through a cellular signaling cascade involving cyclic adenosine monophosphate (cAMP) and the associated cAMP response-element binding protein (CREB).

Duman has found evidence that antidepressants counteract the deleterious effects of stress and depression by boosting activity in the cAMP pathway, which in turn upregulates, or cranks up, the pathway for the gene transcription factor CREB. This increases expression of neurotrophic factors that enhance survival of neural cells. Antidepressants also appear to increase production of new neural cells through the cAMP-CREB pathway
UPDATE 02.04
AUTHOR Ronald S. Duman, professor of psychiatry and pharmacology and director of the molecular psychiatry division at Yale University's School of Medicine.

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