Depression, stress, epilepsy and adult neurogenesis.

Epilepsy and depression share an unusually high coincidence suggestive of a common etiology. Disrupted production of adult-born hippocampal granule cells in both disorders may contribute to this high coincidence. Chronic stress and depression are associated with decreased granule cell neurogenesis. Epilepsy is associated with increased production - but aberrant integration - of new cells early in the disease and decreased production late in the disease. In both cases, the literature suggests these changes in neurogenesis play important roles in their respective diseases. Aberrant integration of adult-generated cells during the development of epilepsy may impair the ability of the dentate gyrus to prevent excess excitatory activity from reaching hippocampal pyramidal cells, thereby promoting seizures. Effective treatment of a subset of depressive symptoms, on the other hand, may require increased granule cell neurogenesis, indicating that adult-generated granule cells can modulate mood and affect. Given the robust changes in adult neurogenesis evident in both disorders, competing effects on brain structure are likely. Changes in relative risk, disease course or response to treatment seem probable, but complex and changing patterns of neurogenesis in both conditions will require sophisticated experimental designs to test these ideas. Despite the challenges, this area of research is critical for understanding and improving treatment for patients suffering from these disorders.