Major depression has been shown to cause structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis. In fact, in some cases, major long-term depression can cause the hippocampus to shrink by almost 20%. This hippocampal atrophy may result from increased secretion of cortisol, which is found in almost half of seriously depressed patients.
A European group has tested the efficacy of a modified tricyclic antidepressant, tianeptine, in preventing hippocampal atrophy. The group used adult male tree shrews, a model considered to have high validity for studying the pathophysiology of major depression. Animals were subjected to a seven-day period of psychosocial stress to elicit stress-induced endocrine and central nervous alterations before they were given daily oral administration of tianeptine. The psychosocial stress continued over a period of 28 days. Interestingly, the physiological stress effects were prevented by the simultaneous administration of tianeptine. Not only does the study suggest that tianeptine may be useful for the treatment of major depression, it also provides a model for evaluating antidepressant treatments with regard to the possible reversal of structural changes in brain that have been reported in depressive disorders.
- Boldizs C, Michaelis T, Watanabe T, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.211427898.
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