Santanelli et. al

The Santarelli et al. paper drew the conclusion that the behavioral effects of chronic antidepressant treatment require neurogenesis in the hippocampus based on the findings that mice treated with antidepressants have decreased latency to feed and increased neurogenesis. The researchers go on to find that hippocampal neurogenesis is involved in the mechanism by which antidepressants function, but fail to discuss the mechanism itself. It would seem the researchers proved there is a significant correlation between chronic antidepressant treatment and hippocampal neurogenesis but not causation. I would have liked to learn what, if any, structural or chemical changes occurred after chronic administration of an antidepressant that promotes neurogenesis. Bess et al. mention antidepressant-induced hippocampal neurogenesis may be an epiphenomenon. Based on the results of both papers I think this is a reasonable conjecture. Santarelli et al. clearly demonstrates that neurogenesis significantly contributes to the effects of antidepressants but fails to show evidence that hippocampal is the sole mechanism driving the antidepressant effects.

Santarelli et al. references a study (van Praag) in which researchers found in the adult mammalian dentate gyrus new neurons are functionally integrated into hippocampal circuit. van Praag et al. offer two potential explanations as to what the new neurons are doing, either by replacing the old dying neurons, or by providing alternative pathways for plasticity. Based on the finding of the two papers it is clear that antidepressants promote neurogenesis, but Bessa et al. claims that neuronal remodeling and synaptic plasticity, rather than neurogenesis, serve as the basis for the behavioral restoration of homeostasis during antidepressant treatment. I offer the alternative hypothesis that it is both processes that drive the behavioral efficacy of antidepressants. It is possible that acute antidepressant treatment begins the reorganization of neural circuits, and that prolonged, chronic treatment of antidepressants further promotes the behavioral effects via neurogenesis, but is not required. The new neurons formed may serve to both replace the atrophied neurons as they are integrated into the re-organized neural circuit. I believe in the future it would be informative if the timescale of the neural organization, synaptic plasticity, and neurogenesis were studied and analyzed in order to determine if neural plasticity the coupling of these processes affects the onset of the behavioral effects of antidepressants.