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Paper Response #1: The Role of Neurogenesis on Antidepressant Action

WEEK 1: Jan. 13 Papers (Santarelli et. al, Bessa et. al)

The Santarelli et. al and Bessa et. al papers both investigated whether the behavioral effects of antidepressants (ADs) were dependent on neurogenesis in the hippocampus. At first glance, it appears as though these two papers report contradicting results. Santarelli argues hippocampal neurogenesis is essential for ADs to ameliorate behavioral symptoms of depression, while Bessa refutes this, instead proposing neuronal remodeling and synaptic plasticity as the mechanisms through which ADs take action. However, I believe that these two papers might not be contradictory, and actually compliment one another, with the Bessa study going one step further than the Santarelli study to paint a broader picture of depression and its many symptoms and causes.

One of the main differences between the two studies is that Santarelli’s experiment focused solely on feeding latency on the Novelty-Suppressed Feeding Test (NSFT) as a behavioral measure of depression, while Bessa’s investigation examined a variety of behaviors across different testing paradigms, namely the Sucrose Preference Test (SPT), the Forced Swimming Test (FST), and the NSFT. These tests measured anhedonia, learned helplessness, and anxiety-like behaviors respectively.

Both studies found that feeding latency in the NSFT was only reduced by ADs when neurogenesis was present. In this regard, Bessa’s study does not contradict the results of Santarelli’s study, but actually confirms them. However, Bessa rejects Santarelli’s generalization of this finding to apply to all mood improvements resulting from AD treatment. Instead, Bessa engages in more rigorous testing than Santarelli, and shows that while neurogenesis must occur for ADs to ameliorate anxiety-like symptoms, it is not necessary for them to have an effect on anhedonia or learned helplessness. Bessa further argues that the anxiety-like symptoms measured by the NSFT alone are not a proper determinant of general depressive symptomatology nor is their alleviation a true measure of antidepressive action.

Overall, Bessa’s study tests more rigorously and more broadly than Santarelli’s. It confirms Santarelli’s direct findings, but refutes the generalized conclusions the experimenter draws from these as well as the interpretation of anxiety alleviation as comprehensive evidence of antidepressive action, particularly because depression involves a myriad of other symptoms such as anhedonia and learned helplessness that Santarelli did not touch upon. In line with this, I think Bessa’s paper does a good job at recognizing the multifactorial nature of depression and how it has many causes and symptoms that, in turn, are the product of not just one process (neurogenesis), but several different mechanisms, including neurogenesis but also neuronal remodeling and synaptic plasticity. I see the Bessa paper not as a contradiction of past studies, but as building upon Santarelli’s research and taking it to the next level, where depression is examined under a wider lens that better recognizes its complexity. Going forward, it would be important to run similar studies to further our understanding of the mechanisms behind other symptoms of depression not examined in either of these papers, so that we may uncover more potential causes of depression and continue to build a more comprehensive understanding of this disorder.

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