Week 1

After reading the papers, I felt as though Santarelli et al. was looking for a specific answer while Bessa et al. researched the topic in order to learn more about it. I started with the Santarelli et al. paper, and at first glance, I was almost convinced by their results. Then, I arrived at the discussion, which tried to force good data into explaining conclusions it could not fully support. I was mainly stricken by the caveat to the strong relationship they found between behavior and neurogenesis, stating that a 28-day ablation of neurogenesis led to no behavioral deficit in the mice. They brushed it off, but for a paper that just claimed neurogenesis was the missing link explaining how antidepressants work, it seems extremely suspicious that its absence had little effect on the same behavior.

I went through the paper again and found other points that bothered me. Irradiation seemed an aggressive method to block neurogenesis. Even though they checked themselves by showing that irradiated mice had similar baselines to control mice, irradiation affects much more than neurogenesis and an unknown factor could have actually been the reason for the results. Also, the assumption is made that these results could be applied to all antidepressants, when fluoxetine was the only drug considered throughout the whole paper. It is quite the over-statement to implicate something about the treatment of a disease and its mechanics from the results of one drug that works in a very specific manner. Lastly, the paper introduces the pre-frontal cortex as being involved in depression along with the hippocampus, and then fails to research it or even mention it again.

Reading Bessa et al. I was overwhelmed in comparison, but impressed with how broad and thorough the work was. Multiple antidepressants were tested and methylazoxymethanol (MAM), a more reliable method to block neurogenesis in my opinion, was used. I also liked how the researchers were not trying to disprove the involvement of neurogenesis, but attempting to understand its role. Bessa et al. even gave a nod of acknowledgement to Santarelli et al., and it was nice to see that even published researchers can confuse correlation with causation. I would love to see more research addressing the effects antidepressants have on neuronal modeling without playing with the process of neurogenesis.

After reading these, I think it would be interesting to utilize behavioral genetics and apply it to the same concepts and questions. One could use a genetic approach to model depression in an animal instead of putting it in a chronic mild stress paradigm. Would a mouse that was genetically engineered to exhibit depressive behaviors have similar levels of neurogenesis when given antidepressants? How would neuronal modeling and plasticity be different in that mouse? I’d be curious to see if and how the results would differ if the actual model of depression were to be changed.