Week 1: mechanism of antidepressants

Before starting to read both articles, I wanted to gather the information I already learned about the mechanisms of using antidepressants to treat depression. For starters, I understood that depression can be caused by a chemical imbalance of serotonin and/or norepinephrine (which I later came to learn is the monoaminergic hypothesis of depression). Antidepressants are then used to either provide the missing neurotransmitters or to block the reuptake of the already present neurotransmitters. Now ready to read the two articles of the week, I wanted to learn exactly how antidepressants work to effectively treat depression symptoms?

In the Santarelli et al. article, they suggested that antidepressants relieve depression symptoms by having an exclusive relationship with neurogenesis in the hippocampus. Where I want to believe the simple explanation of depression being treated with the development of new neurons, I found it hard to follow the execution of the study. First, they used mice that did not have any previous symptoms of depression and inflicted a series of stress-inducing tests on them. Are stress and depression the same thing in this model? Second, if stress causes atrophy of neurons in the hippocampus and antidepressants work only if neurogenesis is present, does this mean that there is no way of salvaging already present mature neurons? Do new neurons constantly have to be produced in order to replace damaged neurons that no longer work? Are the new neurons produced using antidepressants the same as the neurons already present? I believe this article’s hypothesis could have been made stronger if it addressed some of these questions or clarified, in more detail, their tracking of the neurogenesis. The Bessa et al. article provided not only some answers to my questions but also a more reasonable hypothesis to how antidepressants work. They used mice that were already introduced to a chronic mild stress paradigm before being tested with multiple stress tests. Their hypothesis that antidepressants work to repair damaged neurons was a realistic theory because it provided scientific proof of NCAM1 expression to back it up.  Although neurogenesis does increase in the presence of antidepressants, is it the sole mechanism to how antidepressants treat depression? I believe the brain is very complex and one simple explanation to a disease doesn’t seem like the likely answer. More research must be done in order to understand the disease and its mechanism.