As you may know depression is one of the most common mental health disorders and affects millions of people globally. Either you or someone around you will likely struggle with it in your lives. One basic idea that seemed certain for a long time is that this disorder is associated with abnormally low serotonin in the brain. However, a recent umbrella review incorporating results from several dozen studies has shed new light on this assumption.
But let’s start from the beginning. Serotonin is a neurotransmitter in your brain that is linked to many functions, such as the cognition, reward, learning, memory, and even bodily processes such as vomiting. Most likely you have heard about people with depression (or more specifically MDD, major depressive disorder) having brain serotonin levels that are too low. And indeed, one of the roles that serotonin plays is in the regulation of our moods. However, given many recent research publications, the idea of MDD patients having low serotonin is actually questioned by more and more scientists. Of course, whether serotonin is an important component in depression also affects how we think about the effectiveness of SSRIs (‘selective serotonin reuptake inhibitors’), the major pharmacological treatment of depression. So, the authors of an umbrella review published in 2022 set out to collect as much relevant evidence as possible to figure out whether there is a connection between serotonin and depression after all.
An umbrella review is essentially a meta-analysis of several meta-analyses; and a meta-analysis is just a study where several studies’ results on the same topic are combined and compared. Essentially, what they investigated was whether people with depression have lower serotonin levels or activity than healthy people. To test this, they analyzed data from several studies where serotonin or its major metabolite (a basic building block of serotonin) were measured in blood samples of participants. Combined results from 21 individual studies were that depressed patients really didn’t have lower serotonin levels than healthy individuals.
If you’re already somewhat familiar with the brain and its neurotransmitters, you may suspect that the picture is actually a bit more complicated than just measuring how much serotonin someone has in their brain! Maybe you have read our database articles on the synapse and serotonin, and know that how many (auto)receptors you have for a certain neurotransmitter can impact how much of this neurotransmitter is available in your brain. Thus, if you have more or less serotonin receptors, more or less serotonin becomes available to your neurons, even though the amount of serotonin in your brain doesn’t actually change. Well, the authors of the umbrella review were definitely well informed of this effect. But even after consulting many more studies, they found that there were alsol really no major differences between healthy and depressed people regarding serotonin receptors. Other factors that can determine serotonin availability are the amount of serotonin transporters at the synapse, and certain genetic differences. For these factors also no relation was found with depression!
Wow, so where did this idea of low serotonin and depression come from then? Well, a significant relationship that the umbrella review did find is that the use of SSRIs, both for people with and without depression, was associated with generally lowered serotonin levels. Plus, the authors caution that many of the meta-analyses and studies they read on a daily basis do not control for the medication use of their subjects. That is, they do not select only patients that are either taking or not taking medication. Therefore, this may have skewed the results of many older studies on the topic, and might have led to the false link between depression and low serotonin. Even worse, this may still be going on in entirely different research looking into other mental disorders.
So, remember kids, always control for medication use in your empirical pathology studies!
Author: Melanie Smekal