Depression is not related to low serotonin levels

Depression is not related to low serotonin levels

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Although for years it has been believed that low levels of serotonin have to do with depression, a series of studies have not found the relationship between the two.

It’s clear how most drugs work their magic, but not all of them do, and so they become a mystery. Some of the most mysterious are part of the group of antidepressants called selective serotonin reuptake inhibitors or SSRIs, the best known of which is Prozac.

For years, doctors believed that SSRIs worked by raising levels of serotonin, a chemical that carries signals between nerve cells and the brain. This theory was based on the hypothesis that a lack of serotonin causes depression. But more and more studies suggest that this theory is not entirely correct and Molecular Psychiatry has just published a series of analyzes on the matter.

This extensive study, led by Joanna Moncrieff of University College London, covers different aspects of the relationship between serotonin and depression. One of them considers the levels of serotonin and its breakdown products in the blood and spinal cord fluid as approximations to the amount in the brain, since it is dangerous to make these measurements in living people. The study concludes that in this aspect there are no differences between people with clinical depression and healthy people.

The neurons reabsorb serotonin when it has fulfilled its function, the SSRIs block it so that a larger section of the molecule remains available. Therefore, another study looked at the receptor proteins that respond to serotonin and the transporters by which it is reabsorbed.

This sometimes led to higher levels of serotonin activity in people with depression, contrary to what was expected. Dr. Moncrieff admits that this may be due to the use of antidepressants, something that is not always taken into account when comparing people with or without depression.

A third line of study is based on the fact that serotonin comes from tryptophan, a substance that the body cannot synthesize and must be ingested through food. In these experiments, participants’ serotonin levels were lowered by withdrawing tryptophan. Dr. Moncrieff’s team concluded that reducing serotonin in this way did not cause depression in hundreds of healthy volunteers.

Lastly, the researchers considered large genetic analyses. No differences were found between the genes that regulate serotonin transporters in those with or without depression.

If serotonin is not the cause of depression, then questions arise regarding SSRIs. These help some recent patients but not others. And it has its price. Possible side effects include loss of libido and inability to reach orgasm. They also create a kind of dependency and some of the patients recovering from depression take them for life.

For now, clinical practice is transforming to place greater emphasis on environmental triggers of depression such as adversity and lack of response tools rather than medication use. Still, it would be nice to know in advance who might benefit from using SSRIs and who might not. For this, and without the serotonin hypothesis, doctors have to start from scratch.

Translation by Grace Gonzalez

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