Depression: a chemical imbalance?

Depression: a chemical imbalance?

80% of the general public believes that depression is caused by a chemical imbalance. A scientific publication reveals that this data remains to be proven.

Dr. Charlotte Tourmente

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Depression: a chemical imbalance?

While it affects one in five people, depression remains poorly understood.

“The idea that depression is the result of chemical abnormalities in the brain, particularly serotonin, has been very influential for years. This idea provides an important rationale for the use of antidepressants. Despite this influence, no scientific journal has ever synthesized the evidence.”

This is how the authors of a publication dated July 20, published in Molecular Psychiatry. They analyzed all the systematic reviews or meta-analyses on the subject (these are works analyzing all the studies published in a field).

“In understanding depression and the effect of antidepressant treatments, the main hypothesis is called the ‘serotonin hypothesis'”clarifies Professor Florian Ferreri, psychiatrist. “In other words, the lack of cerebral serotonin would explain the depression and the effectiveness of antidepressants would be explained by the fact that they increase the level of cerebral serotonin. However, we know that other neurobiological mechanisms are in question.”

The role of serotonin not proven

The conclusion of the authors of the publication is without appeal. “The enormous research in humans on the role of serotonin in depression has not produced convincing evidence on the biochemical origin of depression.”

“The serotonergic hypothesis is old and is not an absolute truth. The studies on this subject are very heterogeneous. It is clear that we do not have a very high level of evidence on the fact that serotonin is massively and permanently disturbed in depression!”

Data already known

This publication is of the “umbrella study” type so it summarizes the various reviews published on the subject”, puts Professor Florian Ferreri into perspective. “So it’s not bringing new data but compiling it for more up-to-date insight.”

By the authors’ own admission, the publication has limits: the reliability of this analysis is linked to the methodological quality of the studies included, which is not perfect. The number of participants is small, limiting the scope of the results.

“The authors only selected studies on humans, knowing that we also rely on animal data”also specifies Professor Ferreri.

Depression, a disease with multiple causes

The contribution of this publication remains important. This is the first “umbrella study”, compiling the data available to date on the role of serotonin. “The authors point out two important things”, summarizes Professor Ferreri. “First of all, although the theoretical model of serotonin is interesting, we still need many studies to confirm the serotonin hypothesis in humans. It also shows that this is not the only hypothesis to explain the disturbances of depression.

A postulate that has been known for several years since other mechanisms have already been put forward.

“Depression involves neuromediators other than serotonin such as norepinephrine and dopamine, but also phenomena of inflammation and cerebral plasticity, as well as receptors such as the NMDA receptor and GABA”says the psychiatrist.

The environment, through stress factors (such as unemployment or separation), also intervenes, knowing that we do not all have the same ability to manage them. Genetic vulnerability probably plays a role since a person whose parent is depressed is 2 to 4 times more likely to have depression according to Inserm.

New treatments and techniques, a major challenge

Depression has not yet revealed all its secrets and even less all its mechanisms.

Concerning the treatment with antidepressants, there are several classes of them acting on different mechanisms. One of them targets serotonin. If the publication believes that antidepressants are not effective, a number of meta-analyses show that they are more effective than a placebo and provide relief to many patients. Taking antidepressants must often be associated with psychotherapy in severe depression.

This publication allows us to remain humble in what we know about depression”, concludes Professor Ferreri. It shows the need to develop new drug strategies using pathways other than serotonin, such as ketamine. It also encourages the use of new brain stimulation techniques such as repeated transcranial magnetic stimulation, rTMS”.

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