Depression has no direct relationship with low serotonin levels, research says

A new paper points out that there is not enough evidence to confirm a direct association between low serotonin levels and the development of depression. The conclusion of the study has repercussions on questions about the treatment of psychiatric disorder, since antidepressants act based on this understanding.

The article was published this Wednesday (20) in the journal Molecular Psychiatry. It is a systematic review –analysis of other previous studies– and is composed of 17 studies that had already been carried out.

Serotonin, popularly called the happiness hormone, is a neurotransmitter that acts in several areas of the human body, such as mood and sexuality. For people with depression, it was found that drugs – called serotonin reuptake inhibitors – that act to increase this substance had positive effects in the treatment of the disease.

These beneficial results resulted in a realization that low serotonin levels would be a major cause of depression. What the new research suggests is that there is not enough evidence to define this.

The authors observed, based on the results of other investigations, that not all patients with depression had a low level of serotonin, that is, the depressive condition would be associated with other factors.

It was also observed that the use of methods to reduce serotonin in individuals without the condition did not result in a depressive condition.

The findings reiterate that low serotonin levels are not necessarily a cause of depression.

Rogério Panizzutti, psychiatrist and professor at the Institute of Psychiatry (Ipub) at UFRJ (Federal University of Rio de Janeiro), says it is important to identify other reasons that may be related to the development of the disease.

“It’s a rather simplistic explanation that the problem with depression is the drop in serotonin,” he says, who is not one of the authors of the research.

Panizzutti says that there are antidepressants that act on other neurotransmitters, such as dopamine, which suggests that there are other substances involved in the disease. “All [esses remédios] have a similar outcome which is the treatment of depression.”

Christian Dunker, psychoanalyst and professor at the Institute of Psychology at USP (University of São Paulo), points out that it is necessary to understand the development of depression from other fronts than just the search for a biomarker that would explain the depressive condition.

“The idea took hold that depression had no deeper relationship to the way of life,” says Dunker, who is the author of “A Biography of Depression” and did not sign off on the new research.

This view, however, has come to be questioned. The psychoanalyst says that some neuroscience research has pointed out that there is an interaction between the brain and the environment in which the person lives. In this way, depression would not be a strictly biological phenomenon, but would involve other issues of the individual and the environment that surrounds him.

Therefore, he considers that the new research is important for opening a range of possibilities in the study of depression and also of other psychopathologies.

Mechanism of drugs

In addition to concluding that evidence is lacking to confirm the causal relationship between serotonin and depression, the research reiterates that it is necessary to better understand the mechanisms of serotonin reuptake inhibitors.

One of the points is that, as the development of depression does not necessarily result from low levels of the neurotransmitter, the inhibitors would not be acting directly on the cause of the disease.

The authors also say that a study analyzed in the systematic review observed a decrease in serotonin with long-term use of antidepressants. Therefore, it would be necessary to develop new research to understand more clearly the effects of these drugs in the treatment of the disease and how they act in the human body.

The points are still the subject of debate.

For Dunker, doubts about the mechanisms of antidepressants can generate certain doubts about the results of these drugs. “Since we don’t know how they work, it could be that they are working on causes or side effects,” she says.

Panizzutti reiterates that drugs acting on other neurotransmitters also have positive effects in the treatment of the disease. For him, this would be an indication that “it is probably not that all these neurotransmitter systems are defective in depression, but that, by altering their action, an antidepressant effect is achieved.”

That is, even not acting directly on the cause of the disease, these drugs cause an improvement in the patient’s clinical condition, says Panizzutti. “That’s what matters to the person who is suffering from the mental disorder.”

Marcelo Feijó, who did not sign the study and is a professor in the department of psychiatry at the EMA (Escola Paulista de Medicina) at Unifesp (Federal University of São Paulo), says that the drug’s actions are still subject to research.

“We don’t have all the knowledge of what [o inibidor] produces inside the brain”, he says.

An initial explanation for the action of this type of medication was that it would result in an increase in serotonin in the body by inhibiting the reuptake of the substance. But Feijó says that new research points to other mechanisms to understand the benefits of inhibitors.

“Some research says that [o aumento da serotonina] it’s just the beginning of change”, he sums up.

However, this lack of knowledge about the mechanism of these drugs would not be an indication that they would not work, says the professor. “The risk of a study like this is saying that medications that affect the serotonin system would not be effective.”

Feijó says that, on the contrary, research has already indicated the effectiveness of the antidepressant, although it may vary for each patient because depression is a multifactorial disease . “For some people it works super well and for others it doesn’t”, he concludes.