The dominant serotonin hypothesis has been put to the test by science

Let’s ride a time machine: It’s 1967 when the title of the article was Biochemistry of affective disorders It was published in the scientific literature by Alec Cobain. He was the first to put forward the idea that depression and other disorders might have a biological explanation. In a viewfinder, monoamines (including dopamine and the serotonin), which is a family of neurotransmitters Their jobs are different. If the proposed model does not escape the environmental causes of these disturbances, it focuses on the rigorous biochemical aspect of their explanation. The idea that there would be a loss of neurotransmitters that would cause the disturbances, already exists.

While the article is innovative in that it suggests quantifiable causes of affective disorders, the evidence it has to support its view is scant. What drives the author to suggest that these disorders have biochemical bases is the fact that therapies ” physical Working. Then he takes the patient’s case as an example My depression, lagging behind and loss of appetite” It is suggested that he regained his normal state afterwards seizures From Electric current. Of course he does not stop there at the demonstration. But most of the studies cited include a small number of patients, limiting the theory to a clear exploratory stage.

Since then, numerous studies have been conducted with the aim of revealing the biochemical basis of depression, with a particular focus on serotonin. If this theory has been validated by many in the media and for health professionals who are not specialists in the topic, there are still questions about it in the scientific community. With this in mind, a recent systematic review has been published in temper nature Fits, arguing that this theory is simply not supported by empirical evidence.

Why is this important?

As we just mentioned, this theory enjoys a special status due to its extensive media coverage since the 1990s and the marketing of serotonin reuptake inhibitors. This can greatly affect people’s beliefs about the supposed causes of depression. For example, in Australia, 67% of the population is a trait Depression has neurobiological causes. However, most people think too There are psychosocial reasons.

Some consider the definitive evidence for this theory to be the clinical efficacy of serotonin reuptake inhibitors. However, the latter is regularly subject to criticism, both in issue The magnitude of the effect and the relative effectiveness depending on the severity of depression and even the mechanisms of action. A good overview of these reviews can be found at This meta-analysis Who studied extensive clinical data sent to Food and Drug Administration. With all these elements, it is thus necessary to check the status of this theory in the literature. Has it been validated by strong, consensus-based evidence? Do you refute? Or should it be the subject of a broader investigation?

The burden of proof falls on the scientists who support this theory

Within their systematic review, the authors examined the association between serotonin and depression by taking into account the level and level of plasma serotonin. metabolite Major urinary tract:sour 5-hydroxy-indoleacetic acid, level and activity of serotonin synaptic receptors, level and activity of serotonin transporters, lowering effect on tryptophan — I’Amino acid Introduction of serotonin – at the onset of depression, the level of expression of a embarrassed interest, particularly those that lead to the production of protein Serotonin transport and interaction between this gene and Stress. The authors excluded studies in animal models and patients with certain conditions (Patients or very specific depression such as childhood or postpartum depression).

Regarding serotonin and its urinary metabolite, the review indicates that the associations are not statistically significant when multiple regressions were performed, given the importance of other key variables. Some studies have also investigated this association by measuring the above-mentioned variables in cerebrospinal fluid – Preferred site for this kind of measurement, but it’s very invasive – and no link found. On the receptor side, of which more than 14 have been identified, the review focuses on studies of only one of them, as they are currently the only ones that could potentially play a role in the occurrence of depression. There is no detectable association between healthy patients and depression. Also, there are unfortunately many methodologically biased studies, as they include patients undergoing treatment.

For the carrier, studies do not find associations and when they do find some, they suffer from a massive systematic bias that most patients included had a history of takingAntidepressants. It’s a common problem in depression studies that was already limiting results in Alec Coppen’s days. studies depletion, which focuses on lowering tryptophan intake, suffers from the same bias, and in more qualitative studies, it found no effect on participants’ mood. Finally, about the part hereditary isolated and its relationship to stress, if previous studies indicated that there are links between a genetic polymorphism and depression, larger, more methodologically robust studies have failed to reach the same results. So these links are very questionable.

What future for the theory of neurobiological imbalance?

Given the items presented, the neurobiological imbalance theory does not appear to be supported by evidence. However, there are several things that need to be clarified. The first is that this theory can still explain other types of depression. As we have seen, studies including this type of patient were excluded from the systematic review. Second, other signs may provide conflicting clues in the future, such as the 13 future ones whose functions we still don’t know very well today. Third, no matter how reliable this theory is, it does not questionaxiom This suggests that depression has biological causes.

Therefore, even if this theory is wrong, it does not reconsider the outdated ideas, which unfortunately are still very prevalent, considering that depression is caused by a lack of will. Unfortunately, partial biological determinism, even when it is known, Doesn’t seem to reduce stigma In the population with mental disorders. In conclusion, so proponents of this theory have to provide more convincing evidence to support it. The medical community should also re-examine some drug treatments whose controversial clinical efficacy is based on this theory.