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The serotoninergic hypothesis of depression

The serotoninergic hypothesis of depression

February 8, 2023

Depression is, along with anxiety disorders, one of the most common disorders and psychopathologies known worldwide throughout history. The research regarding exactly what it is and what causes it is therefore very relevant for the scientific community and for the population in general. From the data reflected by the research, a large number of explanatory models have been proposed that take into account both biological and environmental factors.

Among the former, there are frequent attempts to explain depression as a result of problems in the balance or the levels of certain neurotransmitters. And among these hypotheses, one of the most popular and recognized find the serotoninergic hypothesis of depression .

  • You may be interested: "Major depression: symptoms, causes and treatment"


Serotonin is one of the main and most known neurotransmitters present in the brain. This hormone, which in addition to the nervous system can be found in other body systems (in fact most of the serotonin in our body is outside the nervous system, especially in the digestive tract), was one of the first neurotransmitters to be identified . It is synthesized from tryptophan, which in turn can be introduced into the body through the diet.

Dentre of the numerous functions performed, is considered linked to the regulation of circadian rhythms and energy levels (especially due to its significant presence in the supraquiasm√°tico, ventromedial and paraventricular nuclei), thermal control, appetite, libido , relaxation and feelings of well-being and comfort. It is also considered one of the main hormones linked to the maintenance of mood, being altered in those people who have depressive problems.

  • Related article: "Serotonin: 6 effects of this hormone in your body and mind"

Serotoninergic hypothesis of depression

The serotoninergic hypothesis of depression is one of the most known hypotheses of biological type that try explain the causes that depression can have . It proposes that the causes of depression are a deficit or lack of serotonin in the brain. This theory starts from the role of serotonin in the regulation of mood, indicating that a decrease in serotonin levels in the nervous system or in key points such as the limbic system would be responsible for depressive symptomatology.

Also, the so-called permissive hypothesis of serotonin indicates that the alteration and decrease of serotonin in the brain generates a dysregulation of other neurotransmission systems, such as that of noradrenaline. It is part of the monoaminergic hypothesis, which state that the mental alterations characteristic of depression are due to a malfunction, synthesis or transmission of neurotransmitters such as serotonin catecholamines (dopamine and noradrenaline).

Pharmacological treatments

When treating depression, different models and techniques have been used, both at the level of psychotherapy and at the pharmacological level. In this last aspect, the main psychodrugs that are used for the pharmacological treatment of depression are those that regulate or alter the levels of monoamines, being especially used those that increase serotonin levels.

Specifically today the most common psychotropic drugs at the time of combating depression are the SSRIs, Specific Inhibitors of Reuptake of Serotonin. It is a group of drugs whose main mechanism of action is (as the name says) to prevent presynaptic neurons from recapping or absorbing the serotonin they have emitted, so that it remains in the synaptic space and the level of This neurotransmitter in the brain.

Despite this, we must bear in mind that serotonin is not the only neurotransmitter involved, and that there are alternatives that focus on the stimulation of the levels of other substances, whether secondarily or principally. For example, drugs that are more than serotonin are more and more successful increase norepinephrine levels , the ISRN, generating a level of equivalent symptomatic improvement.

Nor should we forget that pharmacological treatment generates changes in the brain that cause symptoms to be reduced, but that generally do not treat the underlying problem that the person himself links to depression (for example the absence of reinforcers, low perception of control, prolonged stress or anxiety). Psychological therapy has been shown to be more effective in the long term , which suggests that depression is not a purely serotonergic problem.

Caution: we are talking about a hypothesis

The existence of alterations in serotonin levels in the brain is somewhat documented, and it is assumed that one of the main neurobiological problems presented by patients with depression is a deficit of serotonin. It has also been observed that the decrease in the levels of this hormone generates depressive symptomatology .

However, it is still true that these deficits are simply linked to depressive symptomatology, without having to be the cause. In fact, the causes of depression are not yet fully known, being generated by the combination of biological and socio-environmental elements. Likewise, other neurotransmitters related to depressive symptomatology have been found or that can participate in their improvement, such as noradrenaline, dopamine or GABA.

Thus, it should not be assumed that the serotoninergic hypothesis describes the ultimate cause of depression, since there are many factors that play a role in its genesis. That is why today the serotoninergic hypothesis has lost power and has come to be seen not as a cause of depression but as a generator of a biological vulnerability to it.

The serotoninergic hypothesis and the use of medications such as SSRIs have received numerous criticisms, among other aspects due to the fact that they have focused too much attention on them and have greatly limited the development of other models and drugs. The debate about the real effectiveness of antidepressants when dealing with the problem itself is also widely known.

How Did The Public Come To Believe The Low Serotonin Theory Of Depression by Robert Whitaker (February 2023).

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