The serotonergic hypothesis of depression

Depression is, along with anxiety disorders, one of the most common and well-known disorders or psychopathologies in history. Research on what exactly it is and its causes is therefore very relevant to the scientific community and the general population. From the data reflected by the research, a large number of explanatory models have been proposed which take into account both biological and environmental factors.

Attempts to explain depression as a product of problems with balance or levels of certain neurotransmitters are common among the former. And among these hypotheses we find one of the most popular and recognized the serotonergic hypothesis of depression.


    Serotonin is one of the main and most well-known neurotransmitters found in the brain. This hormone, which in addition to the nervous system can be found in other bodily systems (in fact, most of the serotonin in our body is found 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 food.

    Among the many functions it performs, it is considered to be related to the regulation of circadian rhythms and energy levels (especially due to its significant presence in suprachiasmatic, ventromedial and paraventricular nuclei), thermal control, appetite, libido, relaxation and being and comfort. It is also considered to be one of the main hormones associated with maintaining mood, being altered in those with depression issues.

      Serotonergic hypothesis of depression

      The serotonergic hypothesis of depression is one of the most well-known biological hypotheses trying explain the causes of depression. He suggests that the causes of depression are a deficiency or lack of serotonin in the brain. This theory is based on the role of serotonin in regulating mood, indicating that a decrease in serotonin levels in the nervous system or at key points such as the limbic system is responsible for depressive symptoms.

      Likewise, the so-called permissive hypothesis of serotonin indicates that the alteration and decrease in serotonin in the brain cause a deregulation other neurotransmission systems, such as norepinephrine. It is part of the monoaminergic hypotheses, which suggest that the mental disorders of depression are due to a dysfunction, synthesis or transmission of neurotransmitters such as serotonin and catecholamines (dopamine and norepinephrine).

      pharmacological treatments

      Different models and techniques have been used to treat depression, both in terms of psychotherapy and pharmacology. In this last aspect, the main psychotropic drugs used for the pharmacological treatment of depression are those which regulate or modify the levels of monoamine, being particularly used those which increase the levels of serotonin.

      More specifically today, the most common psychotropic drugs in the fight against depression are SSRIs, specific serotonin reuptake inhibitors. It is a group of drugs whose primary mechanism of action is (as the name suggests) to prevent presynaptic neurons from capturing or absorbing the serotonin they have released, so that it stays in synaptic space and generally increases the level of this neurotransmitter in the brain.

      However, it should be borne in mind that serotonin is not the only neurotransmitter involved, and that there are alternatives that focus on boosting the levels of other substances whether secondary or primary. For example, drugs are more successful than serotonin increase norepinephrine levels, ISRN, generating an equivalent level of symptomatic improvement.

      It should also be remembered that drug treatment generates changes in the brain that cause symptoms to go away, but they usually do not address the underlying problem that the person himself associates with depression (for example , lack of reinforcers, poor 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.

      Warning: we are talking about a hypothesis

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

      However, it is still true that these deficits are simply linked to depressive symptoms, without having to be the cause. In fact, the causes of depression are not yet fully understood, being generated by the combination of biological and socio-environmental elements. Other neurotransmitters linked to depressive symptoms or may be involved in its improvement, such as norepinephrine, dopamine or GABA, have also been found.

      Therefore, it should not be assumed that the serotonergic hypothesis describes the ultimate cause of depression, as many factors play a role in its genesis. This is why today the serotonergic hypothesis has lost power and came to be seen not as the cause of depression but as the generator of a biological vulnerability to it.

      The serotonergic hypothesis and the use of drugs such as SSRIs have been the subject of much criticism, among other things for the fact that too much attention has focused on them and severely limited the development of other models and drugs. The debate over the actual effectiveness of antidepressants in treating the problem itself is also widely known.

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