It is generally known that Low serotonin leads to depression , Whereas to treat it one has to try that the levels of serotonina in the organism are high.
Depression is a silent epidemic, one of the most common forms of mental illness within the general population and that in many people it still ends up associating with a weakness of character that, if one wants, can come out perfectly.
This disorder is of great importance to society as a whole, as it affects millions of people around the world.
In general, the prevalence of depression is 15% and is associated with morbidity and mortality in both developed and developing countries.
It is the fifth leading cause of global disability and about 4% of the total burden of disease worldwide and affects at least 20% of women and 12% of men at some point throughout their lives.
In this article you can learn more about what depression is and what role it plays. Serotonin In the aetiology of said disorder.
What is depression?
Depression is a pathology that affects the State of mind , To thought and to the organism (the brain).
It is a psychiatric disorder characterized by an altered mood that permeates all levels of functioning of the person.
The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines the Major Depression As a disorder that includes a set of behavioral symptoms such as:
- A Decreased Mood
- Anhedonia Or decreased pleasure in activities that were rewarding
- Changes in body weight
- Sleep disturbances
- Fatigue or loss of energy
- Psychomotor alterations
- Feelings of excessive guilt or of underestimation
- Decreased concentration
- Thoughts of death or suicidal ideation
What is serotonin?
There are four classes of neurotransmitters (which are molecules that release active neurons and that influence the activity of other cells):
- Amino acids
- Monoamines
- Soluble Gases
- Acetylcholine
The Monoamines Are a class of small molecule neurotransmitters, which are synthesized from a single amino acid (an amine).
The monoamines are present in small groups of neurons and their cellular bodies are located, mainly, in the Troncencephalon .
There are four transmitter monoamines: dopamine, Noradrenaline , Adrenaline and serotonin, which is the subject of this article.
The monoamines are divided into two groups according to their structure: Catecholamines (Dopamine, adrenaline and noradrenaline), which are synthesized from the amino acid Tyrosine And the indolamines (serotonin or 5-hydroxytryptamine or 5-HT) which is synthesized from the amino acid Tryptophan .
The amount that is transported depends on the concentration Which has the individual in the body and the concentration of other amino acids in the body, since all compete to be transported by the same carrier.
Most of the brain's serotonin is formed in the raphe nuclei that is located in structures that make up part of the brain stem.
Given the wide distribution in the brain and also due to the number of receptors, the serotonin system plays an important role in regulating various physiological functions and participates in the cognitive processes And mood control.
Serotonin has an important action on the character, behavior, movement, appreciation of pain, sexual activity, appetite, endocrine secretions, cardiac functions and the sleep and wake cycle.
The wide distribution of serotonergic pathways and the multitude of receptors, more than 15 subtypes, indicate their participation in so many different functions.
What is the role of serotonin in depression?
One of the theories on the biological etiology of depression explains the hypothesis that depression is due to a deficiency of monoaminergic neurotransmitters, among which we find serotonin.
We must refer to the monoaminergic hypothesis of depression.
Major depression is a pathology that has been associated with serotonin when it is confirmed that antidepressants that increase the available levels of serotonin end up producing in patients with depression an improvement of their symptoms.
The evidence for this hypothesis is simple. For example, it was observed that reserpine, a drug used to treat hypertension, caused depression in some patients.
The Reserpine , Which inhibits the storage of monoamines, acts as an antagonist of 5-HT and therefore the idea arises that drugs that inhibit this neurotransmitter (also dopamine and noradrenaline) could induce depression in individuals.
In addition, it is also observed that those drugs that potentiate these three neurotransmitters (act as agonists) improve depressive symptoms. These drugs would be both Tricyclic antidepressants (ATC) as the IMAOS (Monoamine oxidase inhibitors).
This demonstrated that these neurotransmitters were key in treating the disorder we are dealing with, depression.
In addition, it should be noted that other evidence was the fact that the suicidal tendency, present in some patients with depression and that is a diagnostic criterion according to the DSM, was related to the decrease of the levels of 5-Hydroxindoleacetic acid (5-HIAA) in the cerebrospinal fluid .
5-HIAA is a metabolite of serotonin, indicating that they had little neurotransmission of serotonin.
It should be noted that some research and clinical observations were contrary to these hypotheses. For example, some research linked this decrease in 5-HIAA to exclusively violent suicides, so it seemed to have to do with violence rather than with depressive symptoms.
In addition, some drugs or substances that also increase monoamines have no antidepressant effects. It is the example of cocaine, which produces an increase in monoamines and yet does not improve Depressive symptoms .
Attempts were made to induce depressions causing a decrease in serotonin levels, but the results were not convincing.
The administration of high doses of tryptophan in order to raise the concentration of serotonin in the brain also had no effect on the relief of depression.
Another aspect against the hypothesis, and perhaps the definitive one, is the"therapeutic latency"that exists when taking antidepressants.
It refers to the delay in the improvement of symptoms, which takes about 15 days, which indicates that some type of 'brain plasticity' may be produced to respond to this improvement.
Therefore, other hypotheses arise, such as the one that refers to the mechanisms that are involved in the synaptic receptors, which indicates that in the depression there would be an alteration of these.
Thus, there could be an upward regulation, ie higher postsynaptic receptors given that there is less amount of neurotransmitter.
There is some evidence of this. One of these would be that in brains of people who have committed suicide there is an increase of serotonin 5HT2 receptors.
In addition, serotonin would be involved in some depression symptoms and circuits such as depressive mood, sleep disturbances, appetite and weight gain, suicidal ideation and psychomotor symptoms.
The serotonin transporter is a key element in the control of the activity of said neurotransmitter, since it regulates the effective concentration of 5-HT in the Synapses Of the nervous system.
The serotonergic system seems to play a relevant role. Changes in the treatment of depression operate at the pre- and postsynaptic level, in the serotonergic neuron itself or in the receptors that decode the serotonin signal.
The final functional expression of these changes is the increase in serotonin activity in different areas of the central nervous system, limbic system Or the Frontal cortex .
It also comes to question the role of serotonin in depression, as some studies compare the effect of SSRIs , For example, with other treatments not related to serotonin.
Some investigations with bupropion and reboxetine, for example, demonstrated that these were as effective at treating depression as SSRIs, and yet none of them affected serotonin levels.
In conclusion, the data are contradictory and there is no clear evidence corroborating the serotoninergic theory.
Causes of Depression
Although studies have been conducted to find out the etiology and the most appropriate treatments for depression, some of its Pathophysiological mechanisms Are unknown.
Knowledge about How the brain works Within the process of health and illness has been increasing for two centuries.
However, there are some areas within medicine such as cardiovascular diseases whose progress has been much greater when it comes to knowing the pathophysiology. The one of depression, for example, has been much smaller.
Depression has already been clinically recognized by Ancient greeks , But it was about the mid-nineteenth century when it began to study what mechanisms or neurotransmitters were involved in it, something that inevitably led to the development of different treatments.
An important question has been whether depression is a biological disorder or a response to psychosocial stress where the body is unable to cope with it.
Both cases have been recognized as causes within the depression. Certain situations may lead to an individual suffering a depressive episode, multifactorial stimuli that constitute stressors with affective value for the affected person.
He stress Is an important factor in generating a depressive episode; However, this is linked to the biological changes, both physiological and hormonal that are associated with the axis of the hypothalamus-pituitary-adrenal.
Therefore, among the causes of depression are genetic factors, psychosocial factors and chemical factors, that is, neurotransmitter disorders, which is what we are concerned with here.
For example, among the genetic factors, it is worth noting that the risk of morbidity in first degree patients increases in the studies performed and that some genetic markers have been found on different chromosomes, such as 2, 10, 11, 17 and 18 between others.
In addition, some association studies have highlighted the importance of gene polymorphisms such as that of the serotonin transporter in the genesis of depression.
In relation to the neurotransmitters, we can highlight the explanation that abnormal levels of some neurotransmitters such as serotonin (5-HT), Noradrenaline wave Dopamine (Which are neurotransmitters acting on neurons of the central nervous system) may be important in explaining the pathophysiology of depression.
Treatments for Depression
The main treatment of choice is pharmacotherapy, psychotherapy and electroconvulsive therapy.
Antidepressant drugs are classified into: tricyclic antidepressants (TCAs), monoamine oxidase inhibitor antidepressants (MAOIs) and selective serotonin reuptake inhibitors (SSRIs).
We found others such as IRNs, NAINs (NA and DA reuptake inhibitors), IRSNs (NA and 5-HT reuptake inhibitors), NaSSA (specific noradrenergic and serotonergic antidepressants), and ASIR (5-HT 2 antagonists / reuptake inhibitors).
The hypothesis of monoamines as a psychobiological explanation of depression has dominated the knowledge about this disease in recent decades.
The first Antidepressants (AD) initiated the era of treatment in depression, however, both MAOIs and TCAs, the former, were not designed to treat it but their effects were evidenced later.
From the dominant hypotheses the ADs were developed that have been differentiated between them by their mechanism of action and the selectivity on presynaptic and postsynaptic receptors.
In the 1950s, it was observed that iproniazide, a drug to treat tuberculosis Improved mood , Which led to its use being extended to treat depression. It was the first step for the synthesis of MAOIs and to generate it to treat depression.
In 1958 it was found that imimpramine also improved mood and the study of its mechanisms of action allowed to formulate the theory of the monoaminergic hypothesis of depression and synthesize the TCA.
The pharmacological significance of the 5-HT transporter lies in the fact that the first-generation AD, ie tricyclics, inhibited serotonin reuptake to a greater or lesser degree.
Although as we have seen these theories are not conclusively demonstrated and are probably very reductionist, they did allow the development of research in AD and based on theories developed the new ADs, SSRIs.
These drugs have the ability to inhibit and be selective in neuronal reuptake of serotonin by blocking the transporter. They have less side effects and therefore the adhesion in the patients is greater.
The latter, the SSRIs, were developed looking for greater specificity on the serotoninergic system. Some examples are the Fluoxetine , the Paroxetine , Sertraline or Citalopram .
References
- Aguilar, A., et al (2010). Psychopharmacology for Psychology students.
- Artigas, F. (1997). The serotonin transporter as a therapeutic target. Psychopharmacology, 2, 13-19.
- Brenes, J. C. and Rodríguez, O. Stress and depression: neuroendocrine hypotheses. Research articles from the Catholic University of Costa Rica.
- Caruncho, H., Rivera-Baltanás, T. (2010). Biomarkers of depression. Rev Neurol, 50 (8), 470-476.
- Guadarrama, L., Escobar, A., Zhang, L. (2006). Neuro-anatomical and neuroanatomic bases of depression. Rev Fac Med UNAM, 49 (2), 66-72.
- Lacasse, J.R., and Leo, J. (2006). Serotonin and depression: a disconnect between advertising and centric literature. Drug Bulletins, 9 (1).
- List Varela, A. (1994). New antidepressants: selective serotonin reuptake inhibitors. Its impact on the management of depression. Rev Med Uruguay, 10, 178-184.
- Mazzotti, G., Carpio, J. (1996). Serotonin and depression. Journal of Neuro-Psychiatry, 59, 93-101.
- Montes, C. Depression and its etiology: a complex pathology.
- Pinel, J. (2007). Biopsychology. Pearson.
- [Links] Serotonin and mood states. Science and development.
- Travé Rodríguez, A. L., Reneses Sacristán, A. (2002). Management of drugs in the treatment of depression. Therapeutic Information of the Navional Health System, 26, Madrid.