Anxiety disorders are the consequence of a decrease in serotonin levels
Not only the serotonin system is involved in anxiety, mood and obsessive-compulsive spectrum disorders. However, speaking specifically of this neurotransmitter, both the hypofunctional condition and the hyperfunctioning condition of the serotonin system can manifest themselves with anxiety symptoms or with other psychic symptoms. In the case of the symptoms of the obsessive-compulsive spectrum, according to some points of view, it would be a condition of “excess” rather than “deficiency”, even if today there is still no defining theoretical version. The main doctrines on the neurochemical mechanism of these disorders have been based for years mainly on the response to specific categories of drugs, such as, antidepressant drugs most closely related to serotonin receptors, and which give rise to an especially initial increase in serotonergic tone. How such drugs actually work in the long term and what causes them to work has been a subject of further research. Today the hypothesis is more accredited that the treatment with selective antidepressants inhibitors of long-term serotonin reuptake, rather than stimulating, modulates the functioning of the serotoninergic system, also reducing any excessive reactivity of this system.
What would be the symptoms of an overproduction of serotonin and if this can, on the contrary, lead to anxiety
It is a bit difficult to give examples that correspond to everyday situations: more often they concern pathological situations.
The classic case of hyperactivity of the serotonin system is the “serotonin syndrome”, a potentially life-threatening situation that can arise following intoxication with antidepressants (taken at toxic dosages), opiates, amphetamines, other drugs and in the case of the combination with a number of other drugs that impact the serotonin system. In such situations the most characteristic symptoms are neurological and of the general state (fever, sweating), but anxiety and agitation can often be present as well. Such intoxication, like drug intoxication in general, is a life-threatening situation and requires the intervention of the emergency health services.
Qualitatively on the same continuum, but very different in their substance are the usually transient side effects in the early stages of therapy with antidepressants that stimulate the serotonin system (the most frequent symptoms are gastrointestinal, neurological, and worsening of psychic symptoms) .
It is interesting that the withdrawal syndrome of serotonergic antidepressants (more frequent if the withdrawal is abrupt) can also manifest itself with similar symptoms. Whether this can be explained by the lack of the “push” of the antidepressant, or rather with a temporary dysregulation of the system kept “within” by the antidepressant, is an open question.
Unlike SSRIs, which in the settling phase no longer lead to serotonergic hyperfunction, the prolonged intake of active substances that do not modulate but above all stimulate the serotonergic system, such as, among others, amphetamines, partly opiates, but not among the last also alcohol, leads to pathologically high levels of serotonin, manifesting itself with the typical signs of use of these substances and with the subsequent signs of deficit of the central nervous system, destroyed and exhausted by stimulation.
Another example is the hypersecretion of serotonin by some neoplastic cells, so called “neuro-endocrine”, which can constitute a form of neoplasm in itself or also be part of the Multiple Endocrine Neoplasms Syndrome …
It is the abnormal proliferation (neo-plastic) and abnormal functioning of the physiologically present cells scattered and in the plexuses especially in the digestive system, in the abdomen, but also in the chest and along the nerve pathways that innervate the internal organs, the cells that can be considered the primitive endocrine glands each composed of one cell. The substances they secrete can also be considered the primitive hormones. The symptoms of the secretory hyperactivity of these tumors known as “carcinoid syndrome” are fleeting but repetitive: mainly intestinal, cutaneous, cardiovascular, respiratory and intestinal, but also anxiety, although it is not the main or most characteristic symptom. In reality, these symptoms are not due only to serotonin, but to a ”
Because, if there was an excess of serotonin in anxiety disorders, this improves with the use of SSRIs, whose main function would be to prevent the pre-synaptic neuron from reuptake serotonin, making sure that the serotonin itself can act in higher concentrations and for longer times on the postsynaptic neuron
This is at the beginning, while subsequently the physiological adaptation of the receptors develops which become less sensitive to serotonin and its excessive secretion, the secretion that during the taking of the drug is in any case more regular unlike what can happen during the course of the decompensated disease (because the problem may not necessarily be a constant defect or excess, but an instability of serotonin secretion: with peaks in the background of normal or low levels, to which the receptors or downstream systems may be too sensitive). However, it is always the theories, more modern than the classical paradigm. Such an adaptation of the system would take some time, and as practice shows, the therapeutic effects manifest themselves after the latency period of a few weeks, that could correspond to such changes, and to make those changes more stable it takes months. However, it is possible that SSRI antidepressants act not only at the synapse level, but also at the intracellular level through mechanisms that are being studied, and not only on the serotonin system.
If an anxiety disorder were caused by an excess of serotonin, by introducing a substance (SSRI) into the body that essentially ensures that there is a greater supply of serotonin, there would be no worsening of anxiety
. worsening of anxiety is also possible, so during the first weeks of therapy the picture must be carefully monitored, often the strategy of associating additional drugs to cover such eventual symptoms, it is sometimes necessary that the therapy is set in the hospitalization conditions.
If SSRIs act on blocking the reuptake by the neuron that secretes the serotonin, then the problem would not be that the neurons reuptake more serotonin than they should
. This is an interesting hypothesis. It concerns the functioning of the “re-uptake” (serotonin transporter within neurons: SERT). The genetic alterations of this protein have been related to various mental disorders, while the milder alterations – to the anxious traits of character. These hypotheses are still being studied. The alteration of this protein would however involve more complex phenomena that do not concern only serotonin, but the development of the whole organism.
Reasoning in this way, ex-juvantibus (starting from the benefit and the characteristics of the drugs), the main classical theories on the biological substrate of mental illnesses have also been postulated, but this strategy has the limit of proceeding according to the inductive method: a observation is potentially generalized to all cases, but in relation it explains only some of these. However, at least in some cases it can be valid.
If there is an automatic re-uptake of serotonin (a kind of block in case it is produced in excess), the usual advice of “the sun increases serotonin”, chocolate, music – ditto etc … would be useless
Chocolate does not contain serotonin, but contains substances from the family of amphetamines (phenylethylamine) which stimulate its production and block reuptake, and other stimulating substances (for example: caffeine, theobromine) which improve mood in a other way, and to add also the energetic and stimulating effect of calories. The use of chocolate as an antidepressant would have its limits, however, because the stimulants it contains can develop addiction.
Even in the case of the sun’s rays and, even more so, in the case of music, the effects on mood are mediated by several systems and are even more complex.
The light visible to the human eye, through a complex mechanism, blocks the production of melatonin (which is therefore produced in the dark). The production of melatonin consumes serotonin which is its precursor. Thus, when the eyes are exposed to visible sunlight, more serotonin remains unconsumed by this process and potentially available. The ultraviolet rays of the sun stimulate the production of melanins, the pigments to which the color and tan of the skin are due. The cells (melanocytes) that produce these pigments derive from the primary nervous system and to manufacture the pigment they use the same amino acid (tyrosine) whose partial elaboration is also used for the synthesis of dopamine (another substance involved in the regulation of mood and anxiety ). The skin is rich in other cells and nerve fibers that are able to produce serotonin in response to stimulation of various types (mechanical, thermal, solar). However, what is the relevance of the substances produced in the skin to the central nervous system cannot be said with certainty, but ultraviolet light also stimulates the production of vitamin D in the skin and hormones. Ultraviolet therapy has been shown to be effective in some forms of anxiety and depression, particularly in the seasonal forms, but it is less studied in the other forms. On the correlations between the sun and mood, see also the previous article (https://www.medicitalia.it/blog/psichiatria/1208-salute-psichica-d-estate.html).
The transmission of signals between neurons using serotonin is involved in a multitude of processes. One of these is the analysis of auditory stimuli, of the balance of the body and the integration of these with other stimuli. For several years it has been shown that plasma levels of serotonin are affected by vibrations and noises of a certain frequency. Even the sound frequencies used in discos can influence the levels of serotonin, in synergy with amphetamines, while some modern studies and devices, using sound stimulation at frequencies that stimulate the secretion of serotonin, propose to favor in this way the state of greater Welfare. Being confident and without discrediting such research, However, it is not yet clear enough whether this serotonergic reactivity is associated with the improvement of anxiety or vice versa and how important these effects may have on the functioning of the nervous system as a whole. On the other hand, the effects of music on the psyche are certainly not mediated only by serotonin.
It should be borne in mind that the association between serotonin and the treatment of anxiety and depression, first provided by science, then became a cultural heritage independent of scientific developments, a concept with a life of its own, in analogy with adrenaline (think of the phrases “having adrenaline in my blood” or “my adrenaline has risen” which convey emotional meanings in the contexts of speech that may not be related to neurophysiology at all). Thus, serotonin is also a “good mood hormone” in the popular mentality. It remains to be hoped that over time we will have become more aware of the symbolism that contains this statement and will be more reflective before trying to treat serotonin as something that is actually good or bad in itself. The problem in most cases is not serotoniin itself, but the system of which it is a part.
It is known that the precurson of serotonin is tryptophan, an amino acid that the human body does not produce and that must be taken with food (therefore called an “essential” amino acid). There may be the presence of mental disorders due to an actual lack of tryptophan (and therefore of serotonin) due to an incorrect diet and not to a defect in its secretion or recaptation
Psychic illnesses in which serotonin is involved are quite frequent even among people who follow a balanced diet. Indeed, in the “Western world” and in the “wealthy” countries, where, on average, deficiency diseases are less frequent, mental illnesses are on the increase. Perhaps because not everything depends on primitively biological factors, but also a lot on social factors which in a species like the human one are very influential on the degree of evidence of the experiences and behaviors we have the potential to manifest (we are kindly and expertly “programmed “,” susceptible “).
However, tryptophan deficiency impairs not only the serotonin system, but also other very important processes, and when it takes place (for example, in populations that follow a particularly restricted diet, based exclusively on only certain cereals, prepared only for in a certain way, like the famous corn: in the past also in Europe), the deficiency can actually manifest itself with quite severe psychic symptoms (comparison of which, however, with mood and anxiety diseases in the strict and questionable sense) and also with other symptoms, not psychic: all determined by a serious impairment of the metabolism as a whole. This disease is known under the name of “pellagra” (because it causes the skin to become sour).
Tryptophan is in any case present in most proteins, including proteins of vegetable origin, and also in corn, in which it is available, if corn is properly processed. Today and in our society, tryptophan deficiency is more probable in the context of multiple food deficiencies determined by the pathological lifestyle, upstream of which a mental illness is often already present, for example a severe depressive state (in which the instincts of survival are altered, and the person can not eat), a state of closure in psychotic disorders, cognitive deterioration, dependence on alcohol or other substances, or even in very advanced age without a psychic disorder but with the para-physiological reduction of the instincts of thirst and hunger.
In this case (of mental disorders due to an actual lack of tryptophan (and therefore of serotonin due to an incorrect diet), taking SSRIs, what would happen
In such cases, actually, therapy with antidepressant drugs alone will most likely not be effective, because, to function, it needs a minimum sufficient degree of integrity of the organism, in particular, the integrity of the functioning of neuronal cells and the presence, in sufficient quantities, of neurotransmitters (not only serotonin, but also others) Therefore, in such cases it is first necessary to put the organism in order in its basic functions, to correct the deficiencies with the general medical approach, and often to do so the conditions of hospitalization are necessary.
The possible prescription of antidepressant drugs (and all remedies) in such conditions must be well monitored also from the point of view of the potential risks of their use, because the body’s ability to metabolise can also be reduced, eliminating in time the drugs and their metabolites, whose possible accumulation “in the streets” of the organism and “in the queue” to metabolize can complicate the situation. In the conditions of deficiency, the serotonin receptors can also develop a pathological hypersensitivity, while on the other hand, in the multi-deficiency state, the production deficit of the receptors or other anomalies is also possible, with not always predictable responses to antidepressants or other psychotropic drugs. Antidepressants, however, they have been irreplaceable in many of these cases, where, behind the “organic” aspect, the depression was almost unrecognizable or “passed to the second floor”. Therefore, as always, the “eye” of an expert is necessary in the evaluation of the clinical picture and in the choice of therapy.
Some insights.
On the history and mechanism of action of SSRIs:
https://www.medicitalia.it/minforma/psichiatria/243-depression-cosa-sono-la-serotonina-e-gli-ssri.html
http: // www. psychonline.it/prodotto_servizio/psicofarmaci_psicologo.htm
https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor
http://www.sciencedirect.com/science/article/pii/0166432896000927
Serotonin and music:
http: // www .musica-Spirito.it / music-2 / music-science / the-technology-of-binaural-beats /
https://www.ncbi.nlm.nih.gov/pubmed/10550905
https: //www.ncbi. nlm.nih.gov/pubmed/2074031
https://www.ncbi.nlm.nih.gov/pubmed/10941989
https://www.ncbi.nlm.nih.gov/pubmed/20515664
https://www.ncbi.nlm.nih.gov/pubmed/18722516
