Markers of Reduced Serotonergic Activity

Looking ahead, we will say that, in the group average of all markers of reduced serotonergic activity, an association is found with the socionic poles of process (rightness), constructivism, Questimity, foresight, merriness, negativism, strategy, and irrationality, and as a tendency also with ethics and intuition. The process pole makes the largest weighted contribution to the variance (52%). The most “antiserotonergic” function is Qi. The most “serotonergic” are Te and Di. The most “antiserotonergic” type is EIE (followed by ILE and ILI). The most “serotonergic” type is LIE (followed by IEE).

Serotonin is one of the most evolutionarily ancient modulators of metabolism and information processes in all living organisms (including even plants). Science currently counts 13 varieties of serotonin receptors alone in humans (that is, varieties of peptide “keyholes” on cells through which serotonin, as well as agonists and antagonists with similar effects, can influence a cell, including neurons, by changing its metabolism). Quite roughly, serotonin receptors are divided into 7 principal types, of which 6 are metabotropic and one is ionotropic (see the attached table). Most receptor types are each further divided into several subtypes, often differing substantially in function and properties.

The principal markers to be considered below, associated with the role of serotonin in regulating mental and physiological processes, are as follows:

• influence on pain sensitivity (serotonin reduces pain sensitivity)

• influence on thermoregulation and cold sensitivity (serotonin increases energy release in adipose tissue and reduces cold sensitivity)

• influence on hunger and appetite (serotonin, by intervening in the functional chains of a number of signaling peptides, suppresses hunger)

• influence on lipophilicity - predisposition to obesity (serotonin counteracts lipophilicity)

• influence on sweating associated with lipophilicity (serotonin is negatively correlated with sweating)

• influence on stress resistance and production of stress hormones (serotonin reduces cortisol release)

• influence on regulation of insulin and glucose levels (serotonin stimulates insulin and lowers glucose levels)

• influence on mood, including depression and anxiety (serotonin reduces depression and partially reduces anxiety)

• influence on explosiveness, impulsive outbursts of anger (serotonin reduces explosiveness)

• influence on insomnia (serotonin, being a precursor of the sleep-onset hormone melatonin, promotes normal rapid falling asleep)

• influence on memory (mainly negative on the part of serotonin)

• influence on cognitive thought processes (inhibition predominates on the part of serotonin)

• influence on the balance of activity of the visual and auditory analyzers (serotonin favors the visual analyzer more and rather hinders the auditory one)

• influence on physical activity (serotonin increases predisposition to physical activity)

• influence on predisposition to addictions, dependencies (serotonin reduces dependencies)

• influence on attitudes toward people (serotonin, by provoking oxytocin release, generally increases the level of empathy and trustfulness toward people)

• influence on bone formation (high peripheral serotonin, including intestinal serotonin, together with high cortisol, impedes bone formation and promotes osteoporosis and bone fragility)

• influence on nausea (through its 5-HT3 receptor, serotonin intensifies nausea and vomiting reactions)

• peripheral influence on the intestine (serotonin stimulates intestinal peristalsis and motility)

• peripheral influence on local inflammatory reactions (together with histamine, peripheral serotonin intensifies inflammatory reactions)

HIGH LIPOPHILICITY, - INCLUDING SLOW ONSET OF SATIETY FROM HUNGER, A TENDENCY TO GAIN WEIGHT (even with restrictions on food intake) - a marker of reduced serotonin.

1. I have troublesome problems with excess weight. 0.97

2. I have some tendency toward obesity. 0.90

3. My weight is above normal. 0.87

4. I have an excessively strong attraction to food - even when I have eaten recently, I often think about food again. 0.85

5. My increased appetite is a problem for me; soon after eating I feel hungry again. 0.83

6. I overeat. 0.81

7. I have a predisposition to fat deposition under the skin. 0.73

8. I usually eat with a certain greediness. 0.72

9. I often overeat because once I begin eating, satiety does not come soon - I eat and eat and cannot stop. 0.70

10. I can be greedy with food. 0.69

11. I eat pork fat fairly often (I like it). 0.63

12. I have a tendency toward corpulence. 0.60

13. As a rule, I finish my portion on the plate faster than the other people eating at the table. 0.56

14. I chew food quickly, with my jaws moving back and forth rapidly. 0.55

15. My body weight is unstable. 0.52

16. I have a tendency to accumulate excess fat on my body. 0.52

17. My neck is rather thick than thin (compared with peers of my sex). 0.52

18. Apparently I have a natural tendency toward excessive fat deposition. 0.44

19. I tend more toward thinness than corpulence. -0.93

20. My body weight is below the norm for my height. -0.89

21. My weight is somewhat below the norm for my height and age. -0.82

22. I am a “lean” person; there is no excess fat in my body and there never has been (if you are over 45 years old, assess this on the basis of your younger age - how it was then). -0.66

23. Although I eat normally, I am still thin - food just does not seem to put weight on me. -0.64

24. I do not consume butter and fats in food at all, or consume very little. -0.60

25. I do not have a single fold of fat on my abdomen (in general, I have a lot of muscle and little fat under the skin, so the skin on my abdomen can be pinched). -0.42

26. I have a normal weight corresponding to my height - neither above nor below normal, neither corpulent nor thin. -0.38

Central and peripheral serotonin (5-HT) acts on several targets at once (the CNS, liver, pancreas, and fat deposits), regulating metabolic homeostasis and ultimately reducing predisposition to obesity.

5-HT in the central nervous system acts on multiple nodes of the neuraxis (the hypothalamus, brainstem, and spinal cord), regulating satiety, hepatic glucose uptake, and adaptation to cold. Overall, through effects on its 5-HT-2C and 5-HT-1B receptors, serotonin suppresses hunger, increases hepatic glucose uptake, stimulates insulin in the blood, reduces release of stress hormones (cortisol – which in turn promotes obesity) and decreases the metabolic intensity of stress reactions, increases heat production by adipose tissue, and thereby improves adaptation to cold.

Thus, brain serotonin acts on central melanocortin neurons, suppressing food intake. Melanocortin receptor neurons (MC 3/4 R) integrate signals from two reciprocal populations of neurons within the arcuate nucleus in order to promote satiety. Activation of the serotonin 5-HT 2c receptor increases the activity of anorexigenic proopiomelanocortin (POMC) neurons, thereby suppressing hunger, whereas activation of the serotonin 5-HT 1B receptor inhibits orexigenic NPY / AgRP neurons – which also suppresses hunger. Thus, serotonin suppresses hunger through action in the brain on two serotonin receptors at once - 5-HT-2C and 5-HT-1B.

Serotonin in the pancreas stimulates insulin secretion and suppresses glucagon secretion (which raises blood glucose levels).

Pancreatic islets, or islets of Langerhans, contain endocrine cells that secrete hormones. The two principal endocrine cells of the pancreatic islets are beta cells, which secrete insulin, and alpha cells, which secrete glucagon. In the fed state, insulin suppresses endogenous glucose production and stimulates glucose uptake and its conversion into glycogen and lipids. Conversely, glucagon increases fasting blood glucose levels by stimulating glycogenolysis and gluconeogenesis. Insulin also acts on alpha cells, suppressing glucagon secretion (Cooperberg and Cryer, 2010). In addition to reducing food intake, enhancement of central 5-HT signaling also improves glucose homeostasis, which likewise counteracts obesity, - thus, treatment with fenfluramine or meta-chlorophenylpiperazine (mCPP, a 5-HT 1B / 2C receptor agonist) improves glucose tolerance and increases insulin sensitivity (Storlien et al. , 1989 ; Zhou et al., 2007 ). Locally synthesized 5-HT in the pancreas serves as an autocrine signal supporting normal insulin secretion (Sumara et al., 2012).

In addition to regulating insulin secretion, there is evidence that 5-HT also regulates glucagon secretion (Marco et al., 1977 ; Adeghate et al., 1999 ). For example, human islet beta cells have been reported to release physiological levels of 5-HT in response to glucose (Almaca et al., 2016 ). The release of 5-HT significantly reduces glucagon secretion, and this effect is mediated by the 5-HT 1F receptor (coupled to G i / o ) on alpha cells.

Thermoregulation

Thermogenesis through mitochondrial uncoupling occurs primarily in brown adipose tissue (BAT) and in beige adipocytes, a type of thermogenic adipocyte that appears in subcutaneous white adipose tissue (WAT) during prolonged exposure to cold (Cohen and Spiegelman, 2015 ). Adaptive thermogenesis has recently attracted broad attention as a potential therapy for combating obesity by increasing energy expenditure. Central 5-HT apparently promotes thermogenesis, because pharmacological or genetic depletion of central 5-HT has been found to impair thermogenic adaptation to cold (Fuller et al., 1987 ; Alenina et al., 2009 ; Hodges et al., 2011 ; Cerpa et al., 2014 ; McGlashon et al., 2015). For example, mice with central 5-HT depletion have reduced adaptation to cold, reduced thermogenic BAT function, and reduced recruitment of beige adipocytes (Alenina et al., 2009 ; Hodges et al., 2011 ; Cerpa et al., 2014 ; McGlashon et al., 2015 ). Central 5-HT apparently increases thermogenic function of BAT and beige adipocytes by modulating sympathetic outflow to these tissues. Taken together, these data suggest that inputs from central 5-HT pathways play an important role in adaptation to cold through sympathetic activation of thermogenic adipose tissue.

Thus, a high serotonin level counteracts obesity in many ways at once. By suppressing hunger, increasing insulin levels in the blood and lowering glucose levels, reducing levels of stress hormones and their obesity-provoking effects, and increasing heat production.

Accordingly, a low serotonin level promotes hunger, but to an even greater extent - promotes obesity (additionally reducing insulin secretion, increasing blood glucose, and strengthening the negative obesity-provoking action of cortisol). Three serotonin receptors play the principal role in all these effects: 5-HT-2C, 5-HT-1B, and 5-HT-1F.

Main source of information:

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STRENGTH OF APPETITE, ATTRACTION TO FOOD, IMPATIENCE WITH FOOD (Possible biochemical agents that increase the feeling of hunger: the endocannabinoid anandamide, ghrelin, neuropeptide Y, agouti-related peptide AgRP, orexin, melanin-concentrating hormone (MCH) , galanin, growth-hormone-releasing factor GHRH, cocalcigenin (CGRP, calcitonin gene-related peptide), motilin, beta-endorphin, beta-casomorphin, nociceptin). In addition, low serotonin intensifies attraction to food, whereas high serotonin, by negatively modulating the action of a number of hunger peptides - in particular, neuropeptide Y - weakens manifestations of hunger.

Unlike the appetite scale considered a few days ago, here we tried to eliminate all those questionnaire items that, in the former “large” appetite scale, appealed not to the feeling of hunger and greediness for food itself but rather to hedonic pleasure from food – we do not need such items here, because this hedonic factor has a different, strongly distinct nature and is based rather on the dopamine reinforcement center and the frontal cortex interacting with it. Let us see to what extent the scale under consideration succeeded in focusing only on the functioning of the hypothalamic hunger center.

1. I have an excessively strong attraction to food - even when I have eaten recently, I often think about food again. 0.81

2. I overeat. 0.79

3. My appetite is increased, and I am especially drawn to sweet or fatty foods. 0.79

4. I usually eat with a certain greediness. 0.78

5. My increased appetite is a problem for me; soon after eating I feel hungry again. 0.77

6. I can be greedy with food. 0.72

7. I often overeat because once I begin eating, satiety does not come soon - I eat and eat and cannot stop. 0.70

8. I chew food quickly, with my jaws moving back and forth rapidly. 0.57

9. During tasty meals, it often happens that I both want to and need to stop, but simply cannot. 0.49

10. As a rule, I finish my portion on the plate faster than the other people eating at the table. 0.35

11. I usually eat very little or simply out of obligation - I am rarely drawn to food. -0.91

12. Food as a rule does not arouse much appetite in me even while I am eating - food usually leaves me indifferent. I do not feel the “sweetness of anticipation” when beginning to eat. -0.85

13. I have a poor appetite and more often eat “out of obligation.” -0.83

14. I rarely feel hunger, even if I have not eaten all day. -0.80

15. I am rarely drawn to food; a feeling of hunger is not characteristic of me. -0.77

16. Food rarely arouses my appetite; often it seems almost tasteless to me. -0.75

Attraction to food (a mixture of the factor of insatiability of hunger and the factor of appetite) can be regarded as another marker of reduced central serotonin, which suppresses hunger through its 5-HT-2C and 5-HT-1B receptors. According to some data, agonists of 5-HT1A receptors may also participate in appetite suppression, in addition to the above-mentioned 5-HT-2C and 5-HT-1B receptors.

However, compared with the general predisposition to obesity (the lipophilicity considered in the previous post), many other factors besides serotonin level may play an even greater role in the case of effects on appetite.

What, apart from serotonin as the “supreme overseer,” regulates hunger? At the lower links of metabolic regulation?

This was described well in 2011 by the well-known science popularizer and psychiatrist who published in LiveJournal under the nickname Stelazin (stelazin.livejournal.com/92911.html ). We will not try to be original; we will simply quote him:

“Cells of the gastric mucosa produce a neutral protein that is broken down into 2 active peptides that are functional opposites of each other, - ghrelin and obestatin. Ghrelin was discovered in 1999, obestatin in 2004, but they have only been taken seriously for the last 5 years. They are interesting because their actions are directly opposite, although they are encoded by one gene. When the digestive system has nothing to do, ghrelin is released into the blood; when the intestine is digesting something, - obestatin is released. Accordingly, - ghrelin sharpens appetite, obestatin suppresses it. Both do this by acting on the feeding center. The feeding center is, first and foremost, - the arcuate nucleus of the hypothalamus.

Neurons of this center constantly produce substances responsible for the subjective experience of hunger; there are several of them, primarily - neuropeptide Y and anandamide (an endogenous cannabinoid, which is exactly why cannabis intoxication gives you the munchies). These peptides are blocked by leptin; thus, leptin suppresses the feeling of hunger.

Leptin is produced by adipose tissue and is needed for many things; in particular, - it participates in thrombus formation and suppresses insulin production, so in people with obesity the risks of thrombosis and diabetes mellitus rise sharply. It also, as stated above, suppresses hunger, so theoretically, - more fat means lower appetite. This is biologically reasonable, - the animal is eating well, the animal has become fat, there is a reserve of fat, - the satiety center can loosen the reins and stop driving it so intensely to search for food.

Then the information is sent through the ventral thalamic nuclei to the insula. The insular cortex is the final stop; it is the highest cortical control center. Its principal job is recognizing tastes and determining the suitability of food. It has been shown that the insula responds to taste intensity and does not respond to its subjective “pleasantness.” It also participates in forming the emotion of disgust. In other words, it deals with fairly functional matters; tasty treats and excesses are not among its tasks.

This is a very rough scheme; in reality everything there is much more complex and tangled. Cholecystokinin and insulin are also involved, as are amino acids/lipids/carbohydrates directly; and in the thalamic nuclei there are 2 different functional groups of neurons producing the peptides NPY/AGRP (which excite hunger) and POMC/CAR (which suppress hunger).

And where is the place for tasty treats and excesses? That is already in the interaction cycle of the prefrontal cortex and the dopamine reinforcement center in the basal ganglia of the brain – the globus pallidus and nucleus accumbens. The pathways of taste recognition and satiety pass through the Ventral tegmental area (a basic node of neurotransmitter networks), from where the VTA directs signals to the ventral pallidum, then to the Nucleus accumbens (2 centers controlling hedonic feeling, the so-called hedonic hotspots), then the information passes to the cortex, - anterior cingulate, insular, orbitofrontal, then to the ventromedial prefrontal area and back to the hedonic hotspots. The cycle closes.

The nuclei of the feeding center can be inhibited, stimulated, the substances they produce can be blocked; the situation can be influenced in different ways, but in the baseline state, - they continuously produce and produce “hunger neuropeptides.” Different states, physiological and pathological, different medicinal or narcotic substances, mental practices and active supplements, - can affect the subjective feeling of hunger in different ways, dampening it, sharpening it, or distorting it. Because there is something to act upon; we cannot influence satiety in such diverse ways, because it is not an independent experience. It is the organism’s reaction to the absence of hunger. Hunger is primary. It is a little drill in the medulla oblongata that by default is drilling all the time; we can only temporarily shut its mouth with another portion of food. It is not a toggle switch “hungry-full.” It is a button. Press the button down with a portion of calories, - the drill falls silent. The calories are utilized by the body, - the button springs back up, - the arcuate nucleus starts drilling again. Initially, - there is nothing tasty, there is only what is edible. There is no pleasure from food; all of that is layered on top. There is only the eternal hungry howl and a way to muffle that howl for a little while so that it does not drive you mad. The best reward, - is a temporary cessation of punishment, - Mother Nature loves such tricks.

Special “satiety centers” are simply evolutionarily useless. Food resources are always limited. And if suddenly there is more food than an animal is capable of obtaining, the species evolves toward larger size until it again runs up against the energy ceiling of the ecosystem. For example, in the climatically favorable conditions of the Eocene, 20-ton herbivorous mammals and correspondingly sized predators appeared in this way. Who could have imagined that someday a species would appear that, in its present configuration, has unlimited access to food. 150 years ago we ourselves could not have imagined such a thing. Therefore humans have no mechanisms protecting them from overeating. No one does. Not a single pig and not a single broiler chicken has ever said, “That’s all, thank you, I think I’ve had enough.” Who could have known that it might become useful? Yummy food with mayo, - is a biologically incredible event.”

What is especially important for us in the long but interesting quotation above? A multitude of substantial ancient subcortical structures work for the hunger center, using many different peptides to excite hunger. However, wherever subcortical centers provide instincts and behavioral motivation – there we will always encounter strong sensing. Therefore, in the case of increased appetite, a simple sensing profile will necessarily be superimposed on our low-serotonin profile, reflecting the intensified, active functioning of numerous subcortical structures, beginning with the nuclei of the hypothalamus.

This is exactly what we see in the resulting socionic profile of the property, where “process” clearly jumps upward because of reduced serotonin, “Questimity” reflects the involvement in appetite of the insular cortex apparatus, which evaluates the intensity of taste sensations and rejects health-threatening “poisonous” ones, while everything else (or almost everything else, with sensing at the forefront) – is the resultant of the sensing influences of numerous subcortical structures and their peptides working for the Hunger Center.

Absence of symptoms of bruxism (grinding the teeth in sleep) and trismus (convulsive contraction of the jaw muscles). The presence of such symptoms indicates significantly elevated serotonin, whereas their absence indicates, accordingly, a not-high (normal) level of serotonergic activity.

1. Often, when thinking about something, I mechanically “click” my teeth - that is, tap them or lightly rub them against one another, as if chewing. -0.81

2. Often, when thinking about something neutral, I mechanically clench my teeth or rub them against each other, as if checking my bite - I have this habit. -0.75

3. Even when I am chewing nothing and there is absolutely nothing in my mouth, for example when I am simply working at a computer, I have a mechanical habit of moving my jaws - periodically tapping my teeth together or lightly rubbing them against each other, as though constantly checking my bite. -0.77

4. I am told that in my sleep I sometimes grind my teeth, tap them together, or rub them against each other with a scraping sound (I am told this has happened at least once). -0.68

5. Sometimes my jaw contracts as if in a cramp. -0.63

6. Sometimes I feel that my jaw muscles are overstrained - as though they are being contracted by a spasm. -0.66

7. Sometimes the muscles of my jaws refuse to obey and contract convulsively. -0.59

8. Sometimes the muscles around my jaw and mouth tense so strongly that speaking and chewing become difficult. -0.57

9. Sometimes I grind (gnash) my teeth in my sleep (5 - if it still happens now, 4 - if it happened at some time, 1 - if you are unaware of doing this). -0.48

10. I often make movements with my jaws as though chewing even outside of eating. -0.48

11. How many pieces of chewing gum do you use on average per day? 1) None 2) One or two 3) Three to five 4) Six to nine 5) Ten or more -0.37

12. Sometimes my jaws contract as though from a muscle spasm, involuntarily clenching my teeth. -0.34

13. Sometimes my jaw muscles are tensely contracted (independently of my will), although my mood at the time is bright and good. -0.32

Bruxism and trismus are rare symptoms, usually appearing only at sharply elevated concentrations of serotonin (for example, in overdoses of drugs that increase serotonin content in the neuronal synaptic cleft). Therefore the socionic profiles corresponding to the absence of these symptoms are not very contrasting (and thus not very reliable), but they nevertheless show some tendencies. Of particular significance to us is the association of the process pole with the particular rarity of symptoms of bruxism and trismus – another indication of an association of “process” with low serotonin and “result” with high serotonin.

The indication in the resulting socionic profile of an alleged association of high serotonin with intuition and negativism already appears doubtful (and possibly artifactual), but the indication of an association of serotonin (by the bruxism marker) with logic, the result pole, Declatimity, carefreeness, and seriousness is unsurprising.

PREDISPOSITION TO DEPRESSIVE STATES

1. I am prone to depression. 0.97

2. I am often sad. 0.94

3. A bad mood arises easily in me and may persist for several days. 0.93

4. Repetitive negative thoughts often come to mind. 0.93

5. Something always casts a shadow over my joy. 0.93

6. I periodically have severe depressive states in which I do not want to live. 0.93

7. I have problems because of poor sleep, insomnia, and reduced productivity in my activities. 0.92

8. I often cannot get out of a bad mood for a long time. 0.91

9. Almost every week something happens about which I later torment myself with belated regrets. 0.91

10. I retain memories of unpleasant events for a long time. 0.90

11. I am always at least slightly dissatisfied with something. 0.90

12. I am often troubled by my gloominess, anxiety, irritability, as well as by my frequent tendency to become “stuck” on some thoughts or on some unpleasant state. 0.89

13. My life is filled with much suffering. 0.89

14. I am often in a depressive, minor-key mood. 0.89

15. I often fall into despondency. 0.89

16. I sometimes have a feeling of inferiority and depression that I carefully conceal from others - because of thoughts that I do not meet the high demands I myself place on my life. 0.88

17. For some time now, without any apparent reason, I have felt chronically tired and as though “worn out.” 0.88

18. My general sense of the world is rather somewhat sad than lively and cheerful. 0.88

19. I feel hopelessness or helplessness. 0.87

20. I have thoughts of self-destruction. 0.87

21. A bad mood predominates in me. 0.87

22. I foresee only frightening events in the future. 0.87

23. I often feel depressed and passive. 0.86

24. More than half the time, pessimistic and depressive thoughts predominate in me. 0.86

25. I often feel deceived, disadvantaged, and offended. 0.86

26. I have a sleep disorder (I sleep too much or too little). 0.86

27. I often feel annoyed and disappointed. 0.85

28. I often feel sad. 0.85

29. I often feel dissatisfaction or boredom. 0.85

30. I often cannot get out of an oppressive-anxious state for a long time. 0.84

31. I often have a depressed, depressive mood without any apparent reason. 0.84

32. I feel apathy, a lack of motivation to act. 0.83

33. Troubles can provoke episodic suicidal thoughts in me with an aggressive attitude toward myself, when I “want to kill myself.” 0.82

34. I have suicidal thoughts. 0.82

35. I have dark thoughts, for example about murder or suicide. 0.81

36. I have had suicidal thoughts several times in my life. 0.75

37. At times I think about death, turning this subject over in my thoughts in different ways. 0.72

38. Toward the end of a line in my handwriting, words usually begin to “curve” downward, so that the line descends at the end, bending toward the bottom of the page (check this). 0.44

39. I easily disregard past unpleasant events and live in the present, feeling calm confidence in tomorrow and in my future in general. -0.93

40. I am more optimistic than most people. -0.90

41. My presence in a group almost always stimulates other people’s initiative. -0.86

42. I do not remain stuck on anything unpleasant for long and can unite people through my optimism. -0.85

43. It is true that I have never had suicidal thoughts directed toward suicide that lasted for any significant length of time - at least for an hour - even thoughts that later pass and do not end in any life-threatening action. -0.79

44. I very rarely experience such feelings as worry, fear, and sadness. -0.78

45. I am quite satisfied with life. -0.77

It is considered that the neurochemical basis underlying the manifestations of depressive disorders consists mainly in disturbances in neurotransmitter systems such as the serotonergic, noradrenergic, and dopaminergic systems (Bardshtein L. M., 2004; Tabaeva G. R., 2008; Tyuvina N. A., 2009; Praagvan H., 2004; Aberg N. D., 2006; Duman R., 2006; Mossner R., 2007; Hamon M., 2007; Duncan L., 2009).

Predisposition to depressive states is, of course, caused not only by dysfunctions in the brain’s serotonergic system. There are many studies demonstrating contributions to the development of depressive disorders from other monoaminergic transmitters, as well as more specific regulators at the level of a number of peptides and agents causing inflammation of neurons and neuroglia. However, the role of deficient serotonergic tone in the genesis of depression is still regarded in the scientific literature as one of the leading ones. At least, methods currently used in psychiatry to treat depressive disorders remain predominantly directed at this target and are intended to raise the patient’s level of serotonergic activity. Serotonergic antidepressants (SSRIs), tricyclic antidepressants, MAO inhibitors – all drugs used in medicine to treat depression raise serotonin concentration (both free serotonin and specifically serotonin in the synaptic cleft).

Approximately 6 % of men and 18 % of women suffer from depressive disorder (Blazer D. G., 2000), while the lifetime risk of developing depression is 7—12 % for men and 20—25 % for women. The sex differences here are not accidental and repeat the sex differences in serotonergic activity between men and women (men have a higher serotonin level).

The brain’s serotonergic system is directly related to the formation of depressive states and participates in controlling the activity of other transmitter systems, primarily the GABAergic and monoaminergic systems, which are also related to correction of aggressive and impulsive behavior. The results of numerous studies indicate that a deficit of serotonergic mediation is an important pathophysiological mechanism of depression.

Depression is associated both with a direct decrease in serotonin concentration in the brain and with the activity of other components of the serotonergic system (serotonin receptors, the serotonin transporter, etc.), as convincingly demonstrated by the results of using various pharmacological agents (van Praag H. M., 1998). Direct correlational relationships have been identified between the content of serotonin and its metabolites in cerebrospinal fluid and blood plasma, and the validity of using indices of the peripheral humoral component of the serotonergic system as a model for studying its synaptic (central) component has also been demonstrated (Celada P., Artigas F., 1993). A reduced serotonin level is highly correlated with depressive disorders of different degrees of severity.

It is considered that the principal role in suppressing symptoms of depression is played by agonistic action on serotonin receptors in the CNS of the 5-HT 1A subtype. The same action also works against anxiety and is used in treating anxiety disorders. Stimulation of serotonin receptors of other subtypes also works against depression: 5-HT2A, 5-HT2C, 5-HT4, and 5-HT6.

Bokhan N. A. Ivanova S. A., Levchuk L. A. The Serotonin System in the Modulation of Depressive and Aggressive Behavior. - Tomsk: Ivan Fyodorov Publishing House, 2013. 102 pp.

www.mental-health.ru/files/edu/…

Celada, P. Plasma 5-hydroxyindoleacetic acid as an indicator of monoamine oxidase-A inhibition in rat brain and peripheral tissues / P. Celada, F. Artigas // J. Neurochem. – 1993. – Vol. 61. – № 6. – P. 2191—2198.

Van Praag, H. M. Depression, Anxiety Disorders, Aggression: Attempts to Untangle the Gordian Knot / H. M. Van Praag // Mediografiya. – 1998. – Vol. 20, № 2. – P. 27—35.

HIGH LEVEL OF NEUROTICISM AND ANXIETY

1. I experience nervousness and anxiety. 0.96

2. I usually find it difficult to distract myself from some disappointment or distress. 0.95

3. I am a nervous person. 0.94

4. I frequently have anxious states and moods, including during the past week. 0.93

5. I have chronic anxiety. 0.93

6. I often experience anxiety and worry. 0.93

7. Negative emotions can rapidly “wind themselves up” in me even over minor matters. 0.93

8. Severe stress (for example, in the form of intense worry or nervous tension) as a rule leads me to depression during the following several days, when I do not want to do anything at all and life itself seems meaningless. 0.92

9. I am often agitated or irritated. 0.92

10. I easily fall into a state of stress. 0.92

11. I often have an anxious-irritable mood. 0.90

12. I worry a great deal, often without reason. 0.90

13. I am often nervous. 0.90

14. I often feel anxious and tense. 0.89

15. I have had panic attacks in my life, when I was extremely agitated and simply could not find a place for myself. 0.89

16. Over the past month I have more than once had to experience feelings of grief, despondency, sadness, melancholy, depression, almost despair. 0.89

17. Even very weak external stimuli can deprive me of peace of mind. 0.88

18. Sometimes I am forced to take anti-anxiety medications (tranquilizers) to relieve groundless anxiety that interferes with me. 0.88

19. I often enter an agitated-irritable state. 0.87

20. I often have acute reactions of disappointment and dissatisfaction. 0.86

21. I regularly (at least once a week) have excessively anxious states without a compelling reason. 0.86

22. My memory contains old scenes of offenses inflicted on me that still evoke concealed anger in me. 0.84

23. I often experience fear or anxiety. 0.84

24. I have some frequent and intrusive memories. 0.84

25. Many things seem disgusting to me and affect me strongly. 0.84

26. Sometimes, when swimming, I am afraid of drowning. 0.83

27. I am a restless person. 0.83

28. How often do you remember that in the past - distant or recent - you said or did something “wrong,” awkward for yourself or hurtful to others? 1) Never 2) On average once a month 3) Once a week 4) Almost daily 5) Several times a day 0.81

29. Frequently recurring attacks of anxiety are usual for me. 0.81

30. In the evening in bed I sometimes find it difficult to fall asleep. 0.80

31. A high level of fearfulness and anxiety is usual for me. 0.80

32. I often have some kind of anxious thoughts. 0.79

33. I sometimes have a tic (twitching) of the facial muscles. 0.78

34. I have symptoms of excessive muscular tension (headaches, muscle pain, hand tremor). 0.75

35. I am often infuriated by all kinds of minor irritants and inconveniences that people present in the room are very good at creating for me. 0.69

36. I cannot relax. 0.68

37. I am easily irritated by offenses. 0.68

38. I often feel tired without any particular reason. 0.62

39. I sometimes have frequent urination, when I feel the need to go to the toilet “to urinate” too often. 0.56

40. Lately I both feel worse than before and become more tired than usual (if so, enter 5 or 4; if the opposite, enter 1 or 2; if there is nothing special, enter 3). 0.54

41. It is easier for me to retrieve some sharply unpleasant memory than to recall something pleasant. 0.40

42. I extremely rarely have reasons to worry and become nervous. -0.94

43. I am a person with little anxiety. -0.93

44. Any circling of unpleasant thoughts subsides very quickly in me; past offenses rapidly lose relevance, being replaced by a feeling of satisfied calm and confidence. -0.92

45. I remain calm, confident, and optimistic even in difficult situations. -0.92

46. I do not worry over trivialities. -0.91

47. It is true that I extremely rarely experience troubles that would disturb my emotional equilibrium. -0.86

48. It is true that fear of unemployment and misfortune is completely unlike me; I have never had and do not have these worries. -0.85

49. My rules are “everything is bullshit” and “do not get upset over bullshit.” -0.85

50. For a long time now (at least - many months), I have not known what disappointments or troubling problems are. -0.84

51. My strengths are strong nerves and unwavering self-control. -0.79

52. I fall asleep easily at night. -0.69

53. I know how to reduce emotional intensity quickly, to wind down and end a verbal quarrel quickly when it is no longer needed or becomes dangerous. -0.64

As in the case of depression, anxiety is associated, among other things, with reduced serotonin in the CNS. The principal role in suppressing symptoms of anxiety is played, in addition to stimulation of benzodiazepine receptors, by agonistic action on serotonin receptors in the CNS of the 5-HT 1A subtype.

Bokhan N. A. Ivanova S. A., Levchuk L. A. The Serotonin System in the Modulation of Depressive and Aggressive Behavior. - Tomsk: Ivan Fyodorov Publishing House, 2013. 102 pp.

ABUNDANCE OF DREAMS. Duration of the rapid-sleep phase (5-HT1A agonists minus)

(a marker of weak serotonergic activity)

Serotonin exerts its action in the CNS primarily through its most numerous and widespread receptors (both in the periphery and in the central nervous system), receptors of the 5-HT1A type.

As a brief introduction to the topic, the following should be emphasized. These receptors can be presynaptic, that is, located on the neuron “before the synapse” – in this case their activation by synaptic serotonin or other agonist substances leads to a reduction in serotonin release from the neuron into the synaptic cleft, that is, to a reduction in serotonergic activity. But receptors of the same type are also postsynaptic, that is, they are located after the synapse on the body of the next neuron in the chain, and in this case their excitation by serotonin from the synaptic cleft (released there by the preceding neuron in the chain) leads to excitation of the subsequent neuron, that is, to enhancement of serotonergic action and an increase in overall serotonergic activity.

At low concentrations of serotonin or another receptor agonist, the action of presynaptic 5-HT1A receptors predominates; through a negative-feedback mechanism, they exert an inhibitory effect on the transmitting neuron and ultimately stabilize serotonergic interneuronal transmission at a constant level (practically independent of the concentration of serotonin or another receptor-exciting agent in the synaptic cleft). But when concentrations of serotonin or another agonist of this receptor type rise strongly, their postsynaptic effect begins to predominate instead, ultimately enhancing serotonergic interneuronal transmission.

Therefore, in biology and medicine, all experiments involving activation of serotonin receptors are conventionally conducted in two variants - at low concentrations of the receptor-stimulating agonist and at high concentrations. In the first case, the effect is considered to be caused by activation of presynaptic receptors exerting an inhibitory effect on serotonergic transmission. In the second case, the identified effects are considered to be caused by activation of postsynaptic receptors that stimulate serotonergic interneuronal transmission.

Numerous studies of sleep structure (conducted mainly on rodents, rats, in which serotonin receptor functions differ little from the functions of these receptors in humans) have shown that activation of both presynaptic and postsynaptic serotonin receptors of the 5-HT1A type invariably leads to a reduction in the so-called REM phase within sleep structure (that is, the sleep phase with rapid eye movements under the eyelids – it is precisely in this phase that all mammals experience dreams).

This phase is also called “rapid sleep” - because unlike “slow,” or “delta sleep,” which is characterized by slow electrical oscillations (delta waves) on the brain electroencephalogram, during the REM phase rapid high-frequency oscillations (fast waves) predominate on the electroencephalogram. These “fast waves” of the electroencephalogram are precisely a marker that a person (or another mammalian animal) is experiencing a dream at that moment. In short, in practically all studies, “rapid sleep” was suppressed regardless of the administered dose of any 5-HT1A receptor agonist. This means that activation of both presynaptic and postsynaptic serotonin receptors of this type leads to a reduction in dream time within sleep structure.

The depth of slow-wave sleep (the kind without dreams) during activation of 5-HT1A receptors can change in different ways depending on which receptors (presynaptic or postsynaptic) were predominantly activated, although effects involving reduction of total sleep duration and deepening of sleep in its slow-wave phase generally predominate. However, the duration of the REM phase of sleep with dreams was invariably and significantly reduced under all experimental conditions.

The principal effects of serotonin on sleep structure identified in experimental studies (namely, from activation of its 5-HT1A receptors on neurons) are as follows:

1. Total sleep duration decreases, that is, the level of wakefulness increases.

2. The slow-wave phase of sleep (without dreams) usually deepens – the animal wakes less often.

3. The total duration and proportion within sleep structure of the REM phase of sleep (with dreams) steadily decreases.

4. The latency to onset of the REM phase increases (that is, the period from falling asleep to the first dreams).

5. Activation of another type of serotonin receptor, 5-HT7, conversely leads in mice to an INCREASE in the duration of the REM phase of sleep. However, receptors of this type are few in number and “do not determine the overall picture” - the general effects of serotonin are dominated by effects from activation of its most numerous 5-HT1A receptors.

6. However, directly in the raphe nuclei (where serotonin originates so that it can then be distributed throughout the brain via serotonergic terminals), the picture is different. Direct application of 5-HT1A agonists into the dorsal raphe nuclei of the rat brain leads not to a reduction but to an increase in the duration of the REM phase of their sleep. Why? The point is that in this region the serotonin-transmission-inhibiting effect of 5-HT1A receptors dominates, and increasing the concentration of serotonin or its agonists in this region leads, according to the principle of negative feedback, to a reduction in serotonin transport to specialized brain regions - including those directly controlling sleep structure. Leading sleep-structure researcher Monti J. M writes the following about this:

“Microdialysis perfusion of a selective 5-HT1A agonist into the dorsal Raphe nucleus, conversely, causes an increase in the rapid-sleep phase, while other sleep / wakefulness stages remain unchanged. The increase in the rapid-sleep phase is probably associated in this case with reduced neuronal serotonin (5-HT) activity and thus reduced 5-HT neurotransmission in the terminal projection area of serotonergic neurons, for example in the laterodorsal and pedunculopontine tegmental nuclei. Direct injection of a selective 5-HT1A agonist into the pedunculopontine tegmental nuclei reduces REM sleep, which is consistent with this hypothesis.”

Thus, here as well there is no contradiction with the general role of serotonin in reducing dreaming and reducing total sleep time.

All these complex data on sleep / wakefulness under the influence of 5-HT1A ligands indicate that activation of the 5-HT1A receptor generally increases overall wakefulness and reduces dream time.

Thus, serotonin, through its 5-HT1A-type receptors, suppresses dreaming, and THOSE PEOPLE WHO EXPERIENCE DREAMS MORE OFTEN THAN OTHERS (that is, who wake more often during the REM phase of sleep) are, as a rule, PEOPLE WITH REDUCED SEROTONERGIC ACTIVITY.

This is usually equivalent to a low concentration of serotonin in the synapses of neurons in their brain or reduced sensitivity of serotonin receptors on neuronal cell bodies (or equivalent to both simultaneously).

For more detail on studies and evidence of reduction in the total duration of REM sleep with dreaming under the action of serotonin or other selective agonists of its 5-HT1A receptors, as well as lengthening in this case of the latency period from falling asleep to the onset of the first REM phase of sleep and a general increase in wakefulness (reduction in total sleep duration), see here:

1. Monti J. M., Jantos H. Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat (English) // J Sleep Res : journal. — 1992. — Vol. 1, no. 3. — P. 169—175. — doi:10.1111/j.1365-2869.1992.tb00033.x. — PMID 10607047.

2. Marc Ansseau, William Pitchot, Antonio Gonzalez Moreno, Jacques Wauthy, Patrick Papart. Pilot study of flesinoxan, a 5-HT1A agonist, in major depression: Effects on sleep REM latency and body temperature (English) // Human Psychopharmacology: Clinical and Experimental : journal. — 2004. — Vol. 8, no. 4. — P. 279—283. — doi:10.1002/hup.470080407.

3. Monti JM, Jantos H, Silveira R, Reyes-Parada M, Scorza C, Prunell G. Depletion of brain serotonin by 5,7-DHT: effects on the 8-OH-DPAT-induced changes of sleep and waking in the rat. Psychopharmacology (Berl). 1994 Jun;115(1-2):273-7. doi: 10.1007/BF02244783.PMID: 7532312

4. Bjorvatn B, Ursin R. Changes in sleep and wakefulness following 5-HT1A ligands given systemically and locally in different brain regions. Rev Neurosci. 1998;9(4):265-73. doi: 10.1515/revneuro.1998.9.4.265.PMID: 9886141 Review.

5. Monti JM. Serotonin control of sleep-wake behavior. Sleep Med Rev. 2011 Aug;15(4):269-81. doi: 10.1016/j.smrv.2010.11.003. Epub 2011 Apr 2.PMID: 21459634 Review.

6. Monti JM, Jantos H, Catenaccio V, Xavier S.Blockade of the NMDA and AMPA/kainate receptors in the dorsal raphe nucleus prevents the 5-HT₃ receptor agonist m-chlorophenylbiguanide-induced suppression of REM sleep in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jul 1;35(5):1341-8. doi: 10.1016/j.pnpbp.2011.04.001. Epub 2011 Apr 13.PMID: 21514352

DREAM FREQUENCY SCALE (correlate of duration, that is, prolongation of the REM phase of sleep with dreams)

1. I see some kind of dreams almost every night. 0.96

2. I frequently have vivid, colorful dreams. 0.94

3. After waking at night during a dream, with my eyes open I continue for some time to see moving colored patterns against the walls or gradually dissolving figures from my dreams. 0.93

4. I see dreams almost every night. 0.92

5. I often have vivid dreams with an “adventure” plot. 0.92

6. I fairly often have colorful dreams with a fairy-tale, fantastic plot. 0.89

7. It happens that upon waking, after opening my eyes, for several seconds I continue to see images from my dream against objects in the surrounding environment. 0.88

8. Before falling asleep, with my eyes closed I often see synchronously changing colored ornaments, companies of cartoon little people marching in formation, etc. 0.86

9. I often dream about something. 0.83

10. I dream about something almost every night. 0.77

11. About once a month or more often, I wake at night because of an unpleasant dream. 0.66

12. I often wake at night because of some dreams. 0.64

13. After awakening from sleep, it sometimes happens that for several seconds, already with my eyes open, I still see before me a fairly vivid continuation of my dream, with the same or new characters. 0.32

14. Deep sleep without dreams is usual for me. -0.96

15. I see nighttime dreams very rarely or not at all. -0.88

16. I have even, deep, and restful sleep with rare or absent dreams. -0.84

As can be seen from the table of socionic profiles, the effects of low serotonin in this case had little effect on the increase of the process pole; however, high constructivism, Questimity, merriness, ethics, intuition, and irrationality appear unchanged - further fairly stable components of most markers of reduced serotonin.

PREDISPOSITION TO MIGRAINES, MIGRAINOUS PERSONALITY TYPE - the literature discusses two principal causes: reduced serotonin and elevated histamine, the action of which is partly reduced, again, to lowering serotonin concentration

Noise or ringing in the ears is a symptom that often accompanies the migrainous personality type and frequently precedes migraine attacks.

1. I sometimes feel noise in my ears. 0.80

2. I sometimes hear ringing in my ears (at least once a month) 0.78

3. At least once a week I have noise or ringing in my ears. 0.72

4. I have a migraine more often than once a month - a very intense pulsating headache of a sharply stabbing character (specifically pulsating or sharply stabbing, rather than evenly and continuously constricting), localized more on one side of the head. 0.70

5. I have a pulsating headache on one side of the head, radiating to the back of the head, usually arising in connection with bad weather - an increase in air temperature and humidity, increased cloudiness, etc. 0.69

6. Sometimes, when it is quiet around me, I perceive noise in my ears. 0.67

7. I have spasmodic headaches (migraines). 0.64

8. I get headaches fairly often - on average no less often than once a month. 0.61

9. I have headaches in my right temple associated with hunger - they occur if I skip lunch or forget to eat dinner. 0.57

10. I get headaches more often than once a month. 0.53

11. What has happened to you in your life? 1) Allergy 5) Migraines 3) Neither has occurred, or both have occurred 0.45

12. My head (in the temples) hurts extremely rarely or not at all. -0.61

MIGRAINE AS A CONSEQUENCE OF DEFICIENT SEROTONERGIC ACTIVITY IN THE CEREBRAL VESSELS:

Migraine is considered a neurovascular disease whose mechanism, according to some data, is initiated in the brain and subsequently affects the blood vessels. According to some researchers, neuronal mechanisms play the key role; according to other scientists — vascular processes do. Some consider them equally important. According to one hypothesis, migraine is caused by increased excitability of the cerebral cortex and impaired control over pain neurons of the trigeminal nucleus in the brainstem. A low level of the neurotransmitter serotonin, also known as 5-hydroxytryptamine, is also considered to exert an influence. It has also been established that calcitonin gene-related peptide (CGRP) is a principal mediator involved in pain transmission in the pathogenesis of migraine.

1. Hamel, E. Serotonin and migraine: biology and clinical implications (English) // Cephalalgia (English)Russian : journal. — 2007. — November (vol. 27, no. 11). — P. 1293—1300. — ISSN 0333-1024. — doi:10.1111/j.1468-2982.2007.01476.x. — PMID 17970989.

ROLE OF SEROTONIN AND SEROTONIN RECEPTORS:

Migraine is unquestionably a multichemical disorder. However, serotonin occupies a special place in the pathophysiology of migraine.

Since the 60s, an enormous number of studies have been devoted to serotonergic mechanisms of migraine. In 1969, Anthony M. et al. demonstrated for the first time a close relationship between migraine attacks and a decrease in platelet serotonin concentration (5HT), which was confirmed in a series of subsequent studies. Alongside this, data have been obtained that permit discussion of possible disturbances in the central serotonergic system in patients with migraine as well. A reduction in platelet serotonin is also observed in migraine complicated by medication-induced headache, while clinical improvement correlates with normalization of its level.

Changes in platelet serotonin levels in migraine are cyclical. A whole series of studies has shown the dynamics of platelet serotonin levels depending on the phase of migraine. Most studies show that the headache attack itself in migraine is associated with a period of reduced 5HT in platelets. On the other hand, the influence of reduced 5HT levels on the development of cortical spreading depression (CSD) has been demonstrated. These data became another focus in the study of migraine pathophysiology and the basis for formulation of the “serotonin hypothesis” of migraine.

At the same time, it was precisely the study of serotonergic mechanisms of migraine that also formed the basis of neuropharmacological research. JW. Lance et al. showed that archetypal vasoconstrictors such as ergotamine, noradrenaline, and serotonin are capable of aborting headaches. From that time, active work began with selective agonists of 5-HT1 receptors, and the degree of affinity for these receptor subtypes became the target in creating an “ideal agonist” for serotonin receptors specific to migraine.

These studies constituted a revolution in the treatment of migraine attacks and provided the basis for creating an entire class of pharmacological agents with agonist properties at particular 5-HT receptor subtypes, on account of which they are classified as specific antimigraine agents because they were synthesized exclusively for treating migraine attacks. This class of selective 5-HT receptor agonists is conventionally called “triptans.” The creation of sumatriptan was promising. Because this drug mimicked the action of serotonin (5-hydroxytryptamine), it received the suffix “triptan” as a reflection of its action on serotonin receptors, whereas “suma” was chosen as a specific prefix for the sulfonamide (5-sulphonamide) group of its chemical structure .

With the introduction of sumatriptan into broad clinical practice in 1990, a new era of specific therapy for migraine attacks effectively began. Sumatriptan, as the first representative of this class of drugs, is the “gold standard” of antimigraine therapy, and most comparative studies of subsequent representatives of the triptans are devoted to comparing the effects under study with the therapeutic action of sumatriptan.

Source: Tabeeva G. R., I. M. Sechenov Moscow Medical Academy. Specific Treatment of Migraine: The History of One Triptan. www.paininfo.ru/articles/1…

Additional literature:

1. Kutsik R. V., Zuzuk B. M. Ergot (ergot sclerotia) — Claviceps purpurea (Fries) Tulasne. Provizor, 2002;12:1-9.

2. Andersen AR., Tfelt-Hansen P., Lassen NA. The effect of ergotamine and dihydroergotamine on cerebral blood flow in man. Stroke, 1987;18:120-3.

3. Anthony M., Hinterberger H., Lance JW. The possible relashion- ship of serotonin to migraine syndrome. Res Clin Headache Stud, 1969;2:29-59.

4. Bouchelet I., Case B., Olivier A. et al. No contractile effect for 5-HT1D and 5-HT1F receptoragonists in human and bovine cerebral arteries: similarity with human coronary artery/ Br J Pharmacol, 2000;129:501-8.

5. Goadsby RB., Hoskin KL. Serotonin inhibits trigeminal nucle- us activity evoked by craniovascular stimulation through a 5-HT1B\1D receptor: a central action in migraine/ Ann Nearol, 1998;43(6):711-8.

6. Chugani DC., Niimura K., Chaturvedi S. et al. Increased brain serotonin synthesis in migraine. Nearology, 1999;53:1473-9.

7. Dobson CF., Tohyama Y., Diksic M. et al. Effects of acute or chronic administration of anti-migraine drugs sumatriptan and zolmitriptan on serotonin synthesis in the rat brain. Cephalalgia, 2004;24:2-11.

8. Doenicke A., Siegel E., Hadoke M., Perrin VL. Initial clinical study of AH25086B (50HT1 — like agonist) in the acute treatment of migraine. Cephalalgia, 1987;7:438-9.

9. Feniuk W., Humphrey PPA., Watts AD. Further characterization of pre- post-junctional receptors for 5-hydroxytrypthamine in isolated vasculature. Br J Pharmacol, 1981;73:191-2.

10. Ferrari MD., Odink J., Tapperelli C., van Kempen GMJ., Pennigs EJM., Bruyn GW. Serotonin metabolism in migraine. Neurology, 1989;39:1239-42.

11. Goadsby PJ., Gundlach AL. Localization of H-dihydroergota- mine binding sites in the cat central nervous system. Ann Nearol, 1991;29:91-4.

12. Goldstein J., Ryan R., Jiang K. et al. Crossover comparison of riza-triptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Headache, 1998;38:737:47.

13. Graham JR., Wolff HG. Mechanisms of migraine headache and action of ergotamine tartrate. Arch Nearol Psuchiatr, 1938;39:737-63.

14. Hering R., Glover V., Pattichis K., Catarchi T., Steiner TJ. 5-HT in migraine with medical-induced headache. Cephalalgia, 1993;13:410-2.

15. Humphrey PPA. The discovery of sumatriptan a new class of drug for the acute treatment of migraine. In: Humphrey PPA., Ferrari MD., Olesen J, eds. The Ttriptans: Novel Drugs in Migraine. Frontiers in Headache Research. Vol 10. Oxford university Press, 2001:3-10.

16. Humphrey PPA., Apperley E., Feniuk W. et al. A rational approach to identifying a fundamentally new dgur for the treatment of migraine. In: Saxena PR., Wallis DI., Wenter SW., Bevan P., eds. Cardiovascular Pharmacology of 5-Hydroxytrypthamine. Dordreht: Kluwer., 1990:417-31.

17. Johnson KW., Schans JM., Durkin MM. et al. 5-HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Neuroreport, 1997;8:2237-40.

18. Lance JW. The mechanism and management of headache. 2nd edn. Butterworth, London, 1973.

19. Lance JW., Anthony M., Somerwille B. Comparative trials of serotonin antagonists in the management of migraine. Br Med J, 1970;2:327-30.

20. Longmore J., Shaw D., Smith D et al. Differential distribution of 5-HT1D and 5-HT1B -immunireactivity within the human trigemino-vascular system: implications for the discovery of a new antimigraine drugs. Cephalalgia, 1997;17:833-42.

21. MaassenVanDenBrink A., Reekers M., Bax A. et al. Coronary side effect potential of current and prospective drugs. Circulation, 1998;98:25030.

22. Muller-Schweinitzer E. In vitro studies on the duration of action of dihydroergotamine. Int J Clin Pharmacol Ther Toxicol, 1980;18:88-91.

23. Nilson T., Longmore J., Shaw D. et al. Contractile 5-HT1B receptors in human cerebral arteries: pharmacological characterization and localization with immunocyto-chemisrty. Br J Pharmacol, 1999;128:1133-40.

24. Pascual J., del Arco C., Romon T. Et al. Autoradiographic distribution of [H] sumatriptan-binding sited in post-mortem human brain. Cephalalgia, 1996;1:317-22.

25. Pfaffenrath V., Cunin G., Sjonell G et al. efficacy and safety of suma-triptan tablets (25 mg, 50 mg, 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan. Headache, 1998;38:184-90.

26. Saxena PR. Selective in carotid vascular by methysergide: possible prevalence to its antimigraine effect. Eur J Pharmacol, 1974;27:99-105.

27. Saxena PR., Ferrari MD. From serotonin receptor classification to the antimigraine drug sumatriptan. Cephalalgia, 1992;12:187-96.

28. Saxena PR. Selective carotid vasoconstriction by ergotamine as a relevant mechanism in its antimigraine action. Arch Neurol (Madr), 1974;37(suppli):301-15.

29. Sarchielli P., Alberti A., Russo S. et al. Nitric oxyde pathways, Ca 2+ and seritonin content in platelets from patients suffering from chronic daily headache. Cephalalgia, 1999;19:810-6.

30. Schiller F. The migraine tradition. Bull History Med, 1975;49:1-19.

31. Srikiatkhachorn A., Anuntasenhakul T., Maneesri S., Phansuwan-Pujito P., Patumraj S., Kasantikul V. Hyposerotonin-induced nitric oxide hypersensibility in the cerebral microcirculation. Headache, 2000;40:267-75.

32. Silberstein SD., McGrory DC. Ergotamine and dihydroergota- mine: history, pharmacology and efficacy. Headache, 2003; 43:144-6.

ROLE OF SEROTONIN RECEPTORS 5-HT1 AND 5-HT7 IN ABORTING OR PREVENTING MIGRAINE:

In addition to insufficient activity of serotonin receptors of the first type, migraine may, on the contrary, be caused by excessive activation of serotonin receptors of the 7th type, whose action is in many respects opposite to that of receptors of the 1st type. Whereas in the case of 5-HT1 receptors their agonists have antidepressant and antimigraine effects, in the case of 5-HT7 receptors (which occur more rarely in the CNS), their antagonists have the same effects.

Strong antagonists of 5-HT₇ receptors include many antidepressants and many atypical antipsychotics, as well as some typical antipsychotics (in particular trifluoperazine, fluphenazine). Alongside other mechanisms, this may partly account for the antidepressant effect of these antidepressants and atypical antipsychotics, as well as the ability of the indicated antipsychotics to potentiate the action of antidepressants.

Antagonists of 5-HT₇ receptors also include many well-known antimigraine drugs, such as methysergide, ketanserin, and ritanserin. It is possible that their antagonism toward 5-HT₇ receptors also contributes to their preventive antimigraine action.

ROLE OF THE INFLAMMATORY MEDIATOR HISTAMINE IN THE PATHOGENESIS OF MIGRAINE:

Another primary cause of migraine may be a substantially elevated level of histaminergic activity in the brain. Presynaptic H3-type histamine receptors suppress the release of neurotransmitters (dopamine, GABA, acetylcholine, serotonin, noradrenaline, histamine itself) from neuronal cell bodies into the synaptic cleft. Histamine thereby inhibits serotonergic activity and reduces the level of available serotonin. This may be one of the reasons for the migraine-provoking effect of elevated7 histamine.

But migraine may also simply be a manifestation of a histamine-related inflammatory process in the form of allergic edema of one half of the brain or impaired circulation in response to food allergens, more rarely–medications. That is, the causes of migraine may have no connection with a low serotonin level (especially since increasing serotonin in migraine does not always help as a treatment).

Patients suffering from migraine attacks show a high prevalence of somatic diseases, among which an important role is assigned to inflammatory reactions and clinical manifestations of immune-system pathology. The principal syndromes in these patients are infectious and allergic – a typical picture for elevated histaminergic activity.

The action of mast cells (from which excess histamine is released in the body) was initially regarded in science as vasodilatory, which was considered the principal cause of migraine development (it is no accident that serotonin, which aborts migraine, constricts vessels), but it was later found that mast cells also play a role in activating the pain pathway underlying headache. They are also capable of crossing the blood-brain barrier, especially in the presence of pathological processes in the body.

Scientists are conducting research aimed at discovering drugs for selective inhibition of histamine release through activation of histamine H3 autoreceptors, which limit this release when excited. H3 receptors are located mainly in the brain and are inhibitory autoreceptors situated on histaminergic nerve endings that regulate histamine release. Examples of selective H3 antihistamine agents include: Ciproxifan, Clobenpropit, Clozapine, Thioperamide. These experimental agents do not yet have a defined clinical application, although a number of drugs are currently undergoing human trials.

For migraine prophylaxis, it has also been proposed to activate highly sensitive inhibitory histamine H3 autoreceptors with low doses of subcutaneous histamine. However, its use is limited by an inconvenient treatment regimen and the possible risk of a rebound reaction.

1. Yagafarova A.V., Zamyshlyaev R.A. THE ROLE OF THE INFLAMMATORY MEDIATOR HISTAMINE IN THE PATHOGENESIS OF MIGRAINE // International Student Scientific Bulletin. – 2018. – № 4-2.; URL: eduherald.ru/ru/article…

PRESENCE OF DEPENDENCIES (ADDICTIONS), EASE OF THEIR FORMATION

(A marker of reduced serotonin)

1. I often abuse something. 0.86

2. Sometimes I am forced to take anti-anxiety medications (tranquilizers) to relieve causeless anxiety that interferes with me. 0.85

3. I still smoke, although I have tried to give up this habit. 0.83

4. Most people have one dependency or another. Count how many dependencies from the list you have in total? (indicate a number from 0 to 9): Lotteries, frequent card games lasting many hours, casinos, computer games for several hours every day, attraction to sports betting, smoking, psychoactive substances, masturbation, mandatory coffee or strong tea multiple times a day, regular drinking, shopping, watching all the news on TV one after another, chatting on Internet forums for several hours every day. 0.81

5. I am often drawn to take something in order to improve my mood. 0.77

6. It is extremely difficult for me to give up some habits, even harmful ones - everything deep inside me immediately begins to rebel against such an unpleasant attempt to deprive me of something. 0.75

7. Some of my habits attract me extremely strongly. I begin to become agitated if I have no opportunity to satisfy them for a long time. 0.73

8. I need psychostimulants - without them it is difficult for me to live effectively and energetically. 0.71

9. I easily become “hooked” on various painkillers. 0.67

10. I admit that I easily develop a dependency on some habitually pleasant but useless activity, or on medications that improve mood (this dependency is then difficult to overcome - I remember it, and I am strongly drawn to it again). 0.60

11. I smoke a pack of cigarettes a day or more. 0.63

12. If something I am accustomed to consuming regularly is not in the house - tea, say, or cigarettes - I begin to get nervous and “twitchy” until I get it. 0.57

13. I have a habit-dependency condemned by some of my close ones, with the help of which I sometimes try to calm my nerves. 0.37

14. It happens that I drink something alcoholic in the morning to calm my nerves. 0.39

15. Sometimes I become tired of criticism from others about my “drinking bouts.” 0.32

16. I believe that I belong to the type of people in whom the formation of any dependencies (on alcohol, drugs, gambling, computers, etc.) occurs more slowly than in others. -0.56

17. When are you more often visited by the thought that it would be good to drink beer? - 1) in the morning 3) in the evening 5) practically never -0.56

18. I do not have any special or harmful food predilections, such as an addiction to sweets. -0.50

ON THE ROLE OF ELEVATED SEROTONIN IN REDUCING ATTRACTION TO ALCOHOL AND PSYCHOACTIVE SUBSTANCES, AS WELL AS IN IMPEDING THE FORMATION OF OTHER DEPENDENCIES:

The results of activation of 5-HT₁A receptors by serotonin or agonists of these receptors include a reduction in behavioral impulsivity, while impulsivity (that is, weakness of rational behavioral control) – is an important factor in the formation of any dependencies:

1. Winstanley C. A., Theobald D. E., Dalley J. W., Robbins T. W. Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders (English) // Neuropsychopharmacology (English)Russian : journal. — Nature Publishing Group, 2005. — Vol. 30, no. 4. — P. 669—682. — doi:10.1038/sj.npp.1300610. — PMID 15688093.

Another (although secondary) reason for the association of low serotonin with predisposition to dependencies (addictions) is that low serotonin is associated with feelings of psychological discomfort, dissatisfaction, and often depressive states. Seeking to escape this state, people with low serotonin often look for drugs that could alleviate their condition and make it psychologically more comfortable. But this reason is nevertheless not the principal one. The principal reason for the negative relationship between serotonin and addictions (and the positive relationship between addictions and serotonin deficiency) is that serotonin partially suppresses dopamine transmission, which is absolutely necessary for the formation of any dependencies.

This is evidenced, in particular, by the fact that the results of activating 5-HT₁A receptors with serotonin or simply with their agonists (and it is precisely these receptors that inhibit dopamine transmission) in fact also include a reduction in attraction to alcohol and psychoactive substances:

1. Tomkins D. M., Higgins G. A., Sellers E. M. Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake (English) // Psychopharmacology (English)Russian : journal. — Springer, 1994. — Vol. 115, no. 1—2. — P. 173—179. — doi:10.1007/BF02244769. — PMID 7862892.

2. Müller C. P., Carey R. J., Huston J. P., De Souza Silva M. A. Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors (English) // Prog. Neurobiol. : journal. — 2007. — Vol. 81, no. 3. — P. 133—178. — doi:10.1016/j.pneurobio.2007.01.001. — PMID 17316955.

3. Carey R. J., DePalma G., Damianopoulos E., Shanahan A., Müller C. P., Huston J. P. Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects (English) // Brain Res. (English)Russian : journal. — 2005. — Vol. 1034, no. 1—2. — P. 162—171. — doi:10.1016/j.brainres.2004.12.012. — PMID 15713268.

Serotonin suppresses the “feeling of craving” in alcoholism. This action also develops with the use of serotonin reuptake inhibitors (SSRIs), partial 5-HT1A agonists, 5-HT2 antagonists, and 5-HT3 antagonists. All these agents exert an inhibitory effect on dopaminergic projections from the ventral tegmentum (ventral tegmental area) to the ventral striatum (nucleus accumbens, NAc). Since any drug craving relies on these dopaminergic projections, serotonin therefore weakens it to some extent:

1. Bokhan N. A. Ivanova S. A., Levchuk L. A. The Serotonin System in the Modulation of Depressive and Aggressive Behavior. - Tomsk: Ivan Fedorov Publishing House, 2013. 102 p. www.mental-health.ru/files/edu/…

Evidence of serotonergic involvement in the genesis of nonchemical dependencies includes, in particular, studies of addiction-induced disturbances in platelet monoamine oxidase B (MAO-B), whose activity correlates with the level of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in cerebrospinal fluid. MAO-B is considered a peripheral marker of serotonin functions. A low level of 5-HIAA correlates with a high level of impulsivity and sensation seeking, which was found in individuals with pathological gambling and those abusing psychoactive substances [Blanco C et al.,1996]. Pharmacological studies of the hormonal response after administration of serotonergic drugs also indicate serotonergic dysfunction (reduced serotonergic activity) both in behavioral dependencies and in chemical addicts [Griffiths M.D., 1998]:

1. Egorov A.Yu. Nonchemical (Behavioral) Addictions: Issues of Typology, Diagnosis, and Classification. ISSUES OF NARCOLOGY • № 4 (187) • 2020

2. Blanco C., Orensanz-Muñoz L., Blanco-Jerez C., Saiz-Ruiz J. Pathological gambling and platelet MAO activity: a psychobiological study // Am J Psychiatry. – 1996. – Vol. 153. – N1. – P. 119–121.

3. Griffiths M.D. Internet addiction: does it really exist? // Psychology and the Internet: Intrapersonal,interpersonal, and transpersonal implications / J. Gackenbach (Ed). – San Diego, CA, Academic Press, 1998. – P. 61–75

The reason for the inhibitory action of serotonin and agonists of its 5-HT1A receptors on the formation of dependencies is evidently connected with the inhibitory effect of 5-HT1A receptor activation on dopamine transmission. Dopamine transmission is the basis for reinforcement of any dependency, and not only drug dependency. Thus, a number of studies have shown increased dopamine release in the striatum of problem gamblers, as well as positive correlations between dopamine release and the severity of gambling dependency. In other behavioral dependencies, the dopaminergic system may likewise play a key role in the formation of symptoms. For example, dopamine agonists can lead to hypersexual behavior in patients with Parkinson’s disease (who are treated with these agonists).

What is the mechanism of the inhibitory (antagonistic) action of serotonin on dopamine? Serotonin 5-HT1A receptors may be both postsynaptic and presynaptic. In their presynaptic variant, they inhibit the release of neurotransmitter from the neuron into the synapse, that is, they impede neuronal conduction. In their postsynaptic variant, they excite the next neuron in the chain and stimulate neuronal transmission. When serotonergic neurons are involved, the two effects act in different directions and balance one another, to a substantial extent stabilizing serotonergic conduction. But serotonin-sensitive presynaptic 5-HT1A autoreceptors are found, as it turns out, on the cell bodies not only of serotonergic neurons, but also of dopaminergic neurons (which transmit excitation in the synapse through dopamine), glutamine neurons, noradrenergic neurons, and acetylcholine neurons. Presynaptic 5-HT1A autoreceptors are present on the bodies of these neurons, whereas postsynaptic receptors of this type, capable of enhancing neurotransmission, are absent from the bodies of these neurons. Therefore, by activating these receptors, free extracellular serotonin, in the case of “nonserotonergic” neurons, can only inhibit neurotransmission along any “nonserotonergic” neurons on whose bodies its 5-HT1A receptors are present. Free serotonin also inhibits dopaminergic transmission, limiting the release of dopamine into synapses from the axons of dopaminergic neurons.

It is precisely for this reason that serotonin is said to have an inhibitory role in the nervous system. It reduces the release of dopamine, noradrenaline, glutamate, and partly acetylcholine in any neurons that are “not its own,” thereby limiting “foreign” neurotransmission based on other neurotransmitters.

By partially limiting the release, in particular, of dopamine, serotonin thereby also limits the formation of drug and psychological dependencies.

If only this mechanism operated in the case of serotonin, serotonin would be in rigid opposition to all other neurotransmitters. Yet this opposition is still moderate, because through some of its other receptors serotonin is capable, on the contrary, of stimulating the release of dopamine and noradrenaline. In addition, there are agents capable of “bypassing” the inhibitory action of serotonin autoreceptors on the release of any neurotransmitters into the synapse. For example, the well-known MDMA (ecstasy) produces such an effect, stimulating the release into synapses of serotonin, noradrenaline, dopamine, and acetylcholine simultaneously.

In addition to the role of serotonin 5-HT1A autoreceptors in limiting dopaminergic neurotransmission, activation of serotonin receptors of the 5-HT 2C type also plays a role in this; their activation likewise leads to a reduction in dopamine release into the mesocorticolimbic pathway, whereas deactivation by antagonists – on the contrary, leads to an increase in dopaminergic and noradrenergic activity in the frontal cortex. Since all mechanisms of dependency formation are tied to dopamine release, which encourages reinforcement of habits, activation by serotonin of its 5-HT1A and 5-HT 2C receptors therefore impedes the formation of dependencies (all dependencies, and not only those on alcohol and drugs).

Numerous human gene polymorphisms affecting expression of 5-HT 2C have been identified. Polymorphism of this protein correlates with susceptibility to a range of conditions, including psychiatric disorders, depression, OCD, obesity, and substance-use disorders.

Activation of 5-HT 2C by serotonin, leading to an enhanced reduction in dopamine transmission, is responsible for many negative side effects of SSRI and SNRI drugs – namely, in some patients this agonistic effect of serotonin on 5-HT 2C can lead to worsening symptoms of anxiety and depression (through inhibition of dopaminergic mechanisms). Modern “atypical antipsychotics,” while also increasing serotonin overall, circumvent this point by additionally blocking 5-HT 2C receptors through their own action and thereby simultaneously enhancing dopamine transmission.

1. Alex KD, Yavanian GJ, McFarlane HG, Pluto CP, Pehek EA (March 2005). “Modulation of dopamine release by striatal 5-HT2C receptors”. Synapse. 55 (4): 242–51. doi:10.1002/syn.20109. PMID 15668911.

Several further details must be added to everything said about the predominantly inhibitory action of serotonin on the formation of dependencies (addictions).

a) Specifically with regard to alcohol, although serotonin inhibits the formation of dependency (by slowing dopamine release), with respect to alcohol consumption itself it is rather a predisposing factor. The point is that after ingestion alcohol leads to serotonin depletion and reduces serotonergic transmission overall. Therefore, individuals with initially high levels of serotonergic activity can consume higher doses of strong alcohol without experiencing psychological discomfort.

b) At present, much is already known about the functions of the insular cortex of the brain. One of these important functions is maintenance of bodily homeostasis. Activity of the insular cortex is associated with the emergence of motivations aimed at restoring homeostasis. If a person does not receive something habitual, the insular cortex forms a feeling of frustration (dissatisfaction of a need) and motivation directed toward restoring the “status quo.” It is clear that this mechanism is also important in maintaining any established dependencies – whether smoking, drugs, gaming, or the habit of one’s favorite house slippers.

Such a function of the insular cortex requires, in all probability, enhanced dopaminergic transmission in this area and a reduction in the number of serotonin 5-HT1A receptors that impede dopaminergic mechanisms. We found no indications in the literature that these hypotheses have been studied and tested, but they seem fairly probable.

It should also be mentioned that markers of an active insular cortex in socionics are most closely associated with the pole of Questimity. One should therefore expect that the property of increased susceptibility to dependencies will also be partly linked to the pole of Questimity, whereas the opposite property of tolerance to addictions will, on the contrary, be linked to the pole of Declatimity (as, possibly, will the averaged profile of serotonergic activity as a whole – especially since the effects of serotonin, according to a number of other markers besides tolerance to addictions, are also characterized by suppression of frustration reactions)

We continue the flash mob of serotonin markers. It turns out that having high serotonin is not always and not in every respect good, and memory functions (and, in a broader sense, cognitive abilities as well) are an example of this.

Thus, MEMORY

Good memory, as we will show below, – is a marker of REDUCED serotonin.

DIFFERENT MEMORY CLUSTERS:

1. Verbal memory (poems, jokes, names)

2. Memory for numbers (dates, telephone numbers, distances)

3. High interest in world political history

4. Good rote memory for historical dates

5. Correlates of accurate memory for historical dates (general memory, speed and flexibility of thinking, interest in numbers, meticulousness regarding minute factual accuracy)

6. Selectively strong and “sticky” memory for any negative material.

7. Strong memory for positive recollections.

8. Ease of recalling and selecting the required word, name, analogy

9. Good visual memory

10. Good operational, working memory - with large capacity, long-lasting and without dropouts, resistant to interference from sudden signals

11. Well-functioning semantic long-term memory, memory for facts, with highly selective identification of what is most important.

12. Well-developed episodic-memory system - with access to a broad range of recollections, their linkage to the time and context of events, as well as constant comparison of memories and images from different situations and times

13. Rich memory for interrelationships, especially those based on temporal linkage of past facts and events.

14. Well-controlled, rapid, and flexible associative memory, free from sudden “braking” and getting stuck

15. Good retention in memory and constant scanning in consciousness of all current plans and obligations

16. Good memory for poetry, likes it and remembers many poems

17. Good memory for people’s names

18. Good memory for individual people’s voices

19. Very good memory for smells.

We averaged the socionic profiles of all these clusters and obtained, for the averaged characteristics of GOOD, PROBLEM-FREE MEMORY, the result shown in Tables 1 and 2.

We also selected questionnaire items most closely correlated with the resulting averaged profile of good, problem-free memory.

Below we also present a scale-list of these items, reflecting the personality portrait of a person with good development of most types of memory:

CORRELATES OF THE AVERAGED PROFILE OF 19 CLUSTERS OF GOOD MEMORY (in content - excellent development of frontal speech areas, rapid memory, problem-free attention, concentration, tracking a large number of details, activity and initiative, self-confidence, categoricalness). In essence, in this personality portrait we obtain a reflection of high activity of dopamine, acetylcholine, and noradrenaline in the prefrontal cortex:

1. My sentences are always perfectly smooth, without any hesitations in their oral construction and without any need for subsequent correction of word order in writing. 0.89

2. I quickly find in memory, in the right place, the necessary association or recollection, without slipping onto irrelevant material. 0.80

3. I have excellent attention, which rarely misses anything. 0.79

4. I am always very categorical in my statements and actions. 0.79

5. I fairly often make remarks to people. 0.78

6. I am so confident in the exclusive correctness of my way of thinking and my life values that, whenever possible, I always try to impose them on others. 0.77

7. I condemn other people’s behavior more often than I am prepared to understand and accept it. 0.76

8. I am inclined to impose my own rules. 0.76

9. Compared with other people, I devote more attention and time to a healthy lifestyle and to maintaining good health. 0.75

10. I characteristically and habitually keep very careful account of all small details in the sequence of carrying out some undertaking. 0.74

11. I am very intolerant of disorder and untidiness. 0.74

12. I have a very good sense of correctly constructed, smoothly flowing speech, a “feel for language.” 0.74

13. I retain in memory most facts I hear. 0.74

14. I usually conduct conversations at length, in detail, and thoroughly. 0.74

15. In the course of mental analysis I recall and note every small detail. 0.74

16. I like telling everyone which path they should take and which opportunity they should use. 0.74

17. I like instructing new employees or simply newcomers to some activity. 0.74

18. At least when I speak fluently, my speech contains many random, parasitic, meaningless, or incorrectly chosen words. -0.87

19. I have difficulty formulating an utterance, translating my already-formed thoughts into extended speech. -0.81

20. When I express myself aloud, my sentences come out somewhat awkward; it is not easy for me to translate an intention into an external, extended utterance. -0.81

21. If nothing from outside arouses me or asks me any questions, I am often overcome by a drowsy, inhibited state. -0.80

22. I easily and often forget, until the next occasion, ideas that had come to mind for a time. -0.80

23. I have problems with memory. -0.80

24. Sit on a chair, place your bare legs in front of you on your heels and bend the toes of both feet as far as you can (away from yourself). See which foot’s big toe you managed to bend farther (of course, without using your hands). Record the number of the appropriate response option: 1) If you managed to bend the big toe of the left foot farther, while the toe of the right foot does not bend as successfully. 3) If the big toes of both feet bent exactly equally. 5) If you managed to bend the big toe of the right foot farther, that is, through a greater angle, while the toe of the left foot does not bend as successfully. -0.79

25. When I speak aloud, I often make “uh-uh-uh..” and “mm-uh-uh…” sounds while trying to find the right word somewhere “in the air.” -0.79

26. It is difficult for me to repeat someone’s complicated surname aloud - I often stumble when pronouncing combinations of sounds. -0.78

27. When I sit and think about something, afterward I find it difficult to say how much time has passed: fifteen minutes or thirty. -0.78

28. I sometimes make mistakes and become confused when pronouncing phonetically “difficult” words containing many consonants. -0.78

29. In my affairs there is always a romantically unfinished element; sometimes even I myself do not fully know what I am going to do, and all the more I will not discuss it. -0.76

30. I have difficulty learning and remembering verbal material - poems, surnames, names, telephone numbers, etc. -0.76

31. I have a poor sense of direction. -0.76

32. I sometimes notice that it is difficult to carry out a chain of different alternating movements - either pauses arise when switching from one movement to another, or the old movement begins automatically to repeat several times. -0.75

33. When new facts arrive, I quickly change my point of view. -0.75

34. There are moments when I automatically perform some complex actions and afterward cannot account to myself for exactly what I was doing (that is, everything is quickly forgotten). -0.75

35. In my sleep, without waking up, I sometimes begin to say something aloud. -0.75

36. I have problems with the capacity of attention - I often fail to notice something important. -0.74

37. I have a certain natural inarticulateness - it is difficult to construct phrases quickly and smoothly (both orally and in writing). -0.74

38. When I type text on a keyboard, my finger movements are usually jerky and awkward; there is no single smooth “melody of tapping.” -0.74

39. I sometimes make mistakes in carrying out instructions because I incorrectly understand by ear exactly what I was instructed to do and what was wanted from me. -0.73

40. I have almost never managed to assimilate lecture material directly during lectures - at some point I would inevitably “drop out” of the explanation, and afterward I always had to assimilate the material again by reading the textbook and notes with my own eyes. -0.73

41. When I am agitated, it is as though my “tongue sticks” - I lose the ability to express my thoughts effectively aloud. -0.73

In the trait profiles of good memory, the attached tables show strengthening of the poles of process, foresight, and merriness – that is, the very poles that in other serotonin markers are also usually associated with LOW SEROTONIN.

As for the strongly elevated extraversion - this is an obvious consequence of the long-known important role in “good memory” of the quartet of excitatory neurotransmitters, each of which makes its own contribution to extraversion as well: acetylcholine, glutamate, noradrenaline, dopamine.

But still, what does serotonin have to do with this? Why, as we wrote at the very beginning of the post, is specifically low CNS serotonin correlated with good memory, while high serotonin is correlated with poor and weak memory?

About this, with a theoretical analysis, in detail and with a literature review – in the next post, in a few minutes

ON THE NEGATIVE INFLUENCE OF SEROTONIN ON MEMORY, ATTENTION, AND INTELLECTUAL ACTIVITY (continuation; see the beginning in the previous post)

Thus, what does serotonin have to do with this; why, as we wrote in the first part of the post, is low CNS serotonin correlated with good memory, while high serotonin is correlated with poor and weak memory?

In the shortest possible terms – because serotonin suppresses the neurotransmission (primarily in the hippocampus, but partly also in the prefrontal cortex) on which any good memory is built. Namely, acetylcholine (“cholinergic”), dopamine, noradrenaline, and glutamate neurotransmission.

Thus, it has been shown that activation of the most “numerous” serotonin 5-HT₁A receptors in the CNS (by serotonin or their other agonists) can impair memory functions (this concerns both declarative and non-declarative memory) and learning ability (as a consequence of disruption of the mechanisms for encoding and storing new information in memory). This occurs through inhibition of glutamate and acetylcholine release in various brain regions – primarily in the hippocampus. It is possible that this effect underlies the adverse influence of antidepressants on memory that is sometimes observed:

1. Ogren S. O., Eriksson T. M., Elvander-Tottie E., D’Addario C., Ekström J. C., Svenningsson P., Meister B., Kehr J., Stiedl O. The role of 5-HT(1A) receptors in learning and memory (English) // Behav. Brain Res. (English)Russian : journal. — 2008. — Vol. 195, no. 1. — P. 54—77. — doi:10.1016/j.bbr.2008.02.023. — PMID 18394726.

Conversely, it has been shown that antagonists of 5-HT₁A receptors, such as lecozotan, are capable of improving certain aspects of learning and memory, at least in experiments on rats, and as a consequence they are currently being studied as potential candidate drugs for the treatment of Alzheimer’s disease:

2. Spreitzer H. Neue Wirkstoffe - Lecozotan (German) // Österreichische Apothekerzeitung. — 2008. — 13 August (№ 17/2007). — P. 805.

At the same time, it is known that activation of 5-HT₁A receptors is capable of partly improving certain sensory cognitive functions associated with increasing the quality of information filtering – simply put, by cutting off access of excessive associations to consciousness, to the prefrontal cortex. In this case serotonin makes its partly positive contribution to cognitive processes merely by working “for sensing” and “against intuition.” Moreover, the greatest benefit from this is obtained by pronounced schizothymics and patients with schizophrenia, whose initial sensory status is sharply weakened:

3. Meltzer H. Y., Sumiyoshi T. Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia? (English) // Behav. Brain Res. (English)Russian : journal. — 2008. — December (vol. 195, no. 1). — P. 98—102. — doi:10.1016/j.bbr.2008.05.016. — PMID 18707769.

The principal reason for the negative influence of serotonin on memory is that serotonin, through its 5-HT1A receptors, mainly (in most brain structures) INHIBITS (suppresses) the activity of other important neurotransmitters involved both in cognitive functions and in elevating mood – noradrenaline, dopamine, acetylcholine, and glutamate. This is both a reason for weakening cognitive functions under the action of serotonin and a reason for the low efficacy of “pure” 5-HT1A receptor agonists as potential antidepressant agents.

The reason for the inhibitory action of serotonin and agonists of its 5-HT1A receptors on dopaminergic, noradrenergic, and glutamatergic transmission consists (as we have already written in previous posts) in the following: presynaptic serotonin 5-HT1A receptors “sit” on the bodies of other (nonserotonergic) neurons and, when excited by serotonin, inhibit the release of ANY neurotransmitter from these neurons, - thus serotonin inhibits acetylcholine, glutamate, noradrenaline, and dopamine neurotransmission in the hippocampus, basal ganglia, and prefrontal cortex alike.

Slowing dopamine is partly useful for cognitive processes in cases where dopamine is initially excessively high anyway (for example, in ethical-intuitive types). In this case, serotonin’s slowing of dopamine limits the “free” and weakly controlled associative process and thereby “lowers” excessively overgrown intuition, raising sensing instead. The entire cognitive gain from serotonin consists, and can consist, only in this; even then, it is useful only for schizothymics.

But inhibition of the other three types of neurotransmission – acetylcholine, glutamate, and noradrenaline – is already unequivocally bad for cognitive processes, and especially for any types of memory. This is because memory, attention, and intelligence (the speed of thought processes) rest precisely on the active functioning of these three neurotransmitters: acetylcholine, glutamate, and noradrenaline.

It can be said that excessive serotonin leads to a certain dull-wittedness. And by virtue of other properties of serotonin that suppress anxiety, search, and doubt, - to a narrowly self-satisfied dull-wittedness as well. And, unfortunately, such words about the personality profile of particularly high serotonin would be true.

Thus, because acetylcholine, noradrenaline, and glutamine neurotransmission are most important for memory and cognitive processes, serotonin, by exerting in most brain regions a predominantly inhibitory (suppressive) effect on these types of transmission through its 5-HT1A receptors on the bodies of specific acetylcholine, dopamine, noradrenaline, and glutamate neurons, has on the whole a predominantly negative effect on cognitive functions (and especially memory), impairing them:

1. Rothman R. B., Baumann M. H.Therapeutic potential of monoamine transporter substrates (English) // Curr Top Med Chem journal. — 2006. — Vol. 6, no. 17. — P. 1845—1859. — doi:10.2174/156802606778249766. — PMID 17017961.

2. Scorza C., Silveira R., Nichols D. E., Reyes-Parada M. Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action (English) // Neuropharmacology : journal. — 1999. — July (vol. 38, no. 7). — P. 1055—1061. — doi:10.1016/S0028-3908(99)00023-4. — PMID 10428424.

3. Marona-Lewicka D., Nichols D. E. Drug discrimination studies of the interoceptive cues produced by selective serotonin uptake inhibitors and selective serotonin releasing agents (English) // Psychopharmacology (English)Russian : journal. — Springer, 1998. — July (vol. 138, no. 1). — P. 67—75. — doi:10.1007/s002130050646. — PMID 9694528.

A sharp reversible deterioration of memory under the action of increased serotonin release into the synaptic cleft is clearly visible in the well-known example of the action of MDMA (“ecstasy”), which very strongly impairs memory in “club dancers” for the duration of its action while simultaneously increasing production of serotonin, dopamine, noradrenaline, acetylcholine, as well as the hormones cortisol and oxytocin. Neither dopamine nor noradrenaline, and especially not acetylcholine, can in principle exert a negative influence on memory. Of the hormones named, only elevated cortisol is capable of negatively affecting memory. However, although cortisol partly affects nerve-signal transmission and memory, the relationship between its release and the subjective effects of MDMA administration is unclear and generally doubtful, because preliminary administration of the cortisol-synthesis inhibitor metyrapone completely blocks the increase in blood hormone concentration after MDMA administration but does not in any way alter the memory deterioration and mood change occurring under the influence of MDMA.

Consequently, the entire negative effect of MDMA on memory remains to be associated only with the effects of elevated serotonin, which is released into the synaptic cleft in especially large quantities under the action of MDMA (this occurs because MDMA “reverses” the serotonin reuptake mechanism – instead of taking serotonin from the synapse and pumping it back into the neuron, under the action of MDMA this mechanism begins intensively pumping serotonin out of the neuron into the synaptic cleft):

1. MAPS. INVESTIGATOR’S BROCHURE: 3,4-methylenedioxymethamphetamine (MDMA) . — 7. — August 1, 2013.

2. Kuypers K. P., de la Torre R., Farre M., Pujadas M., Ramaekers J. G. Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory // British journal of pharmacology. — 2013. — Vol. 168, no. 3. — P. 607—17. — ISSN 1476-5381. — doi:10.1111/j.1476-5381.2012.02196.x. — PMID 22946487.

It should be noted that not all serotonin receptors affect cognitive processes as negatively as its 5-HT1A receptor. If this receptor were serotonin’s only “lawful representative,” then as serotonin concentrations increased a person would generally come to resemble a patient with senile Alzheimer’s dementia. However, the 5-HT2A receptor (which nevertheless occurs less frequently in the CNS than the receptor of the first type), by contrast, stimulates glutamate transmission in the prefrontal, parietal, and somatosensory cortex, as well as in the olfactory bulb, thereby ultimately improving attention and working memory:

1. Bortolozzi A., Díaz-Mataix L., Scorza M. C., Celada P., Artigas F. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity // J. Neurochem.: journal. — 2005. — Vol. 95, no. 6. — P. 1597—1607. — doi:10.1111/j.1471-4159.2005.03485.x. — PMID 16277612.

2. Harvey J. A. Role of the serotonin 5-HT(2A) receptor in learning // Learn. Mem. : journal. — 2003. — Vol. 10, no. 5. — P. 355—362. — doi:10.1101/lm.60803. — PMID 14557608.

3. Williams G. V., Rao S. G., Goldman-Rakic P. S. The physiological role of 5-HT2A receptors in working memory // J. Neurosci. (English)Russian : journal. — 2002. — Vol. 22, no. 7. — P. 2843—2854. — PMID 11923449.

Agonists of 5-HT2A receptors also increase the level of dopamine in the prefrontal cortex, which, on the one hand, can lead to hallucinations and psychosis, but on the other hand improves memory and attention, which plays a role in learning processes:

1. Wingen M., Kuypers K.P., Ramaekers J.G. The role of 5-HT1a and 5-HT2a receptors in attention and motor control: a mechanistic study in healthy volunteers // Psychopharmacology : journal. — Springer, 2007. — Vol. 190, no. 3. — P. 391—400. — doi:10.1007/s00213-006-0614-x. — PMID 17124621.

2. Wingen M., Kuypers K.P., Ramaekers J.G. Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI // J. Psychopharmacol. (Oxford) : journal. — 2007. — Vol. 21, no. 5. — P. 477—485. — doi:10.1177/0269881106072506. — PMID 17092965.

Binding of labeled radioactive 18F-altanserin decreases in healthy individuals during aging, indicating the loss of specific 5-HT2A receptors with age. This may be one of the causes of deterioration in memory, cognitive abilities, motivation, and energy level with age.

Stimulation of another type of serotonin receptor - 5-HT4 receptors – also has a positive effect on cognitive function, in particular on memory and learning processes. Activation of this receptor type is considered to facilitate dopamine neurotransmission:

1. Improving the treatment of schizophrenia: role of 5-HT receptors in modulating cognitive and extrapyramidal motor functions. www.ncbi.nlm.nih.gov/pubmed/238…

There is another distinct type of serotonin receptor that affects cognitive processes, and does so differently from all the previously considered receptors. These are 5-HT6 receptors, and the effect of their activation in many respects resembles the inhibitory influence on memory and cognition exerted by inhibitory serotonin 5-HT1A receptors. However, the mechanism of the negative effect on memory of 5-HT₆ receptors is entirely different. Unlike 5-HT1A receptors, they do not inhibit but excite the neuron on which they “sit.” The point, however, is that most of them are located on “inhibitory” GABAergic neurons, and therefore stimulation of 5-HT₆ receptors produces, overall, an effect of general suppression of CNS activity:

1. Schechter L.E., Lin Q., Smith D.L., et al. Neuropharmacological profile of novel and selective 5-HT₆ receptor agonists: WAY-181187 and WAY-208466 (English) // Neuropsychopharmacology (English)Russian : journal. — Nature Publishing Group, 2008. — May (vol. 33, no. 6). — P. 1323—1335. — doi:10.1038/sj.npp.1301503. — PMID 17625499.

Be that as it may, blockade of central 5-HT₆ receptors increases glutamatergic, noradrenergic, dopaminergic, and cholinergic neurotransmission in various brain regions:

1. Dawson L.A., Nguyen H.Q., Li P. In vivo effects of the 5-HT₆ antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate (English) // British Journal of Pharmacology : journal. — 2000. — May (vol. 130, no. 1). — P. 23—6. — PMID 10780993.

2. Dawson L.A., Nguyen H.Q., Li P. The 5-HT₆ receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus // Neuropsychopharmacology : journal. — Nature Publishing Group, 2001. — November (vol. 25, no. 5). — P. 662—668. — PMID 11682249.

3. King M.V., Sleight A.J., Woolley M.L., Topham I.A., Marsden C.A., Fone K.C. 5-HT₆ receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation—an effect sensitive to NMDA receptor antagonism // Neuropharmacology : journal. — 2004. — August (vol. 47, no. 2). — P. 195—204. — doi:10.1016/j.neuropharm.2004.03.012. — PMID 15223298.

4. Upton N., Chuang T.T., Hunter A.J., Virley D.J. 5-HT₆ receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease // Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics : journal. — 2008. — July (vol. 5, no. 3). — P. 458—469. — PMID 18625457.

Whereas activation of 5-HT₆ receptors enhances GABAergic neurotransmission throughout the CNS:

1. Schechter L.E., Lin Q., Smith D.L., et al. Neuropharmacological profile of novel and selective 5-HT₆ receptor agonists: WAY-181187 and WAY-208466 (English) // Neuropsychopharmacology (English)Russian : journal. — Nature Publishing Group, 2008. — May (vol. 33, no. 6). — P. 1323—1335. — doi:10.1038/sj.npp.1301503. — PMID 17625499.

Antagonists of 5-HT₆ receptors enhance the release of dopamine and noradrenaline in the frontal cortex, whereas stimulation of 5-HT₆ receptors produces the opposite effect (suppression of dopamine and noradrenaline release):

1. Upton N., Chuang T.T., Hunter A.J., Virley D.J. 5-HT₆ receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease // Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics : journal. — 2008. — July (vol. 5, no. 3). — P. 458—469. — doi:10.1016/j.nurt.2008.05.008. — PMID 18625457.

2. Schechter L.E., Lin Q., Smith D.L., et al. Neuropharmacological profile of novel and selective 5-HT₆ receptor agonists: WAY-181187 and WAY-208466 (English) // Neuropsychopharmacology (English)Russian : journal. — Nature Publishing Group, 2008. — May (vol. 33, no. 6). — P. 1323—1335. — doi:10.1038/sj.npp.1301503. — PMID 17625499.

3. King M.V., Marsden C.A., Fone K.C. A role for the 5-HT1A, 5-HT₄ and 5-HT₆ receptors in learning and memory // Trends: journal. — 2008. — September (vol. 29, no. 9). — P. 482—492. — doi:10.1016/j.tips.2008.07.001. — PMID 19086256.

Thus, most of serotonin’s effects on neuronal transmission (acetylcholine, glutamine, noradrenaline, dopamine) that supports the processes of memory and attention are negative and suppressive. Therefore, profiles of weakened memory, attention, and intellectual interests can be regarded as partial markers of the influence of elevated serotonin. And profiles of good memory – as a marker of LOW serotonin.

INTEREST IN PHILOSOPHY, ABILITY FOR PHILOSOPHICAL REASONING AND THEORETICAL DISCUSSIONS.

1. I am very interested in philosophical concepts of the structure of the world. 0.96

2. I like to absorb or construct such theories of my own that will almost certainly never be recognized by society. 0.92

3. I am able to enjoy philosophical reflection. 0.91

4. I like philosophy and science 0.88

5. I like thinking about abstract ideas. 0.88

6. I have some “overvalued” ideas (which look that way in the eyes of some acquaintances). 0.84

7. In my personal library at home: 1) fewer than 10 books 2) from 10 to 50 books 3) from 50 to 200 books 4) from 200 to 500 books 5) more than 500 books 0.83

8. I often spend several days participating on the Internet in some prolonged “scholastic” disputes on abstract topics. 0.83

9. I am usually more interested in theory than practice in everything. 0.82

10. I like to “dig into” and work out complex problems. 0.78

11. In my thoughts I often prove something to someone. 0.78

12. I like dealing with cause-and-effect relationships among numerous facts. 0.76

13. I have always been interested in the general philosophical laws of dialectics, the laws governing the motion of matter. 0.74

14. I am inclined to become excessively fixated on certain ideas. 0.73

15. I often think about abstract philosophical topics. 0.62

16. The work of a philosopher would suit me better than the work of an investigator. 0.56

17. I know well what such philosophical concepts as the uncertainty relation, the principle of complementarity, and the law of the unity and struggle of opposites mean. 0.50

18. I like esoteric and philosophical literature about the structure of the world. 0.37

19. Abstract ideas and reasoning are difficult for me. -0.88

20. I think about the fate of the world and humanity: 1) Often, more often than others 3) Like everyone else 5) Rarely -0.86

21. It is true that I do not like and avoid conversations on “lofty” topics. -0.86

22. There is little point in racking one’s brain over why something happens and how something works -0.84

23. I am not interested in theoretical discussions. -0.83

24. Knowledge must bring quick benefit; otherwise what the hell is it for. -0.82

25. I avoid philosophical reasoning. -0.81

26. I do not like philosophizing. -0.81

27. It is very important for me to find at least some explanation for every fact; I leave it to others to bring all these explanations together into a single theory. -0.75

28. I would be more interested in songs accompanied by guitar than in philosophy. -0.75

29. I usually become bored if people around me talk about politics or science. -0.72

30. It is true that questions concerning the philosophy of being, the boundaries of the human “self,” and the like have never seriously occupied me. -0.67

31. In general I do not like philosophizing. -0.63

32. I usually feel indifferent to all kinds of philosophical questions. -0.60

Why can interest in global, philosophical-worldview questions be classified among markers of reduced serotonin?

As we showed here: vk.com/wall-168821911_45536 , serotonin NEGATIVELY affects memory, cognitive functions, and intellectual activity. This is due to its inhibitory influence on the system of all excitatory neurotransmitters – acetylcholine, dopamine, noradrenaline, glutamate. It is clear that with higher-quality cognitive functions (that is, with reduced serotonin activity), interest in philosophical and other “global” questions extending beyond the individual’s current everyday needs will be appreciably higher.

In addition, serotonin increases suggestibility and conformity because it activates release of the hormone oxytocin into the blood. Oxytocin in turn increases suggestibility and conformity. These two qualities, which are enhanced by oxytocin in women during the period of feeding and rearing a child, are good for increasing empathy and intragroup solidarity but are completely unsuitable for engaging in philosophy and political science. We have not yet provided references on the association of serotonin with an increase in oxytocin under its influence; here they are:

Oxytocin neurons of the pituitary are activated through stimulation of serotonin 5-HT1A receptors in the pituitary. The joint release and synergism of serotonin and oxytocin under the action of ecstasy is to a large extent based on this:

1. M. R. Thompson, P. D. Callaghan, G. E. Hunt, J. L. Cornish, I. S. McGregor. A role for oxytocin and 5-HT1A receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine («ecstasy») (English) // Neuroscience (English)— Elsevier, 2007. — Vol. 146, no. 2. — P. 509—514. — doi:10.1016/j.neuroscience.2007.02.032.

2. Michael White C. How MDMA’s pharmacology and pharmacokinetics drive desired effects and harms (English) // Journal of clinical pharmacology. — 2014. — Vol. 54, no. 3. — P. 245—52. — ISSN 1552-4604. — doi:10.1002/jcph.266. — PMID 24431106.

3. Liechti Matthias E. Effects of MDMA on body temperature in humans (English) // Temperature. — 2014. — Vol. 1, no. 3. — P. 192—200. — doi:10.4161/23328940.2014.955433

Activation of 5-HT2A receptors in the hypothalamus also causes an increase in the levels of such hormones as oxytocin, prolactin, ACTH, cortisol, and renin:

1. Van de Kar L. D., Javed A., Zhang Y., Serres F., Raap D. K., Gray T. S. 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells // The Journal of neuroscience : the official journal of the Society for Neuroscience : journal. — 2001. — Vol. 21, no. 10. — P. 3572—3579. — PMID 11331386.

2. Zhang Y., Damjanoska K. J., Carrasco G. A., Dudas B., D’Souza D. N., Tetzlaff J., Garcia F., Hanley N. R., Scripathirathan K., Petersen B. R., Gray T. S., Battaglia G., Muma N. A., Van de Kar L. D. Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI // J Neurosci. : journal. — 2002. — November (vol. 22, no. 21). — P. 9635—9642. — PMID 12417689.

Serotonin receptors of the 5-HT 2C type also participate in oxytocin release. Stimulation of 5-HT 2C receptors leads to an increase in the level of corticotropin-releasing hormone ( CRH ) and vasopressin mRNA in the paraventricular nucleus and proopiomelanocortin in the anterior pituitary. In turn, restraint stress (which can cause depressive symptoms if it is chronic) causes secretion of prolactin, ACTH, vasopressin, and oxytocin, which is partly mediated by the 5-HT 2C receptor. Responses during such states as dehydration or hemorrhage cause oxytocin release through a serotonergic response that is partly mediated by 5-HT 2C:

1. Jørgensen HS (November 2007). “Studies on the neuroendocrine role of serotonin”. Danish Medical Bulletin. 54 (4): 266–88. PMID 18208678.

2. Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, Yeo GS, O’Rahilly S, Colmers WF, Elmquist JK, Tecott LH (June 2007). “Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation”. The Journal of Neuroscience. 27 (26): 6956–64. doi:10.1523/JNEUROSCI.2584-06.2007. PMC 6672238. PMID 17596444.

Cloninger (1995) and others (Netter, et al., 1996, Ruegg, et al., 1997, Gerra, 2000), by the end of the 20th century, were able to add newer information about serotonergic and dopaminergic antagonisms. According to this updated conception, high serotonin production causes behavioral inhibition and avoidance, which are traits of the authoritarian personality, whereas anti-authoritarian personalities tend to have a “novelty-seeking” type, with a high dopamine level and low serotonergic functioning. It is precisely this “novelty-seeking” type, anti-authoritarian and dissatisfied with the existing order of things, that is associated with reduced serotonin (and simultaneously - elevated dopamine), and it is precisely this type that is characterized by elevated “global-worldview” and philosophical interests:

1. Psychoneuroendocrinology 25: 479-496, 2000. Neuroendocrine correlates of temperamental traits in humans, Gerra G, Zaimovic A, Timpano M, Zambelli U, Delsignore R, Brambilla F.

2. Pharmacol Biochem Behav. 1981 Jun;14(6):773-7. Brain serotonin metabolism in hibernation. Popova NK, Voitenko NN. Biol Psychiatry 42: 1123-1129, 1997, Clomipramine challenge responses covary with Tridimensional Personality Questionnaire scores in healthy subjects, Ruegg RG, Gilmore J, Ekstrom RD, Corrigin M, Knight B, et al.

3. Neuropsychobiology 1996; 34:155-165, Serotonin and dopamine as mediators of sensation seeking behavior, Netter P, Henning J, Roed IS. Comp Biochem Physiol C Toxicol Pharmacol. 2002 Dec;133(4):507-13.

4. J. Psychol Neuropsychiatr Vieil. 2010 Dec;8(4):243-54. [Personality and risk of dementia]. [Article in French] Clément JP, Teissier MP.

5. Nature Medicine 1995, 1:623-625. The psychobiological regulation of social cooperation, Cloninger CR. JAMA. 1962 Jul 28;181:318-21. On migraine headache: serotonin and serotonin antagonism. Dalessio DJ.

Thus, interest in philosophy should correlate negatively with serotonin in the CNS. The difference between profiles of PHILOSOPHICAL INTERESTS and socionic profiles of GOOD MEMORY (previously considered by us here: vk.com/wall-168821911_45534 ) is that although serotonin is reduced in both cases, memory primarily requires high acetylcholine (and this is a typically “sensory” neurotransmitter, and in the case of memory it produces an elevation of the sensing pole). However, for PHILOSOPHICAL INTERESTS, with the same reduced serotonin, what should be characteristic is by no means “sensory” high acetylcholine, but high dopamine, and this produces the intuition pole for philosophical interests.

It is precisely all of this that we observe in the socionic profiles of both memory and philosophical interests. At the same time, characteristic markers of reduced serotonin (the poles of process, merriness, foresight, and Questimity) are present in the profiles in both cases.

LOVE OF COMPLEXITY

Another marker of reduced serotonin.

This is the property that in psychology is often called the bipolar cognitive style: COGNITIVE COMPLEXITY - COGNITIVE SIMPLICITY.

Its theoretical justifications are the same as those considered in the posts on philosophical interests ( vk.com/wall-168821911_45618 ) and good memory ( vk.com/wall-168821911_45536 ). Profiles of attraction to complex information represent a certain averaging of the profiles of philosophical interests and good memory. In all these cases low serotonin is important (so that it does not interfere with a sufficiently high level of neurotransmitter activity of acetylcholine and dopamine in the prefrontal cortex). However, for philosophy dopamine in the PFC is more important, and hence – the intuitive pole; for memory acetylcholine is more important, and hence – the sensory pole; whereas for the STRIVING FOR COMPLEX INFORMATION considered here, both are important (that is, both speed of thinking and high selectivity of associations, which depend on acetylcholine, and the striving for novelty provided by dopamine). Hence – ambiversion on the intuition-sensing trait. But everything else that is basic and characteristic of reduced serotonin is, as always, in place (primarily, the poles of process and foresight, as well as merriness)

Property:

NO STRIVING TO MINIMIZE ANY INFORMATION, TO REDUCE AND SIMPLIFY IT. No striving to avoid intellectual complexities. On the contrary, is drawn to complex information, to in-depth examination of everything; likes complex mental analysis that penetrates into the essence and interrelations of phenomena.

1. I like to complicate everything I work with, creating deviations from the customary norm. 0.87

2. Which motto is closer to you? 1) Everything is simpler than it seems. 5) Everything is more complex than it seems. 0.80

3. Which is closer to you? - 1) I do not like situations in which information is contradictory. 5) I like working through contradictions. 0.74

4. What more often irritates you in another person’s style of approaching problems? (indicate in the box on the right the number of the more appropriate option): 1) The tendency to complicate everything. 5) Oversimplification. 0.72

5. I do not like complications. Everything true should be simple. -0.94

6. I think more often about the coming week than about what will happen to the world in three years. -0.93

7. It is true that I do not like excessive overthinking around anything. -0.91

8. I do not like problematic subjects; in company I prefer discussing things that are simple and clear to everyone. -0.87

9. I believe in simple solutions - other people often complicate everything unnecessarily. -0.86

10. I do not like it when people around me begin to complicate something instead of making it simpler. -0.85

11. I like to simplify everything I work with, up to achieving unity of views among many people through the simplest things that are understandable to everyone.. -0.81

12. I like simplifying life around me, making it more balanced. -0.81

13. In the process of cognition, I prefer bringing all existing explanations into equilibrium rather than, on the contrary, looking in them for such points that disturb this equilibrium and ultimately lead to more complicated explanations. -0.79

14. I do not particularly trust Einstein’s theory of relativity and am inclined to listen to its authoritative critics. -0.77

15. I more often strive to simplify rather than complicate the structure of the object of my thought. -0.72

16. I do not read long texts consisting of many paragraphs on Internet forums at all - if a person does not want to fit their thought into a few lines, then there is certainly no point in reading them either. -0.59

Thus, the cognitive-complexity style is characteristic of reduced serotonin. Its principal markers on socionic profiles are high poles of process, merriness, democracy, and foresight. Conversely, preference for the “cognitive simplicity” style is associated with the poles of result types (“left”), the “serious,” “aristocrats,” and the “carefree.” The neurophysiological basis of the cognitive-simplicity style is a certain weakness of cholinergic and dopaminergic mediation in the prefrontal cortex and other key brain structures caused by excess serotonin, which leads the subject toward “economizing” intellectual resources.

Let us recall two more clusters that likewise tend toward increased “restless” intellectual activity and are obviously associated with the increase in cholinergic, dopaminergic, noradrenergic, and glutamate neurotransmission in the principal “mental” structures of the brain caused by REDUCED SEROTONIN, and with the reduction there of conformist oxytocin activity:

LIVES NOT ONLY “HERE AND NOW,” BUT IS ALSO INTERESTED IN THE MEANING OF WHAT IS HAPPENING, QUESTIONS OF WHERE AND WHY, THE PURPOSE AND PROSPECT OF THE DEVELOPMENT OF EVENTS

1. I often ask myself: - What next, and what comes after that? 0.86

2. I am constantly asking myself some questions internally. 0.81

3. I always keep something unfinished and contradictory in mind - because without a prospect, without something open and unfinished, I find life boring. 0.81

4. I constantly think about the meaning of life. 0.77

5. I often become completely immersed in reflection. 0.77

6. I often (apparently, more often than others) ask myself questions internally about the meaning of what is happening. 0.75

7. In my memories of the past, alongside events that actually happened, there are always (more than half) also plot versions - how everything could have happened and developed then, if only this or that had occurred… 0.73

8. I constantly ask myself some questions internally; I cannot live entirely without problems. 0.73

9. I like science fiction about social utopias or dystopias, that is, about different versions of how society might be organized. 0.68

10. The absence of meaning in my life is painful for me. 0.67

11. I am very interested in what will happen to the world a hundred years after I am gone. 0.56

12. In communication I almost always look for the reasons that make people speak and act one way rather than another. 0.51

13. I live “here and now.” -0.94

14. I live in the immediate present moment. -0.92

15. I live in the present moment. -0.84

16. It is more pleasant for me when people around me rate highly: 1) The prospects of my undertakings 5) The current result of my undertakings -0.82

17. I always easily put a full stop to each successive task once I have achieved the required result. -0.70

18. I am bored by books involving all kinds of “historical” fantasy, as well as by books with various inventions about alternative pasts and futures. -0.68

19. The advancement of society is not especially important to me - there are more important values. -0.68

20. I think about what will happen tomorrow or the day after tomorrow with much greater pleasure than about what will happen in a year. -0.64

21. I am indifferent to other people’s successes and the secrets of those successes; I usually have no interest at all in comparing myself with them or ferreting them out - I live my own life. -0.48

DISSATISFACTION WITH WHAT IS ALREADY POSSESSED AND WHAT ALREADY EXISTS. Fault-finding (including toward oneself, one’s own qualities). Protest reactions, striving to improve and perfect everything one has and everything around oneself. Likes to register and think over emerging problems.

1. I sometimes have a carefully concealed feeling of inferiority and depression - because of thoughts that I do not meet the high demands I myself place on my life. 0.90

2. As far as I am concerned, the world is arranged completely unlike the way it ought to be. 0.89

3. I often feel inner indignation about various aspects of the life around me. 0.87

4. I often feel a certain inner protest, disagreement, within myself. 0.84

5. I sleep too much. 0.80

6. In my soul I often feel some burning protest in connection with something. 0.80

7. There is much that is bad in me, things that could be regarded as shortcomings. 0.78

8. Political disagreements can quite well cause a family to break apart. 0.75

9. I often experience a feeling of protest internally. 0.74

10. I want to change and improve the surrounding order. 0.71

11. I am better than others at recognizing an approaching problem where others see only a smooth surface for a long time. 0.69

12. I have an obsessive habit of constantly evaluating and checking myself. 0.54

13. At least once a month or more often, I read some novella or novel. 0.49

14. I am easily irritated by mistakes in my work that I made myself. 0.48

15. I constantly want to acquire new knowledge. 0.46

16. I am generally satisfied with the way the world is arranged. -0.94

17. I usually do not keep inconvenient and unpleasant thoughts and conjectures in mind for long and easily drive them out. -0.90

18. I do not understand people who see and find some kind of “problems” in everything. -0.88

19. I easily adapt to any social changes. -0.88

20. I fully accept myself as the person I am. -0.87

21. I am satisfied with my position in society. -0.86

22. Compared with many others, I am more satisfied with what already exists. -0.85

23. My mood is normal now and I have no more problems than usual. -0.84

24. It is true that among the people I know there are none whom I sincerely and deeply hate for their views. -0.83

25. I usually defend the existing realities of the surrounding world against critics because I find more merits in them, whereas they see only shortcomings. -0.82

26. I know how to accept everything life gives with gratitude and without disgusted grimaces. -0.82

27. The surrounding world is quite satisfactory. -0.81

28. One must know how to enjoy any life; I do not understand those who almost all the time keep a “fig” in their pocket. -0.77

29. More harm comes from those who are: 1) Satisfied with everything. 5) Dissatisfied with everything. -0.73

30. My dissatisfaction is almost always caused by the actions of specific people rather than by the course of life as such. -0.71

31. I do not strive to rethink something that already works satisfactorily. -0.69

32. I am quite satisfied with all my talents and abilities. -0.64

33. I myself never recall past mistakes, and I will not burden others by reminding them of them either. -0.55

The principal markers of reduced serotonin (in the form of the poles of process, merriness, foresight, Questimity) are evident for both properties under consideration.

RUMINATION OF THOUGHTS (“MENTAL CHEWING GUM”)

Another cluster associated with weak serotonergic inhibition of dopaminergic neurotransmission in the prefrontal cortex. An additional factor in this property may also be a deficit of GABA inhibition due to insufficient serotonergic influences (here vk.com/wall-168821911_45536 we considered the reason for the correlation between the functioning of serotonin and GABA, namely that SEROTONIN activates inhibitory GABA neurons through its excitatory 5-HT6 receptors located on the bodies of these neurons, and thereby enhances the operation of inhibitory GABA neurons).

RUMINATION OF THOUGHTS, WEAKNESS OF THOUGHT INHIBITION (much dopamine activity, little serotonin and GABA activity). Long chains of thoughts without breaks; thoughts are not interrupted, but link one after another. Intrusive thoughts (ruminations) are frequent and difficult to displace even consciously. Neurophysiologists associate rumination with hyperactivity of the medial PFC (especially - with hyperactivation of the anterior part of the cingulate gyrus, ACC) and other regions of the brain’s default-mode system. An excess of dopamine activity in the mesolimbic pathway is often noted in this context, although dopamine activity in the mesocortical pathway may also be reduced.

1. I often “immerse myself” in the future, indulging in dreams, hopes, or fears. 0.96

2. Sometimes I simply cannot distract myself from some anxious fantasy. 0.93

3. I often indulge in mental games in which my imagination runs away into other invented worlds. 0.88

4. My imagination often dominates me. 0.87

5. As a child, when playing various games, I liked talking to myself. 0.86

6. I often cannot drive away some thought that sounds insistently and loudly in my head. 0.86

7. I often have repetitive, constantly recurring intrusive thoughts (so-called “mental chewing gum”) that are almost impossible to get rid of. 0.86

8. Sometimes during the day I bring up the same thought many times in succession. 0.86

9. Internal “pictures” in my head almost always dictate what around me will enter the sphere of my attention and what will fall outside it. 0.84

10. Almost every day it happens that I mentally imagine myself in someone else’s place and mentally play out situations. 0.84

11. There are things (thoughts, experiences, symbols) on which I constantly become “stuck.” 0.84

12. I often recall in detail conversations and dialogues in which I participated many weeks or even many months ago. 0.82

13. I often have intrusive, repetitive thoughts, including in the evening - because of which I cannot fall asleep for a long time (sleep does not come). 0.81

14. I have intrusive thoughts that are difficult to leave and relinquish because of their now habitual pleasantness. 0.80

15. Many characters are simultaneously present in my thoughts. They talk there, move, and live their natural unpredictable lives, while I merely observe them from the outside as though I were sitting in a theater. 0.77

16. At times I am pursued by loudly sounding intrusive thoughts accusing me of sinful behavior. 0.76

17. It is as though there is a permanently pressed reset button in my head that continuously loads the same thoughts, even if I try to get rid of them. 0.76

18. Every hour or so, in my thoughts I “run ahead,” turning over versions of events that have not yet occurred. 0.76

19. I like reflecting on all kinds of hidden meanings. 0.75

20. In some situations I am characterized by compulsively repetitive behavior. 0.73

21. I have some frequent and intrusive memories. 0.72

22. Intrusive memories of the past often emotionally “suck me in.” 0.70

23. During the day, I usually at least once (and sometimes several times) enter states in which one feels a certain extraordinary importance of the current moment, the swiftness of all thoughts, the saturation of every second with energy and mobilization of forces, and at the same time it often seems that one is standing on a narrow ridge between one’s own great triumph and deep panic. 0.68

24. There are states in which any thought that comes to mind immediately begins to seem supremely important, supremely significant to me. 0.66

25. Thoughts and assumptions often come to mind on the slightest pretexts. 0.63

26. Becoming immersed for a long time in dreams and fantasies about something is completely unlike me. -0.91

27. During the day I never daydream in any fantasies; if I have them at all, it is only before sleep, when I am already falling asleep. -0.87

28. My imagination is fairly responsive, but it never becomes intrusive for me. -0.85

We continue the flash mob on clusters of reduced serotonin. We remind the reader that increased intellectual activity is associated with a high status of excitatory neurotransmitters (acetylcholine, dopamine, noradrenaline, glutamate). The negative role of serotonin with respect to intellectual activity is caused by the fact that, through its receptors of the 5HT-1A and 5HT-2C types, it either directly inhibits neural conduction in cholinergic, dopaminergic, noradrenergic, and glutamatergic neurons (reducing the release of their transmitters into synapses), or does so through inhibitory GABA interneurons, which, by contrast, are activated through serotonin receptors of the 5HT-6 type on the bodies of these inhibitory interneurons (see the literature review on all this in the posts vk.com/wall-168821911_45475 , vk.com/wall-168821911_45536 , vk.com/wall-168821911_45618 .

INTELLECTUAL ACTIVITY, HIGH INTELLECTUAL AMBITION, avoids a philistine way of life, trivial solutions, views, and beliefs; gravitates toward complex tasks, toward increased concentration of information received and processed (especially verbal second-signal information, including sociopolitical information). A cognitive-complexity style with a bias toward logic.

1. Knowledge of economics, science, and politics can help in making decisions in everyday life. 0.89

2. When another person has annoyed me, I want to analyze the situation and immediately state my considerations to that person aloud point by point. 0.86

3. When I read a collection of stories and novellas by different authors, I very much want to assign a score to each story immediately, right there in the book. 0.86

4. When I read articles on the Internet, I am always interested in the tables of numerical information presented in them. 0.86

5. Since my school years I have been more well-read and erudite than others. 0.81

6. My intelligence is higher than that of most acquaintances. 0.80

7. If choosing a TV program among a sports program, a romantic film, or a documentary, I would choose the latter. 0.80

8. I always strive for a comprehensive analytical examination of an object or phenomenon in order to answer the questions: “why?”, “for what purpose?”, “what for?”. 0.80

9. I almost always try to obtain the information I need from several parallel, independent sources. 0.79

10. I often reason about politics and leadership. 0.77

11. The capabilities of my mind are limitless - I like reasoning, displaying my intellect, showing myself in some interesting discussion. 0.76

12. I often think about shortcomings of legislation and existing rules and arrangements. 0.74

13. I like watching films about the history of science on television. 0.74

14. At school I was distinguished by a good memory for exact dates of various battles and other events that were supposed to be known in the national-history course. 0.70

15. Jokingly speaking, I am a “news addict”; I always watch all news broadcasts on TV or listen to them on the radio with great interest, even repeats. 0.67

16. I remember many kinds of specific facts - any small detail will come in useful someday and may become a key to understanding something important. 0.67

17. I retain in memory most facts I hear. 0.67

18. I easily find flaws in my work and repeatedly postpone the final stage in order to correct what has already been completed. 0.63

19. The highest calling of a person is to add to society’s storehouse of well-known facts and knowledge. 0.62

20. I have always been interested in the laws governing the development of society and civilization. 0.61

21. I often save interesting information from news websites on my computer (almost every time I visit news feeds). 0.59

22. I like checking texts and searching them for small defects and errors. 0.57

23. I have a talent for teaching. 0.55

24. I like watching news broadcasts on television or the Internet (major world events) 0.53

25. I like watching television programs with discussions assessing one or another past historical event. 0.51

26. As a rule I begin to become bored and irritated by discussion of any logical contradictions. -0.85

27. I often fail to notice causal relationships between events. -0.82

28. I quickly tire of excessively “smart” and serious conversations. -0.81

29. It is true that I find it rather boring and uninteresting to compare details of different objects and search for patterns common to them. -0.80

30. I am not inclined to watch scientific or documentary films on television or read articles about science on the Internet and in magazines. -0.79

31. When I am in trouble, I focus more on catching and “comprehending” the overall holistic feeling from everything that is happening than on analysis. -0.79

32. My interest in scientific questions is fairly superficial; in any case, I would not choose a profession in this or a purely technical field. -0.78

33. It is true that when elections take place, I am not interested in comparing the results across individual electoral districts. -0.77

34. I will not listen to a person’s opinions and advice if they are presented in a disrespectful manner. -0.76

35. I usually become irritated when I am asked to justify something. -0.76

36. Psychology should be based mainly on an individual approach rather than dividing people into categories, and therefore - attaching labels. -0.73

37. Sincere faith is more often more valuable than knowledge. -0.72

38. I am almost always irritated by conversations about anything unaesthetic. -0.70

39. When I buy a new device, I usually do not read its instructions completely and very carefully. -0.69

40. Problems at the level of family and the collective interest me more than problems of society. -0.65

41. I often ask questions, but do not like answering and formulating anything. -0.64

42. I very rarely read Internet articles about new technologies. -0.63

43. I attend church services. -0.62

44. I would like working as captain of a river tugboat more (in terms of the content and character of the work) than working as a computer-repair technician. -0.62

45. I believe in psychics. -0.61

46. My principle is: “the less you know, the better you sleep.” -0.61

47. I think I would very much enjoy working in a charitable foundation providing assistance to sick children or needy artists and teachers. -0.61

48. Faith stands above any doubts for me. -0.59

49. A reliable person should be able to believe sacredly, without questioning or reasoning. -0.59

50. If advice is given in a rude form, I do not need such advice. -0.59

51. I greatly value and respect people’s good luck. -0.59

52. I believe that authority should rely not on the elite but on ordinary people - very ordinary people at that. -0.58

53. Another person’s ethical argument is more likely to make me do something than another person’s logical argument. -0.58

54. If you were engaged in charity in poor African countries, what would you prefer to invest money in? - 1) Programs to limit and control the birth rate. 5) Reducing child mortality. -0.57

55. I have absolutely no interest in the surnames and life histories of those who led the country in the previous century. -0.57

56. I have often fallen asleep while trying to follow a lecturer’s train of thought. -0.56

57. As a rule I am irritated by people who like displaying their erudition. -0.56

58. When contemplating a flickering flame and flowing water, against that background I more often experience pleasant thoughtlessness than have any thoughts arise. -0.56

59. Absolutely all people FOR WHOM I WOULD BE READY TO MAKE A SERIOUS SACRIFICE are people I know personally and closely or relatives (there are no public figures whom I do not personally know among them at all) -0.56

60. It is difficult for me to memorize while studying. -0.53

61. In my thoughts, I more often formulate for myself WHAT must be done rather than HOW it can be done. -0.49

62. A bad person will never convince me of anything, even that two times two equals four. -0.46

The final profiles of the property show high indicators of logic (which is unsurprising), as well as markers of REDUCED serotonin that, judging by all the clusters considered previously, are now obviously characteristic to us: elevated poles of process, foresight, merriness, and Questimity.

The almost neutral balance on intuition-sensing shows that both high acetylcholine activity and high dopamine activity are almost equally important for this property (at least in the prefrontal cortex; as for acetylcholine activity – surely also in the interhemispheric cholinergic collaterals, through which rapid information exchange takes place between structures of the brain hemispheres)

INVETERATE DEBATER, intellectually self-confident and inclined toward demonstrative intellectual dominance in relationships.

1. I am inclined toward disputes and confrontations. 0.97

2. If I play some game with someone, I like to set all kinds of conditions of my own. 0.89

3. I like arguing on a wide variety of topics; in doing so I am inclined to become heated and spoil the mood for myself and those around me. 0.89

4. I blurt out answers before I have heard the question to the end. 0.89

5. If there is an opportunity to make those around me understand my superiority, I will not fail to do so. 0.88

6. I often give others instructions, but I myself cannot stand a commanding tone. 0.88

7. I try to impress those around me with my knowledge and show them my superiority, but at the same time I never disclose the sources of my information - let them wonder whether I invented all this myself. 0.86

8. If I am interrupted in a conversation, I invariably first try to complete the statement of the thought I have already begun, fully and to the very end, without allowing myself to be stopped, and for this purpose I warn the interlocutor with gestures or increase the volume of my voice. 0.83

9. My speech often uses words reflecting the certainty of something. For example: certainly, undoubtedly, unquestionable, distinct, most pronounced (with respect to some trait), etc. 0.81

10. I often speak of my assumptions as accomplished facts. 0.80

11. I very rarely have a desire to object and argue. -0.86

12. I am afraid to raise any mutual problems in communication; it is better to avoid both them and the possible conflicts associated with them. -0.85

13. From shyness in communication my face sometimes becomes covered with red blotches. -0.83

PERCEIVES AND CONSIDERS ANY SITUATION IN PARTICULARS, DETAILS, AND SPECIFICS, RATHER THAN ONLY IN GENERAL AND AS A WHOLE.

The property closely overlaps with the psychological division into cognitive-complexity and cognitive-simplicity styles and, in essence, characterizes the difference between intellectual activity with reduced serotonin and a certain intellectual laziness with elevated serotonin (and from this, in the case of laziness, – arise simplification of tasks and reduction in the number of details and objects considered).

1. In the domain of facts I always proceed from the particular to the general; I always investigate details and small particulars first. 0.82

2. I characteristically and habitually keep very careful account of all small details in the sequence of carrying out some undertaking. 0.81

3. In my work I personally delve into every detail and never lose sight of small particulars. 0.80

4. I begin solving problems by collecting and clarifying all details and particulars. 0.77

5. The world is built on particulars - therefore I am always very attentive to the small details of this world. 0.78

6. I am very sensitive to small facts that remain unnoticed by many other colleagues. 0.76

7. I am usually very zealous about the detailed precision of carrying out what I have conceived, and I never entrust executors with “creative freedom.” 0.75

8. A holistic picture of an event or object takes shape for me only after I have gathered many small facts and studied all the individual details. 0.72

9. I am best at some kind of “fine” work based on small details and nuances. 0.70

10. I have almost eidetic visual memory - with my eyes closed I can imagine an image I have just seen with many details and particulars. 0.71

11. I am very sensitive to small facts or legal details that remain unnoticed by many other colleagues. 0.70

12. I am an excellent “finisher” - I like constantly refining the quality of work in its details and bringing familiar technologies to perfection. 0.69

13. In any undertaking I am attracted by details and nuances that are scarcely noticeable to others. 0.67

14. I have very detailed perception - even if I look at an unfamiliar person, I see not a face in general but a specific face with all its particulars; I notice wrinkles, the shape of the lips, hairs in the wrong places, small abrasions, etc. 0.67

15. I have a habit of repeatedly rechecking myself. 0.65

16. I easily recognize an object even from its individual details. 0.64

17. I like precision, concreteness, and detail in everything. 0.62

18. I prefer detailed classifications in which the objects being sorted are divided into many groups taking subtle particulars of their properties into account. 0.59

19. I can easily picture the faces of people I know in my mind - with all the details and particulars 0.56

20. In the course of any undertaking I notice many of its small details, by which I am involuntarily distracted. 0.32

21. My attention likes switching among numerous details and particulars in my surroundings. 0.28

22. Over the course of a long conversation I remember perfectly all its turning points and details, all the interlocutor’s main phrases. 0.24

23. I prefer broad classifications without small details and refinements. -0.88

24. I like professions and activities in which quality is assessed more by an overall holistic and unified impression than by specific details. -0.87

25. Seeking to obtain a result sooner, I often deliberately ignore small details of the process - better a nonoptimal but timely solution, because afterward I will in any case replay and refine everything again. -0.86

26. I am attracted by ideas that are new and large-scale; I am always ready to leave details and particulars to others. -0.85

27. In the domain of facts, I do not waste time analyzing details but immediately try to discern the general, global trend and regularity. -0.83

28. In work I usually neglect details and focus only on the principal challenges. -0.77

29. In work I do not like “cleaning up details”; I leave that to others. -0.74

30. I cannot stand any concreteness and detailing - an overall impression is usually enough for me. -0.75

31. I perceive the reflection of experiences on people’s faces more immediately and as a whole, without examining individual details. -0.74

32. At the first cursory visual glance at a situation, I immediately notice the whole, the “overall arrangement,” whereas many visual details are not noticed and are entirely missed by me. -0.70

33. It is difficult and tiring for me to switch attention frequently among small details. -0.68

34. Inconspicuous details do not attract me; I rather like everything outstanding, bright, large, and striking to the imagination. -0.67

35. I usually perceive and understand any situation immediately and as a whole, without separating out its component parts for better understanding and initially without even thinking about them. -0.67

36. I usually think about phenomena that interest me on a large scale, with half-erased details. -0.64

37. When looking at an object, I catch the overall sensation from it and perceive its image as though immediately as a whole - without needing to examine individual details specially. -0.62

38. I am much more concerned with global matters than details. -0.63

39. A large-scale whole is always more interesting to me than its small and “fine” details. -0.62

40. A multitude of details and small particulars tires me - I do not like switching attention frequently. -0.58

41. I have “large-block” logic: I instantly notice important facts and as a rule ignore small details. -0.51

42. I avoid small and detailed classifications; I usually prefer dividing objects into several broad groups. -0.39

The next two properties – the “GRAMMAR NAZI” CHARACTER and the “NEED FOR DETAILED ANALYSIS” – both border in their meaning on both the cognitive-complexity style and thought rumination within OCD, which are characterized by a tendency toward reduced serotonin. Therefore, alongside them, these too can be regarded as, if not the strongest, nevertheless still markers of reduced serotonin that tend toward the group of properties of increased intellectual and mental activity:

“GRAMMAR NAZI” PROPERTY - increased demands for verbal, terminological, and factual precision

(another cluster within the group of properties of increased intellectual activity and the cognitive-complexity style, likewise directed toward demanding attention to details and small particulars).

1. I am told that I can be excessively tedious in my persistent pestering when I want to obtain some clarification about a situation. 0.90

2. I always demand that any assertion be confirmed by a reference to a source. 0.89

3. I am usually more zealous than my colleagues about terminological precision - if something is called exactly that, then it must correspond to it completely. 0.88

4. When solving a problem, I practically always try first to check and clarify the reliability and authority of the data provided. 0.87

5. “Remain calm and be so good as to express yourself in proper literary Russian” - this is a frequent demand of mine toward another person with whom I have to communicate. 0.82

6. I will abandon a book and not read it, whatever it may be, if I find a spelling mistake in it. 0.66

7. When I study a language, its grammatical rules interest me already at the early stages. 0.63

8. Does the “incorrectness” of the grammatical construction of the following phrase irritate you: “This is his job. To feed his family. To live.” 0.13

9. When writing, I often carelessly omit necessary punctuation marks after words. -0.52

Likes to analyze everything, classify, clarify in detail, and put things into orderly categories:

1. I willingly organize and analyze what I encounter. 0.96

2. I am always attentive to the smallest logical details. 0.94

3. I like sorting all kinds of “heterogeneous” information into categories. 0.93

4. I enjoy painstaking scientific-research and analytical work involving analysis of complex phenomena and objects. 0.93

5. I like putting everything into orderly categories in order to understand better how the world is arranged. 0.93

6. I have good analytical thinking and strong logic; I like generalizing facts and understand diagrams, classifications, and structures well. 0.92

7. I am objective and sharp in judgments and principled evaluations; structures, classifications, concepts - that is my style. 0.91

8. At times I collect and systematize various curious factual data without any immediate specific purpose, simply for reserve and pleasure. 0.91

9. I am a broadly erudite person with a refined, rigorously analytical mind. 0.90

10. By my abilities I am a good logician and analyst. 0.89

11. I always strive for a comprehensive analytical examination of an object or phenomenon in order to answer the questions: “why?”, “for what purpose?”, “what for?”. 0.89

12. My favorite questions are: Is this arranged correctly? Does this fit into the existing system or fall outside it? 0.88

13. When I read articles on the Internet, I am always interested in the tables of numerical information presented in them. 0.88

14. When another person has annoyed me, I want to analyze the situation and immediately state my considerations to that person aloud point by point. 0.87

15. If something worries me, I immediately begin analyzing all the individual aspects of the situation. 0.86

16. I have always liked systematizing collections and sorting small objects, details, and facts according to some criterion. 0.85

17. If I were buying a computer, I would definitely want to know exact information about hard-drive capacity and processor speed. 0.85

18. I like “putting things into orderly categories,” organizing, and classifying. 0.83

19. Everything around me is clearly arranged “into orderly categories” in my memory and is retrieved from there accurately and without problems.. 0.83

20. As a child I liked systematizing collections. 0.82

21. I easily assimilate all kinds of news and analytical information by ear. 0.77

22. In my work I am distinguished by meticulous precision; I do not simply take anyone at their word, but check everything - both my own work and especially that of others. 0.76

23. When I am in trouble, I focus more on catching and “comprehending” the overall holistic feeling from everything that is happening than on analysis. -0.88

24. I very rarely read regulatory documents attentively. -0.72

25. A large variety, the “heterogeneity” of information that has to be sorted, as a rule quickly makes me tired. -0.70

Our plan for working with serotonin markers is as follows.

1. Finish considering the group of low-serotonin clusters associated with increased intellectual activity (we ourselves are already rather tired of them, but we need to finish – several more remain). We remind the reader that serotonin, through its receptors, inhibits neurotransmission in neurons with excitatory neurotransmitters – acetylcholine, dopamine, noradrenaline, glutamate, - and through this both “cuts off thoughts” and simply reduces the speed of thought processes overall. In addition, also through its 5HT-6 receptors, which are numerous on inhibitory GABAergic interneurons, it stimulates these inhibitory neurons, which in turn inhibit neurotransmission along chains of neurons. For all these reasons serotonin is synergistic with GABA, and both are inhibitory transmitters.

2. Then consider the next group of clusters associated with serotonin. These are those in which serotonin suppresses a person’s ambition. Low serotonin – is when goals have not been achieved, dopamine is high, one wants many things, dissatisfaction is high, motivations are strong. This includes envy and dissatisfaction with one’s existing social status. High serotonin, by contrast, – is when what was desired has been obtained, the achieved status appears satisfactory, and a strategy of conquest is replaced by a strategy of defending and preserving. Rationality and the striving to maintain the existing order of things increase. In monkeys, the higher the achieved status in the group hierarchy, the more serotonin rises. The most “creative” monkeys are low-status ones. When there is much serotonin - the level of contentment and satisfaction is high. When there is little - dissatisfaction is high, but creative activity is also higher. It appears that this works in humans as well.

3. Consider another group of serotonin markers. These are those in which serotonin works in conjunction with oxytocin (whose release it facilitates) toward greater trustfulness, good-naturedness, and prosociality of behavior. Low serotonin, by contrast, facilitates a distrustful, wary-negative attitude toward people. Impulsive aggression is also correlated with low serotonin.

4. Finally, there is another group of purely physiological correlates of serotonin that it is also advisable to consider. These are properties in which serotonin affects blood coagulation, nausea reactions, intestinal peristalsis, pain sensitivity, etc.

5. Based on consideration of all these cluster groups, we will construct a final averaged socionic profile of serotonergic activity, and will even try to play with individual types of serotonin receptors, attempting to estimate approximately their own socionic profile for the activity of each of them.

6. The socionic process-result trait (“rightness-leftness”) – is the trait that most often manifests itself in association with markers of serotonergic activity. We will definitely investigate how it happened that the purely formally introduced by Reinin socionic trait “Process-Result” came to such a pass that it turned out to be correlated with serotonergic activity. I hope we will examine this in detail. And it seems that by the end of the investigation we will clarify all the essentials. Perhaps we will come to the conclusion that there is nevertheless no strict identity between high serotonin and the result pole, and that in socionics the result pole (to a considerable degree - thanks to its name) simply accumulated the influence of all those factors where excessive divergent, spreading activity is limited (hence “result,” as a quintessence of economical informational concentration), whereas process – conversely, where excess is encouraged. Therefore, the result pole is associated not only with high serotonin (which limits activity), but also with elevated noradrenaline, which likewise “concentrates” a person’s activity on a narrow group of survival-related tasks and gives it a convergent character, narrowing into a tight focus. And process-result is also associated not only with neurotransmitters at all, but with conditions of early childhood that likewise affected the scope of the brain’s capacities, and hence its predisposition and very ability for excessive divergent activity.

THIS IS APPROXIMATELY OUR PLAN FOR FURTHER WORK (and at the same time - a clue to the course of the authors’ thinking in considering this entire topic)

And now let us consider another cluster and at the same time a marker of LOW SEROTONIN – still from the same group of clusters associated with increased intellectual activity:

IS INTERESTED IN THE NONPRAGMATIC SEARCH FOR “TRUTHS FOR THE SAKE OF TRUTHS”

1. The process of thoroughly investigating something useful often gives me even more pleasure than the stage of finally applying the result of the work. 0.81

2. My thoughts are most often about something large, global, uniting many things or many people at once. 0.81

3. When I read, I usually like the author’s lyrical digressions when in them the author speaks about something especially interesting and full of meaning. 0.78

4. What do you strive for more often? - 1) Eternal truth 5) Quick benefit -0.93

5. My main tasks in life, apart from family matters, are material well-being and comfort. -0.85

6. Local success here and now is more important to me than a sense of involvement in all affairs in the country or on the planet. -0.83

7. I do not care about the social system; I will arrange myself fairly well under any of them. -0.80

8. For it to be worth reading at all, any scientific article must necessarily be written technologically - that is, so that it reads as a single plot, without the need constantly to compare its different sections in one’s mind. -0.80

9. Knowledge must bring quick benefit; otherwise what the hell is it for. -0.79

10. For me, what matters most in any knowledge is that it be technological, readily applicable in the form of a sequential chain of actions. -0.79

11. New knowledge interests me only for achieving some goals, not simply for its own sake. -0.78

12. At school and university I mainly read only what could not be avoided under the curriculum. -0.78

13. In the process of cognition, I prefer bringing all existing explanations into equilibrium rather than, on the contrary, looking in them for such points that disturb this equilibrium and ultimately lead to more complicated explanations. -0.75

14. Compared with others, I am more often characterized by following ready-made patterns than by devising new methods. -0.73

15. As long as some method works overall, there is no point spending effort digging into it in order to improve it. -0.71

16. I like taking photographs of food I have prepared or eaten and sharing these pictures with friends. -0.69

WELL-DEVELOPED OPERATORS OF SPATIAL-LOGICAL RELATIONS IN THE PARIETAL CORTEX, including rapid and problem-free perception of the meaning of sentences with spatial-logical (logical-grammatical) relations (using the spatial prepositions above and below, concepts of higher-lower, left and right, mental spatial arrangement of objects, the sequence of cause and effect, relations of mutual belonging, asymmetrical-hierarchical relations among objects, etc.)

1. I have good spatial memory for the return route - after walking around an unfamiliar city to my heart’s content, I easily find my way back without asking passers-by for help. 0.87

2. I easily remember the spatial arrangement of city streets relative to one another and can without difficulty draw from memory a map of any familiar part of a city. 0.87

3. I easily notice characteristic landmarks in the terrain and, thanks to them, always remember the route well. 0.86

4. I orient myself very well in the surrounding space, as though its map were always in my head - with my eyes closed or in the dark I can easily walk around my apartment without bumping into anything. 0.86

5. I can easily draw a plan of my apartment from memory. 0.85

6. I easily reconstruct in my mind a holistic image of an object from some of its individual parts. 0.82

7. I remember many different distances - between cities, or to the center of the Earth, or to the Moon, etc. 0.80

8. When reading such expressions as “cousin’s mother,” “father’s brother,” “brother’s father,” “father’s mother,” I need no more than a second to understand clearly who is meant. 0.78

9. I can easily and without error divide or multiply simple fractions mentally within several seconds (for example, try mentally, without paper, dividing 15/16 by 3/4, then check yourself by written calculation). 0.61

10. I often confuse the order of necessary actions - which button to press first and which - afterward. -0.94

11. It is difficult for me instantly to figure out how “brother’s father” differs from “father’s brother.” -0.89

12. I often become confused about the required sequence of movements. -0.89

13. If I am asked to point with a pen at a pencil, I can easily become confused and point with the pencil at the pen. -0.85

14. Sometimes in explanations of how and where to go, I confuse the right and left sides. -0.85

15. Sometimes I confuse clockwise and counterclockwise directions of rotation and cannot always instantly determine exactly which way I need to turn. -0.85

16. Sometimes I become confused or take quite a long time to determine which side is left and which is right. -0.80

17. The strict order of words is often disrupted in my speech. -0.79

18. Sentences of the type “Petya is shorter than Vasya, and Petya is taller than Seryozha” make me think quite hard about who is taller than whom among the three - it is difficult to figure out mentally. -0.69

19. The globe and world map have never particularly interested me - and to this day I sometimes become confused about some world capitals and about where one country or another is located. -0.57

20. Sometimes I do not immediately grasp the meaning of phrases using expressions such as: “the son of the father’s sister,” “the wife of the uncle’s son,” etc. (it is difficult immediately to figure out who is meant). -0.57

21. In the phrase “the tiger was killed by the lion” it is difficult for me instantly to determine which of the two animals died. -0.48

Six more properties associated with development of the second-signal (auditory-speech) system, where the factor of low serotonin likewise has a positive effect on the level of abilities:

EASILY GRASPS THE MEANING OF OTHER PEOPLE’S LONG AND COMPLEX PHRASES WITH MANY SUBJECTS AND COMMAS.

1. By ear I instantly catch logical inconsistencies in other people’s speech. 0.85

2. I very rarely read regulatory documents attentively. -0.90

3. It is difficult for me to grasp the meaning of long and complex phrases or equally long and complex written sentences. -0.90

4. I perceive long sentences with many subjects and commas poorly. -0.87

DEVELOPMENT OF THE SECOND-SIGNAL SYSTEM AND AUDITORY-SPEECH CENTERS. Perceives information better “by ear” (which is associated with dominance of the left-temporal auditory center). Visual reading of phrases, as well as pronouncing them internally, is less effective for this person in terms of comprehending information. Therefore, even when reasoning with oneself, prefers to voice one’s thoughts aloud as well (for some reason, because of the excessively strong development of the left-temporal auditory area, this practice facilitates strengthening of the logical component of this person’s thinking - with right-hemisphere auditory temporal dominance, by contrast, it is easier for people to think “to themselves,” as well as to read information visually “to themselves”)

1. I usually express my thoughts willingly and at length. 0.79

2. When I begin to state my point of view, I sometimes find it difficult to stop. 0.78

3. When I walk with someone, I like talking along the way; walking in silence is uninteresting. 0.75

4. I like discussing aloud with someone the news I have heard or what I have read. 0.75

5. It is much easier for me to reach some conclusions if I reason with myself aloud rather than thinking silently to myself. 0.73

6. If I walk down the street with a friend, I often assess aloud the passers-by of the other sex whom we encounter. 0.69

7. I like reasoning aloud while focusing attention on individual details, even ones unrelated to one another. 0.66

8. I like explaining and clarifying things. 0.62

9. I have been told that in early childhood I began speaking very early - earlier than my toddler peers. 0.55

10. I would rather spend five days with my eyes blindfolded than remain silent and in absolute quiet. 0.54

11. I think much better if I immediately articulate my thoughts aloud. 0.53

12. In a conversation with an interlocutor I can reason aloud slowly and at length. 0.52

13. I like reasoning aloud. 0.44

14. I easily assimilate all kinds of news and analytical information by ear. 0.42

15. I often verbally accompany my actions (for example, when pouring coffee for guests, I comment aloud on what I am doing). 0.36

16. I can easily imagine with my “inner ear” how some person I know pronounces a long meaningful phrase in their characteristic voice. 0.22

17. By ear I quickly and without error catch all the thoughts that an interlocutor is trying to squeeze into their speech. 0.15

18. What first appears in your imagination when you hear the word “birds”? IMAGINE IT before reading further! HAVE YOU IMAGINED IT? If you first imagined their visual image, enter “1”. If you first heard their voices, cries, enter “5”. 0.08

19. During tense situations I “switch to hearing” - I begin to hear everything around me with heightened clarity and understand quickly. 0.08

20. When alone, I sometimes talk aloud to myself, that is, I say aloud what I am thinking about at that moment. -0.07

21. In my imagination there are many more words denoting something than visual images. -0.04

22. When I begin to reason logically aloud, I always know in advance what those arguments will ultimately converge upon. -0.03

23. In my thoughts I more often reason by means of words, inner speech, and sequentially at that, rather than in leaps or with the help of some vague visual “insights” and images. -0.02

24. It is difficult for me to perceive information by ear - the meaning reaches me slowly and is not grasped immediately (when visually reading what is written, it is much faster and easier). -0.61

25. I assimilate information better when I read it with my own eyes instead of perceiving it by ear. -0.57

26. I perceive information better with my eyes than with my ears. -0.56

27. I perceive information better visually than by ear. -0.46

28. I have problems with hearing. -0.46

29. I sometimes make mistakes in carrying out instructions because I incorrectly understand by ear exactly what I was instructed to do and what was wanted from me. -0.37

30. In a dimly lit auditorium I often involuntarily drift into a doze. -0.36

31. One of my ears hears much worse than the other. -0.28

32. In order to imagine the smell of a blooming rose or another flower, I must first visualize that flower before my eyes (without a visual image, absolutely no smell can be produced either). Check whether this is so. If it is, enter “5”. If you can imagine the smell of the flower from the name alone, without a visual image, enter “1”. -0.21

33. I remember the “tonality” and intonation of speech better than its content. -0.17

34. My thoughts make more use of visual images of varying degrees of clarity than of words. -0.12

35. It is difficult, almost impossible, for me vividly to imagine with my “inner ear” the living voices of my relatives, acquaintances, and friends - with their characteristic timbre, coloring, and intonations. -0.12

36. I remember people’s faces better than their voices. -0.06

DEVELOPMENT OF THE RIGHT-HEMISPHERE FRONTAL SPEECH AREA, DEVELOPMENT OF ITS CONNECTIONS WITH THE AUDITORY AREAS OF BOTH HEMISPHERES

1. I have very good intonational expressiveness of speech. 0.93

2. In my speech I usually “play” with intonation in a deliberately pronounced way. 0.92

3. In conversation my voice is usually strongly modulated by intonation - for example, I am better than others at reciting poetry “with expression.” 0.91

4. I know how to imitate another person’s manner of speech. 0.88

5. My voice has pronounced intonational modulation - I always emphasize the meaning of speech by raising and lowering pitch and changing its tempo and volume. 0.87

6. I am good at sound imitation - better than most of my acquaintances at imitating, for example, a cat’s meowing or a dog’s barking, a cow’s mooing, a rooster’s or some birds’ cry, a horse’s neighing, etc., something of that sort. 0.85

7. My speech often uses words reflecting the superlative degree of something. For example: outstanding, brilliant, awesome, great, enormous, fastest, tireless, etc. 0.83

8. I know how to and like to speak loftily and passionately about my feelings. 0.81

9. It is easy for me to imagine the voices of people I know. 0.81

10. I know many poems by different authors by heart. 0.80

11. I am excellent at telling stories. 0.78

12. I easily memorize a melody and can immediately hum it without errors. 0.76

13. When I tell something, my speech always contains many different descriptions and characteristics that I assign to someone or something using adjectives. 0.76

14. In my spare time I can accurately imitate the voice and intonation of a recent interlocutor. 0.75

15. By ear I instantly detect dissonances and “drifting out of key” in another person’s singing. 0.73

16. With my voice I can imitate another person’s intonation and manner of speaking quite well, down to characteristic features and the timbre of the other person’s voice. 0.71

17. It is true that I almost never make mistakes about the pitch of a musical note and can easily reproduce the sound of the required note with my voice or mental imagination. 0.68

18. By ear I can easily distinguish the musical note “C” from the neighboring note “D” (that is, even without comparison, hearing them individually, I will not confuse “C” with “D”).. 0.62

19. I am almost always constant in the volume of my voice, - sudden and strong raising of my voice, shouting, and yelling are absolutely uncharacteristic of me. -0.88

20. My speech is usually inexpressive and poor in intonation. -0.87

21. My musical ear is clearly worse than that of others. -0.85

22. Very often it is difficult for me to express my feelings in words. -0.82

23. My speech is poor and restrained because I often experience difficulty finding the right word - it is somewhere in my head but I cannot remember it, and I understand this, so I often repeat the same word several times or simply fall silent. -0.79

24. It is difficult for me to repeat (hum) a melody I have heard accurately - my musical ear is worse than that of many others. -0.78

25. My speech is logically very clear but rather dry; it contains many clarifying function words - prepositions, conjunctions, particles, introductory constructions. -0.78

26. It is true that I never speak aloud about my pain, fear, hunger, or fatigue, even if I experience them. -0.75

27. I have a certain natural inarticulateness - it is difficult to construct phrases quickly and smoothly (both orally and in writing). -0.72

28. From my intonation it is not always possible to understand whether I am asking a question or asserting something -0.64

29. It is difficult for me to find synonyms for a word (that is, to find in memory other words with a similar meaning). -0.64

High joint integration of the visual and auditory analyzers

1. Sounds are almost always associated with light and color for me, and conversely, memory of visual images is also always filled with sounds. 0.90

2. When listening to someone’s account, I imagine it mentally in concrete visual images. 0.65

3. If I listen attentively to an interlocutor, I hardly perceive them visually, and if I begin examining them attentively, I stop hearing and understanding what they say. -0.66

Smoothness and correctness, fluency and grammaticality of speech, its automatically correct construction without hesitations and difficulties in building a phrase, as well as rapid comprehension of meaning in other people’s phrases. Good functioning of the anterior Broca’s area, the parietal-lobe cortex, and the parietal lobule in the left cerebral hemisphere - no symptoms of Broca’s aphasia, orthographic aphasia (associated with dysfunction of the left parietal lobule), or conduction aphasia.

1. I have smooth speech, without needing pauses to find words, and when formulating thoughts aloud I never say “uh-uh” or “mm-uh” between words. 0.89

2. During a conversation it is very difficult to interrupt or stop me without allowing me to finish my thought. 0.87

3. My sentences are always perfectly smooth, without any hesitations in their oral construction and without any need for subsequent correction of word order in writing. 0.86

4. I am a good presenter; I know how to convey material to an audience briefly and clearly. 0.83

5. I have a very good sense of correctly constructed, smoothly flowing speech, a “feel for language.” 0.79

6. When I express myself aloud, my sentences come out somewhat awkward; it is not easy for me to translate an intention into an external, extended utterance. -0.94

7. I have difficulty formulating an utterance, translating my already-formed thoughts into extended speech. -0.93

8. When I am agitated, it is as though my “tongue sticks” - I lose the ability to express my thoughts effectively aloud. -0.91

9. I sometimes make mistakes in carrying out instructions because I incorrectly understand by ear exactly what I was instructed to do and what was wanted from me. -0.89

10. When expressing myself aloud and in writing, it is difficult for me to maintain the correct word order in a sentence, as a result of which the phrase often comes out confused and awkward. -0.84

11. I often fall silent in the middle of an utterance and continue only after a repeated “push,” a repeated request. -0.81

12. When I speak aloud, I often make “uh-uh-uh..” and “mm-uh-uh…” sounds while trying to find the right word somewhere “in the air.” -0.79

13. I have almost never managed to assimilate lecture material directly during lectures - at some point I would inevitably “drop out” of the explanation, and afterward I always had to assimilate the material again by reading the textbook and notes with my own eyes. -0.78

14. If I speak quickly, I produce fluent but confused speech, sometimes with meaningless insertions, because it is difficult for me to monitor my own speech. -0.76

15. The strict order of words is often disrupted in my speech. -0.72

HIGH LEVEL OF LITERACY IN SPEECH AND WRITING.

1. I always write absolutely correctly, without any errors. 0.88

2. I have “innate literacy” - for as long as I can remember, already from the middle grades of school, I have always written absolutely correctly, becoming confused neither in spelling nor in punctuation. 0.80

ON ENVY.

LOW SEROTONIN – MEANS HIGH AMBITION AND WEAK EMPATHY

High CNS serotonin activity is characterized by contentment with what one has, relaxation, low activity of aspirations, and reduced ambition.

Low serotonin activity is characterized by a high level and active presence of unsatisfied aspirations, dissatisfaction with one’s existing social status, and high motivation to raise it.

High serotonin production causes behavioral inhibition and avoidance of everything risky, dangerous, disgusting, and shocking; a tendency toward narrowing and convergence of motivations; and supports behavior directed toward preserving what one has.

A low serotonin level causes divergent (spreading) behavioral activity directed toward searching for the new and conquering new positions, with low fear of dangerous actions.

Under the influence of high serotonin, the range of what is perceived as fair and acceptable expands, while the inclination toward conflict behavior decreases. High serotonin increases yieldingness in negotiations, including with respect to unfair offers

Under the influence of low serotonin, by contrast, the range of what is perceived as UNfair and personally UNacceptable expands, and the thresholds for the emergence of conflict in behavior decrease. Low serotonin reduces the subject’s yieldingness in negotiations and facilitates an “all or nothing” tactic: “either I personally get more here, or we both lose; I don’t care.”

High serotonin reduces the motivation to do harm to others.

Low serotonin increases it.

High serotonin increases empathy.

Low serotonin is correlated with lower empathy.

High serotonin increases respect for other people’s interests

Low serotonin facilitates selfish manifestations

Upon obtaining what is desired, serotonin increases, and a period of calm contentment accompanied by benevolence toward others begins.

When stress arises, serotonin decreases, which is accompanied by increased selfishness and conflict, but also by higher exploratory and intellectual activity.

ALL OF THE ABOVE-LISTED THESES HAVE BEEN CONFIRMED IN MANY STUDIES, AND WE WILL SUBSTANTIATE THEM IN DETAIL IN THE LITERATURE REVIEW A LITTLE LATER.

For now, let us use these theses to state that LOW SEROTONIN is associated, in particular, with the following manifestations that are partly markers of it:

• Envy, enviousness from constantly comparing one’s own successes with those of others;

• A high level of unsatisfied aspirations, an elevated level of ambition;

• Increased motivation to raise one’s social status;

• Narcissism and contempt for ordinariness;

• Contempt for those of lower status, defense of principles of social inequality and social segregation;

• Hot-tempered impulsive aggression;

• Malevolent distrust and suspiciousness toward people;

• A tendency toward accusatory moralizing;

• A predisposition to “pull the blanket toward oneself,” to unfair decisions in one’s own favor.

And we will begin analyzing these and semantically related properties with ENVY:

Envy, enviousness from constantly comparing one’s own successes with those of others

1. I am often overcome by envy of someone. 0.83

2. I become jealous and begin to feel irritated toward guests whom my pets fawn over. 0.77

3. I envy my partners and gradually begin to feel spiteful toward them if they are luckier than I am in a card game. 0.76

4. I am sometimes tormented by envy of other people’s luck. 0.75

5. Another person’s success irritates me greatly, especially when fools are lucky. 0.75

6. At least once a month, it happens that I envy someone else’s attractive item of clothing that I do not have. 0.71

7. At times I find it difficult to restrain my envy. 0.69

8. I am outraged by people who cannot even dress decently but have more money than I do. 0.67

9. Another person’s luck in a game against the background of my temporary losses has often driven me to angry envy and almost to tears. 0.57

10. Sometimes I happen to feel the pangs of envy. 0.56

11. There are people whom I envy strongly. 0.55

12. At least once a week I envy someone else’s good fortune. 0.54

13. I often encounter envy of my intelligence and success. 0.51

14. If there is an opportunity to make those around me understand my superiority, I will not fail to do so. 0.47

15. Envy and rivalry are clearly not characteristic of me. -0.69

16. Enviousness, envy of someone - is completely alien to me and does not describe me. -0.63

17. I am a completely unenvious person - if someone is lucky, that is merely a fact, not a reason for envy. -0.57

HIGH LEVEL OF UNSATISFIED ASPIRATIONS, elevated level of ambition (a consequence of reduced serotonin)

1. Very often in life I find myself in a state of intense stressful tension, when all forces are concentrated and mobilized. 0.82

2. At times I react to minor offenses as though they were grave insults. 0.79

3. I tend to plan too much and worry excessively about the future; sometimes I become “stuck” on this. 0.79

4. I react very painfully if someone surpasses me in encouragement and awards. 0.75

5. Almost every day I think about the impression I make on others. 0.74

6. I often have fears that for some reason I may lose my status, lose my social identity. 0.74

7. I am very exactingly attentive to the details of how people behave toward me and how they regard me. 0.74

8. Thoughts about tomorrow are always interesting to me; they always call me somewhere, promise something, and have some immediate important significance for me, filling life with meaning. 0.74

9. I always experience it briefly but sharply if something does not work out or fails. 0.73

10. I am easily offended and often feel hurt. 0.73

11. It is very important to me how I look and how those around me evaluate me. 0.71

12. If I want to achieve some goal that elevates me, I can stubbornly pursue it for years. 0.70

13. I have an excess of motivation; I often find it difficult to stop working. 0.70

14. I am always concerned with raising my social status. 0.69

15. I always feel irritation if someone even jokingly hints that I lack harmony in clothing or supposedly have no taste. 0.69

16. I like planning my day, week, month, etc. 0.69

17. A situation in which I do not get what I want is unbearable to me. 0.69

18. Every day I immerse myself in thoughts about my plans for tomorrow. 0.68

19. I always feel strong dissatisfied irritation if life deceives my expectations and I do not get what I was counting on. 0.67

20. It is difficult for me to change goals, even if they seem too difficult or impossible to accomplish. 0.66

21. I always experience it very painfully when some desire of mine remains unsatisfied or is not fully satisfied. 0.66

22. I am jealous of those who become the center of attention in the company of my friends. 0.63

23. I often feel irritated without any particular reason. 0.63

24. Muscular tension releases me with difficulty even at rest, before sleep. 0.61

25. What I already have is always insufficient for me. 0.60

26. I have this trait that things are often “not right” for me: the potatoes are too hot, and the oranges are too sour. 0.40

27. When pouring out something by eye, I more often accidentally put in too much than too little. 0.38

28. I often take on too many tasks simultaneously. 0.38

29. I am inclined to become excessively fixated on certain ideas. 0.36

30. At times those close to me grumble that I “exploit” them, make them work for me, and in doing so take too little account of their interests. 0.22

31. As a child I often whined that my parents did not love me enough and that this was precisely why they would not give in to me. 0.18

32. I sleep too much. -0.08

33. Generally speaking, in life I am the kind of person who “doesn’t give a damn.” -0.88

34. I follow the rule that the future will be whatever it will be; it concerns me little. -0.85

35. I think little about what will happen tomorrow. -0.84

36. I go with the flow of life, live by its pleasant surprises, without planning ahead. -0.84

37. It is true that I do not make plans ahead - that is simply my style of life. -0.83

38. It is difficult for me to understand people who are constantly nervous and try to foresee absolutely everything - unlike them, I am more of a person who “doesn’t give a damn.” -0.82

39. I live by going with the flow and solve problems only when they appear. -0.82

40. I am often in a state of calm serenity, like a cat licking its fur. -0.81

41. I am lazy in a good way: I will never do anything that can in principle be dispensed with. -0.81

42. I often have a pleasant feeling that there are no problems and all tasks can wait until tomorrow. -0.81

43. I have not planned anything for quite a while - somehow there is no pleasure in it. -0.81

44. I usually have a relaxed posture. -0.80

45. In life I am a person who “doesn’t give a damn” and am not inclined to exaggerate anything, especially possible troubles. -0.80

46. I am usually too lazy to think about tomorrow. -0.80

47. I easily avoid unnecessary irritation and worry over trifles. -0.79

48. My usual state is emotional relaxation (absence of any emotional tension whatsoever), accompanied by confidence that everything will be fine. -0.78

49. I am indifferent to fashion and often wear whatever comes to hand. -0.77

50. In my personal affairs I plan little in advance and more often leave myself to chance. -0.76

51. I usually do not care about most events around me. -0.75

52. If people in a group make fun of me, I scarcely notice it and usually simply pay no attention. -0.74

53. I am usually focused on the pleasures of the present moment and generally do not worry about what will happen next. -0.73

54. I am quite content to live for today without thinking about the future. -0.72

55. On average, my mood contains much more of a feeling of calm, confident comfort than anger or anxiety. -0.72

56. The work of a railway locomotive driver would suit and appeal to me more than the work of a civil-law attorney. -0.69

57. It is true that I always calmly and without offense accept both mockery of my intelligence and accusations that my views on life are childish. -0.69

58. I am quite satisfied with all my talents and abilities. -0.69

59. I am indifferent to what those around me think about me and my behavior. -0.66

60. I part with losses fairly easily, without grief or offense. -0.66

61. I am extremely little concerned by people’s opinions, - in striving toward discovery I satisfy only my own cognitive curiosity. -0.57

62. Plans that are too grandiose, lists of upcoming tasks that are too large and long, repel me and plunge me into boredom and absent-mindedness. -0.54

63. My mood is usually stable and changes little under the influence of either rewards or troubles. -0.53

64. I am indifferent to remarks and criticism directed at me - they rarely affect me seriously, and in any case do not excite me and stimulate me little. -0.52

65. I am rather indifferent to questions of my work and profession - somehow all this interests me little. -0.48

66. My self-esteem fluctuates very little and is practically independent of my current level of being in demand or of the level of external approval. -0.46

67. Sometimes I become too “stuck” on today’s pleasant chores, completely missing preparation for tomorrow. -0.30

68. Better to undersalt than oversalt; better to underdo than overdo. -0.29

INTOLERANT OF ORDINARINESS, emphasizes one’s uniqueness and “specialness,” with a tendency toward narcissism.

1. I despise ordinary people. 0.89

2. I will be very upset if I am considered as simple and ordinary as everyone else. 0.89

3. Self-admiration is among my character traits. 0.88

4. I often behave provocatively. 0.85

5. Many times I have happened to dream of the highest positions in society: the post of president, or leader of a major party, or captain of an entire branch of industry, or supreme church hierarch, or a world-famous film star, or Nobel Prize laureate, and 0.81

6. It is possible that I really am slightly “obsessed” with my superiority or my uniqueness in some respect. 0.80

7. I often appear in public as a “newsmaker,” a source of new information. 0.80

8. Proud narcissism is one of my properties. 0.79

9. Those close to me often accuse me of selfishness (whether fairly or not - does not matter). 0.75

10. By character I am calm and good-natured, respect traditions, and bring stability with me. -0.96

11. The country must sharply raise the authority of the ordinary working person, directly working in the field, on a construction site, or at a machine. -0.82

12. My more preferred genre in theater or books: 1) Heroic drama - when a solitary hero opposes the majority and does not give up. 5) Instructive and educational comedy - when an imperfect hero is re-educated by the positive environment around him. At the end - a happy ending, in which the hero is re-educated and successfully passes the final test, and society joyfully accepts him into its ranks. -0.78

13. Considers oneself an ordinary person - with the same rights as others. -0.78

14. I agree with everything in the world and accept all rules. -0.78

15. I am very obedient and always treat the instructions of superiors with great respect. -0.78

16. The opinion of the majority of the people is always the most correct opinion. -0.78

17. I would prefer to have loyal friends rather than interesting ones. -0.77

18. In a collective I like the role of formatter, finisher, the person who completes and refines the work and makes it convenient for the user. -0.76

19. I am like everyone else and want to be like everyone else - neither smarter nor more foolish, neither worse nor better. -0.76

20. I am almost always confident that my superiors are right. -0.74

21. I like being like everyone else. -0.74

22. I see only good in absolutely every young man or woman spending a year of their life working as an ordinary laborer at a factory or construction site. -0.72

23. I watch television on average more than an hour a day. -0.71

24. I am normal and “statistically average” in the overwhelming majority of my manifestations. -0.57

Need for high social status