THE ROLE OF HISTAMINE IN SOCIONIC TYPE FORMATION

(V. L. Talanov)

Histamine (Histamine) is one of the body’s most important hormones and mediators. Its receptors are present on all cells, both neural and somatic. It has long been known that an excessive increase in histamine in the body, so-called histaminosis, is accompanied by itching, urticaria, edema (or increased predisposition to them); disturbances in the respiratory system: sneezing, nasal congestion, runny nose, lacrimation, discharge of viscous sputum, bronchial spasm accompanied by coughing and suffocation; spasms in the gastrointestinal tract with stool disturbances and abdominal pain, increased gastric acidity; food intolerance, pseudoallergies to various foods or to the same food under different storage and processing conditions; the occurrence of headaches, migraine and dizziness, fluctuations in blood pressure, and increased heart rate.

All these (and other) effects of histamine are mediated through four types of its receptors on the body’s cells:

H1 receptors

Main locations: smooth muscle, endothelium, central nervous system (postsynaptic receptors)

Effects: vasodilation (dilation of capillaries), bronchoconstriction (narrowing of the bronchi), spasm of bronchial smooth muscle, separation of endothelial cells (and, as a consequence, transudation of fluid into the perivascular space, edema and urticaria), stimulation of hormone secretion by the pituitary gland, switching from sleep mode to wakefulness mode, suppression of feeding behavior, regulation of the wakefulness level of histaminergic neurons, locomotion, thermoregulation, emotions in general (and aggression and anxiety in particular), participation in memory and learning processes (suppression of recall and (re-)consolidation), development of tachycardia, reduction in atrioventricular node conduction. Humoral immunity is suppressed, while cellular immunity increases. Also, through histamine H1 receptors on cells, additional release of histamine and other inflammatory mediators occurs; expression of cell adhesion molecules on immune cells and chemotaxis of eosinophils and neutrophils increase; the antigen-presenting capacity of cells and costimulatory activity toward B cells increase; humoral immunity and IgE production are blocked; cellular immunity (Th1) is induced; IFNg secretion is induced. Stimulation of H (Histamine)1 – contracts the smooth muscles of the bronchi, intestines, and vessels of the pulmonary circulation, increases vascular permeability and secretion by the nasopharyngeal mucosa, and enhances the release of hormone-like substances involved in the regulation of arterial pressure. The main effects of H1-receptor stimulation are bronchospasm, increased vascular permeability to plasma, and skin itching.

H2 receptors

Main locations: parietal cells (in the stomach), cardiomyocytes, smooth-muscle cells[5], epithelial cells, endothelial cells, mammary gland cells, myeloid cells and lymphoid cells, dendritic cells, CNS cells.

Effects: stimulation of gastric juice secretion (more specifically, hydrochloric acid in it), increased vascular permeability, hypotension, tachycardia, bronchodilation, production of mucus in the airways. Humoral immunity increases, while cellular immunity is suppressed. Also - regulation of ion balance, reduction of eosinophil and neutrophil chemotaxis; induction of interleukin-10 synthesis, suppression of interleukin-12 synthesis by dendritic cells; development of the Th2 response and immune tolerance; induction of humoral immunity; suppression of cellular immunity; suppression of Th2 cells (that is, suppression of the function of T lymphocytes - cells that recognize antigen); an indirect role in allergy, autoimmunity, malignant diseases, and transplant rejection.

H3 receptors

They have been studied little. These are presynaptic receptors in the central and peripheral nervous systems. Their stimulation leads to suppression of the release of neuronal neurotransmitters (dopamine, GABA, acetylcholine, serotonin, norepinephrine, histamine) into the synaptic cleft; their stimulation also leads to suppression of histamine synthesis.

H4 receptors

They have been studied little. In many respects they are similar to H1 and are located predominantly in the bone marrow, blood cells, and many internal organs. Their stimulation, in particular, affects the differentiation of myeloblasts and promyelocytes; increases eosinophil chemotaxis; and serves as a signal for eosinophil degranulation.

Thus, the main known physiological and mental effects of histamine are associated with its action on H1 and H2 receptor types, which we will consider in this article.

Histamine – main genetic factors that may underlie differences in the magnitude of its activity in the body

1. Genes encoding the activity of histidine decarboxylase – the enzyme that catalyzes the conversion in the body of the amino acid histidine (obtained from food) into histamine as the final product.

2. Genes encoding the activity of diamine oxidase (DAO) – the enzyme that catalyzes the breakdown of free histamine in the body into biologically inactive metabolites. The role of related processes is also important – for example, genes affecting the release of the stress hormone cortisol, which in turn blocks the synthesis of diamine oxidase.

3. Genes regulating the processes by which histamine is released in the body from its “depot” - including from so-called mast cells. The fact is that the overwhelming majority of histamine is hidden inside the body within a number of its specialized cells, where it does not manifest its biological activity. The process by which histamine is released from cells into the blood or pericellular space in a free state, where alone it manifests its biological effect, is called “liberation” (release). Liberation can be caused, for example, by stress and by a number of chemical substances – including nicotinamide, morphine, dextran, and other exogenous or endogenous chemical agents. The processes of histamine liberation from cells into the blood also, naturally, depend on the individual’s genetics.

4. Genes encoding the number and sensitivity of the four kinds of histamine receptors (H1, H2, H3, H4, - with separate genes for each). Histamine receptors are present on all cells of the body, including neurons of the brain.

5. Genes encoding the histamine neurons’ own transmitter chain in the brain. There are few of these neurons in the brain, and all of them are located in the hypothalamus. But their axons are very long and penetrate most other regions of the brain. This specifically histaminergic neuronal network is associated, among other things, with fine regulation of sleep and wakefulness processes. Increased activity of this network is accompanied by a CNS-activating, wake-promoting effect.

6. Histamine’s interaction with other hormones and neurotransmitters is mediated through histamine receptors. H3 histamine receptors on neuronal cell bodies can directly regulate (both increasing and decreasing) the transmission of other neurotransmitters in the corresponding neuronal circuits. These include serotonin, GABA, acetylcholine, dopamine, and norepinephrine. The corresponding modulatory processes are still poorly studied. In addition, by acting through its H1 or H2 receptors on endocrine-gland cells and thereby on their activity, histamine modulates the release by these glands of their own specific neurohormones.

Thus, by acting through its H1 receptors on the adrenal medulla, histamine causes it to release adrenaline – which leads to tachycardia and many other secondary effects of histamine. Under the influence of adrenaline, arteriolar spasms and tachycardia occur, arterial pressure rises, and the smooth muscles of organs, bronchi, and bronchioles undergo spasm (histamine itself also directly contracts and spasms the smooth muscles of organs and large vessels, acting on them through its H1 receptors).

Histamine’s action on the stomach wall (on its parietal cells) and on the salivary glands through H2-type receptors increases the body’s secretion of digestive fluids – hydrochloric acid in the stomach and saliva in the mouth.

Histamine’s action on the pituitary gland (probably through H1 receptors) leads to stimulation of secretion of pituitary and neurohypophyseal hormones – in particular, to increased production of corticotropin in the anterior pituitary and to release from neurohypophyseal axons into the blood of vasopressin (ADH, antidiuretic hormone, which delays the excretion of water by the kidneys and affects the CNS). At the same time, the effects of vasopressin and histamine itself on diuresis are opposite with respect to inhibition of urination – histamine, through its H2 receptors, directly stimulates and accelerates urinary excretion by the kidneys – that is, it increases diuresis. The effects of histamine and the vasopressin “awakened” by it on the cardiovascular system are also oppositely directed – whereas histamine through H2 and partly H1 receptors lowers blood pressure (up to hypotensive fainting), vasopressin, conversely, raises it. Thus, some direct effects of histamine may be masked by other neurohormones secondarily released into the blood by it – depending on the intensity of their release, which is encoded by entirely different genes having no direct relation to histamine itself.

High concentrations of free histamine reduce serotonin production – that is, these neurohormones are partly in reciprocal relations in the body.

Effects of Histamine on the body – THROUGH STIMULATION OF ITS H1 RECEPTORS ON CELLS

1. Causes dilation of capillaries and blood stasis in them, which leads to increased permeability of their walls, escape of plasma from the vessels, edema of surrounding tissues, and blood thickening. Intensifies any inflammation, which to a considerable extent causes subsequent pain through direct action on nerve endings. Frequent itching, dermatitis, urticaria, edema, increased exudates.

2. By causing dilation of small vessels (their vasodilation), leads to a reduction in arterial pressure. In addition, histamine is itself a powerful vasoactive substance because it affects the release of the active vasodilator nitric oxide, which also lowers blood pressure. Histamine’s direct action on large vessels through H1 receptors is constricting, spasmodic (vasoconstrictive). Because of this ambiguous action on blood pressure, under the influence of histamine arterial pressure may first jump upward, then be replaced by a fall. More often, chronic elevation of histamine release leads to reduced pressure (hypotension), up to hypotensive fainting (which occurs more often in people predisposed to high histamine during stress and agitation, which directly provoke release of histamine into the blood from body cells containing it).

3. Headache (continuous or severe - a consequence of vascular disturbances caused by histamine).

4. Nervousness (a combination of increased aggression and increased anxiety).

5. Slight acceleration and disinhibition of motor reactions.

6. Tachycardia – acceleration of heart rate (partly - an effect of histamine-induced release of adrenaline from the adrenal cortex through H1 receptors).

7. Flushing or reddening of the face (an effect of capillary dilation and increased permeability under the direct action of histamine on their H1 and H2 receptors).

8. Difficulty breathing, bronchospasm (contraction of bronchial smooth muscle, action on H1 receptors).

9. At high doses, diarrhea, severe nausea and vomiting, and abdominal spasms with acute pain in the intestinal region are possible (a consequence of contraction of intestinal smooth muscle, action on H1 receptors).

10. Mental effects – in addition to nervousness, increased anxiety, and acceleration of motor reactions, deterioration of memory is also observed (impairment of its consolidation and reconsolidation processes).

11. Suppression of feeding behavior, reduced appetite.

12. Blocking of humoral immunity and IgE production; but induction (enhancement) of cellular immunity (Th1).

Effects of Histamine on the body – THROUGH STIMULATION OF ITS H2 RECEPTORS ON CELLS

1. Hypotension (dizziness or fainting, including orthostatic fainting – when rising rapidly from a sitting or lying position).

2. Relaxation of bronchial musculature, dilation of the bronchi.

3. Increased secretion by gastric and salivary glands, gastrointestinal disturbances resembling symptoms of peptic ulcer disease as a consequence of increased secretion of hydrochloric acid in the stomach, metallic taste in the mouth. Because of increased acidity – provocation and aggravation of acid gastritis and ulcers of the stomach and duodenum.

4. Production of mucus in the airways (sputum in the bronchi, nasal mucus, increased secretion of liquid nasal mucus as a reflex response to dust, cooling of the feet, etc., a tendency toward prolonged attacks of uncontrollable sneezing with simultaneous discharge of mucus from the nose, runny noses “with mucus” in response to any viral inflammation of the nasal mucosa).

5. Induction of humoral immunity; but suppression of cellular immunity (for this reason – increased susceptibility to viral acute respiratory disease (ARD)); suppression of Th2 cells.

6. An indirect role in aggravating the symptomatology of allergies and autoimmune diseases, as well as in implant rejection.

7. Stimulation of urinary excretion by the kidneys (direct action through H2-type receptors).

Effects of Histamine on the body – UNDIFFERENTIATED ROLE OF DIFFERENT TYPES OF HISTAMINE RECEPTORS

1. Tremor (especially tremor of the hands and fingers).

2. Muscle weakness and myalgia (muscle soreness).

3. Miscellaneous – intolerance to a number of foods (food pseudoallergies), motion sickness, nausea.

4. Reduction of serotonin effects due to decreased serotonin production under the influence of histamine.

On the basis of the above signs of the physiological and psychological actions of histamine known from the scientific literature, we formed the following clusters from questionnaire items, fully or partially serving as markers of the specific effects of histamine:

WITH PREDOMINANT ACTION ON H1 RECEPTORS

1. H1 receptors - their activation by histamine (itching, dermatitis, urticaria, edema)
2. H1 receptors - their activation by histamine (capillary dilation, facial skin hyperemia, sensation of “flushes”, pink dermographism of the skin)
3. H1 receptors - their activation by histamine (headaches of vascular origin)
4. H1 receptors - their activation by histamine (contraction-spasms of bronchial smooth muscle with difficulty breathing)
5. H1 receptors - their activation by histamine (weakening of memory consolidation processes)
6. H1 receptors - their activation by histamine (wake-promoting action, anxious-aggressive “nervousness”)
7. H1 receptors - their activation by histamine (restriction of drive toward food)

WITH PREDOMINANT ACTION ON H2 RECEPTORS

8. H1+H2 receptors - their activation by histamine (hypotension, orthostatic collapses – reduced arterial pressure, dizziness on standing)
9. H1+H2 receptors - their activation by histamine (increased mucus production in the airways)
10. H1+H2 receptors - their activation by histamine - excitation of the adrenal system with acceleration of the pulse (tachycardia)
11. H2 receptors - their activation by histamine (weakening of cellular immunity, increased susceptibility to ARD)
12. H2 receptors - their activation by histamine (stimulation of the digestive glands, gastric and salivary, increased acidity of gastric juice)
13. H2 receptors - their activation by histamine (direct stimulation by histamine of urinary excretion by the kidneys)
14. H2 receptors - their activation by histamine (relaxation of bronchial smooth muscle, dilation of the bronchi)
15. H2 receptors - their activation by histamine (indirect aggravation of the symptomatology of allergies and autoimmune diseases)

MISCELLANEOUS

16. Tremor of the hands and fingers
17. Muscle weakness, myalgia
18. Various gastrointestinal disorders. Intolerance to a number of foods (food pseudoallergies characteristic of histaminosis), motion sickness, nausea, diarrhea, elements of “irritable bowel” symptomatology.

We shall describe the composition of these 19 clusters in greater detail (after each item – the linear correlation of its socionic type profile with the averaged type profile of the entire cluster):

1) H1 receptors - their activation by histamine (itching, dermatitis, urticaria, edema)

1. Sometimes a substantial part of my body itches. 0.90
2. At least once a year or more often, I have (or experience exacerbations of) itchy dermatitis. 0.88
3. An insect bite almost always produces a large inflamed “bump” on my skin. 0.88
4. I have experienced so-called urticaria, with prolonged itching (for several days) and reddening of the skin. 0.81
5. Nettle burns quickly produce intensely itching blisters on my skin. 0.71
6. Over the past three years, I have clearly had abscesses (internal inflammations) in the muscles of the buttock more than once. 0.71
7. Mosquito bites always produce intensely itching blisters on my skin. 0.70
8. The slightest thing - some wound, scratch, insect bite, or allergen - and I develop severe inflammation or edema. 0.70
9. From splinters, and sometimes even from scratches, small pustules quite often “appear” at that site on my body. 0.67
10. When I see someone scratching, I often automatically feel the urge to scratch myself as well. 0.67
11. My skin has an increased predisposition to all kinds of infections (for example, pimples often arise at the sites of blackheads, scratches usually become inflamed, there may also be increased susceptibility to fungal diseases, etc.). 0.67
12. Even around small bruises and scratches I usually develop noticeable painful swelling. 0.64
13. Almost any bruise I get necessarily ends in a colored bruise. 0.64
14. I sometimes have severe swelling of the face, when even my eyes become slightly “swollen shut” under the eyelids and turn into slits. 0.59
15. I often develop severely inflamed pimples at the sites of blackheads in the skin. 0.55
16. At least over the last several days I have often experienced uncomfortable sensations in the body - something itches, or I cannot lie still comfortably, or something somewhere in the body simply feels “not right”. 0.49
17. I have a habit of scratching my head behind my ears rather often (in any case, several times a day). 0.46

No. 1. H1 receptors - their activation by histamine (itching, dermatitis, urticaria, edema)

(averaging the profiles of 18 scale questions, 25773 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

2) H1 receptors - their activation by histamine (capillary dilation, facial skin hyperemia, sensation of “flushes”, pink dermographism of the skin)

1. People say that my face sometimes reddens, revealing my excited state. 0.84
2. Quite regularly (at least a couple of times a month), I experience “flushes” as if heat were coming to the skin of my face (if I look in a mirror, my face becomes pink at such times). 0.77
3. I blush easily from excitement or embarrassment. 0.71
4. Sometimes blood rushes to my face and my face becomes pink. 0.68
5. Sometimes my face reddens from a rush of blood to the skin. 0.65
6. When irritated, my face sometimes reddens. 0.64
7. When I am angry, the skin on my face generally fills with blood and reddens. 0.63
8. I quite often have a subjective sensation of heat in my head and face (or a sensation of sudden “flushes” of heat), outside infectious illnesses (I notice this in myself at least once every two weeks). 0.45
9. When I am nervous, red patches sometimes appear on my face. 0.38
10. Because of shyness in communication, my face is sometimes covered with red patches. 0.25
11. If the skin of my arm is lightly scratched with something, a pink line immediately appears at the site of the scratch (but not a white line). - check. -0.22

12. It is true that from excitement my face never reddens or becomes hot; blood practically never rushes to my cheeks and face. -0.85
13. From anger, the skin on my face becomes cold. -0.75
14. It is true that I never have such flushes of blood to the face that the skin becomes hot and pink from excitement. -0.71
15. My facial skin is generally pale; it never reddens even when I am excited. -0.39
16. It is true that I never have a blush on my cheeks at ordinary air temperature. -0.21
17. If the skin of my arm is scratched with something, a white line appears at that site for several seconds (but not a pink or red line). - check. 0.05
18. In some situations I often turn pale, as if blood were draining from my face. 0.03

No. 2. H1 receptors - their activation by histamine (capillary dilation, facial skin hyperemia, sensation of “flushes”, pink dermographism of the skin)

(averaging the profiles of 18 scale questions, 13681 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

3) H1 receptors - their activation by histamine (headaches of vascular origin)

1. I get headaches quite often - on average, at least once a month. 0.88
2. I often have headaches or pain in the back. 0.85
3. Sometimes, when it is quiet around me, I hear ringing/noise in my ears. 0.83
4. I get headaches more often than once a month. 0.82
5. I have headaches in my right temple associated with hunger - they occur if I skip lunch or forget to have dinner. 0.64
6. I have spasmodic headaches (migraines). 0.51
7. I have a throbbing headache on one side of the head, radiating to the back of the head, usually occurring in connection with bad weather - increased air temperature and humidity, increased cloudiness, etc. 0.45
8. More than once a month I have migraine - a very intense throbbing headache of a sharply stabbing character (specifically throbbing or sharply stabbing, rather than evenly and continuously compressive), localized more on one side of the head. 0.38

No. 3. H1 receptors - their activation by histamine (headaches of vascular origin)

(averaging the profiles of 8 scale questions, 10270 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

4) H1 receptors - their activation by histamine (contraction-spasms of bronchial smooth muscle with difficulty breathing)

1. I often have a sensation of difficult breathing (I notice this in myself at least once every two weeks). 0.82
2. I sometimes have a feeling of heaviness in my chest, with the sensation that breathing is difficult, at least not entirely easy - that is, without the usual ease and imperceptibility of breathing to myself. 0.69
3. I sometimes find it difficult to breathe. 0.64
4. Sometimes I become afraid that I am about to suffocate. 0.62
5. I have bronchial spasms when breathing becomes very difficult - I breathe rapidly and almost “with wheezing”, yet still do not get enough air. 0.61
6. My breathing is often somehow constricted, as if the air has somehow become different and there is not enough of it with each breath (at such times I sometimes feel a kind of tightness in the lower part of my neck and in my chest). 0.57
7. I have had asthma attacks with a feeling of suffocation. 0.33
8. I have had bronchial asthma or severe allergies to something. 0.27
9. I have had attacks of bronchial asthma when breathing was constricted and there was not enough air. 0.02

10. My breathing is always easy, unhurried, and free - I simply do not pay attention to it. -0.73
11. It is true that I have never had breathing difficulties (in the form of asthma or respiratory spasm), at least apart from taking any medications that affect breathing. -0.53

No. 4. H1 receptors - their activation by histamine (contraction-spasms of bronchial smooth muscle with difficulty breathing)

(averaging the profiles of 14 scale questions, 15784 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

5) H1 receptors - their activation by histamine (weakening of memory consolidation and recall processes)

1. I have memory problems. 0.91
2. Quite often (at least once every couple of days), I go to do something, but along the way I become distracted by something extraneous for literally a minute, and immediately afterward I completely forget what I had been going to do. 0.90
3. I have problems with the capacity of attention - I often fail to notice something important. 0.90
4. If I become distracted for a minute, I easily forget what I had been talking about before that. 0.90
5. I sometimes get confused about the order of events. 0.89
6. My speech is not particularly clear and consistent; in conversation I sometimes jump from one thought to another and lose the main line of the narrative. 0.89
7. I am usually easily distracted; it is difficult for me to concentrate attention for a long time and focus on one thing. 0.88
8. Sometimes I put a needed object somewhere, then become distracted by something for literally a minute, and immediately afterward I absolutely cannot remember where I put it. 0.86
9. There are moments when I automatically perform some complex actions and then cannot account to myself for exactly what I did (that is, everything is quickly forgotten). 0.85
10. Sometimes by the end of a long sentence I forget its beginning; I do not even remember from its meaning what was being discussed there. 0.85
11. I easily and often forget ideas that came to mind for a time, until the next occasion brings them up. 0.83
12. Sometimes I completely forget the names of certain objects for several seconds. 0.83
13. Sometimes I cannot remember events of the recent preceding hours. 0.82
14. I easily forget what I was saying if I am interrupted by an unrelated question. 0.81
15. Sometimes I forget the names of certain objects - effort is required to remember them. 0.80
16. I often struggle to catch some elusive association or analogy and cannot manage to do so. 0.80
17. I have problems concentrating attention and with “gathering my thoughts together”. 0.80
18. Sometimes I look at an object and cannot remember its name. 0.79
19. I have memory problems. 0.79
20. While solving some task, I keep forgetting its conditions and have to look back at the initial text again and again. 0.78
21. I easily forget a previous desire or agree to a substitute if I cannot satisfy some need immediately. 0.77
22. I almost never managed to absorb instructional lecture material directly during lectures - at some point I would invariably “drop out” of the explanation, and afterward I always had to learn the material again by reading the textbook and notes with my own eyes. 0.77
23. I often struggle to find the “right” word - it seems to be somewhere in my mind, but I cannot recall the name. 0.74
24. I often forget where I put things in my home. 0.74
25. It is difficult for me to retain a visual situation and its changes in working memory for long; everything just registered visually quickly seems to “fall away” somewhere - I certainly could not work as an air-traffic controller. 0.63
26. I notice memory problems in myself - I often forget what I would like to remember. 0.59

27. When putting forward arguments in a dispute, I always know in advance what I want to lead the conversation toward. -0.89
28. It is easy for me to keep my attention on the course of my reasoning. -0.88
29. I remain faithful for many months or years to a goal once set and calculated, and nothing can divert me from the intended course. -0.86
30. I memorize numbers, formulas, factual information, and peculiarities of pronunciation in different people well and quickly by ear. -0.83
31. I remember perfectly even the smallest things I have done over the last ten minutes; I do not have lapses in memory. -0.82
32. I have an excellently developed mental ability not to lose the point at which I stopped while carrying out a task if I had to switch my attention temporarily to something else. -0.82
33. I easily and accurately remember people’s first and last names, even long and complicated ones. -0.78
34. Most of the time I have a good memory that firmly keeps in mind all my plans and everything important in general. -0.77
35. Within about fifteen seconds I can quite well remember what was notable about and how my affairs and concerns differed from today’s on exactly the same day of the week exactly 7 days ago. -0.77

No. 5. H1 receptors - their activation by histamine (weakening of memory consolidation and reconsolidation processes)

(averaging the profiles of 35 scale questions, 74330 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

6) H1 receptors - their activation by histamine (wake-promoting action, anxious-aggressive “nervousness”)

1. Memories easily arise in me, sometimes for the slightest reasons, or anxious thoughts “flare up”. 0.97
2. I often get nervous over absolute trifles. 0.94
3. Suspiciousness is part of my character: sometimes I imagine something unpleasant or dangerous that does not actually exist. 0.92
4. I often feel nervous before I have even started doing anything. 0.90
5. It is difficult for me to fall asleep again if I wake up. 0.37

6. I am stress-resistant; I can endure severe nervous strain for a long time without problems, without particular fatigue and without any ailments. -0.90
7. I categorically do not remember ever feeling nauseated in the morning “from nerves”. -0.86
8. I am a very deep sleeper - a cannon would not wake me. -0.74
9. I sleep well and calmly, without insomnia or waking in the middle of the night. -0.73
10. In the middle of the day I sometimes fall asleep without wanting to (although I also slept at night). 0.16

No. 6. H1 receptors - their activation by histamine (wake-promoting action, anxious-aggressive “nervousness”)

(averaging the profiles of 10 scale questions, 14394 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

7) H1 receptors - their activation by histamine (restriction of drive toward food)

1. I have a poor appetite; I eat more often “out of obligation”. 0.96
2. Food rarely stimulates my appetite; often it generally seems almost tasteless. 0.93
3. I usually eat very little or simply out of obligation - I am rarely drawn to food. 0.92
4. I am rarely drawn to food; a feeling of hunger is not characteristic of me. 0.91
5. I rarely feel hunger, even if I have not eaten all day. 0.91
6. Food generally does not give me much appetite even while I am eating - food usually leaves me indifferent. I do not feel the “sweetness of anticipation” when beginning to eat it. 0.89

7. I have a good appetite; food always seems tasty to me. -0.90
8. I know how to cook food for myself and enjoy doing so. -0.88
9. I have an excessively increased appetite, and because of this I am overweight. -0.46

No. 7. H1 receptors - their activation by histamine (restriction of drive toward food)

(averaging the profiles of 9 scale questions, 15888 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

8) H1+H2 receptors - their activation by histamine (hypotension, orthostatic collapses – reduced arterial pressure, dizziness on standing)

1. I have low blood pressure. 0.83
2. At least a couple of times a month, my vision darkens and I become dizzy when I quickly rise from bed and stand up. 0.82
3. It has happened that, after abruptly standing up from a lying position, a second later I felt that everything before my eyes was floating and my legs would not support me, and this lasted for several seconds. 0.79
4. Compared with other people, I generally have reduced arterial pressure (hypotension). 0.76
5. I have low blood pressure. 0.59
6. I have attacks of dizziness, especially when I rise abruptly from a sitting position - just after standing up, I suddenly feel that my head begins to spin and that I am somehow being “pulled” to one side (this happens at least once a month). 0.51
7. When I stand up from a sitting position, I quite often become dizzy. 0.46
8. My systolic arterial pressure quite often turns out to be below 100 mm Hg. 0.45

9. My blood pressure often rises. -0.44
10. My arterial pressure is usually elevated or somewhat above normal. -0.39

No. 8. H1+H2 receptors - their activation by histamine (hypotension, orthostatic collapses – reduced arterial pressure, dizziness on standing)

(averaging the profiles of 10 scale questions, 5432 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

9) H1+H2 receptors - their activation by histamine (increased mucus production in the airways)

1. My nose reflexively starts producing mucus and I begin sneezing uncontrollably if I walk barefoot on a cold floor. 0.79
2. My nose is often congested and I cannot breathe well through it, even when I do not have a cold. 0.76
3. At least once a week, I have an attack of intense and uncontrollable sneezing - for several minutes in succession. 0.50

No. 9. H1+H2 receptors - their activation by histamine (increased mucus production in the airways)

(averaging the profiles of 3 scale questions, 3863 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

10) H1+H2 receptors - their activation by histamine - excitation of the adrenal system with acceleration of the pulse (tachycardia)

1. My heart rate is usually accelerated (my heart almost always beats faster than 70 beats per minute). 0.90
2. I often have episodes of rapid heartbeat. 0.84
3. My pulse and breathing often become noticeably faster. 0.81
4. I only need to walk up a couple of flights of stairs for my pulse to jump above one hundred beats per minute. 0.73
5. I often become excited for one reason or another - with an accelerated heart rate, and sometimes also a sensation of a “rush of blood” (that is, a temporary increase in arterial pressure). 0.71
6. I often have states in which I am excited and at the same time my palms are moist, my pulse is accelerated, and my breathing becomes intermittent. 0.63
7. When nervous, I often feel my heartbeat accelerate. 0.50
8. I usually have a fast pulse (fast heart rhythm). 0.29

9. My heart always beats slowly and unhurriedly, no more than 60-70 beats per minute, and does not tend to accelerate from excitement. -0.74
10. My pulse is usually slow, fewer than 65 beats per minute. -0.67

No. 10. H1+H2 receptors - their activation by histamine - excitation of the adrenal system with acceleration of the pulse (tachycardia)

(averaging the profiles of 10 scale questions, 12185 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

11) H2 receptors - their activation by histamine (weakening of cellular immunity, increased susceptibility to ARD)

1. I often catch colds - my immunity against cold viruses is clearly reduced (meaning various ARDs with a runny nose or “itching” in the nose and throat). 0.94
2. During the autumn-spring period, when there are many sick people in the streets, I very easily “catch” a cold or influenza. 0.90
3. Various viral respiratory diseases with itching in the nasopharynx and a runny nose “attach themselves” to me easily and run a rather severe course. 0.83
4. I often catch colds and easily develop runny noses. 0.81

5. Compared with many of my friends, I suffer from various cold-related “runny noses” extremely rarely. -0.93

No. 11. H2 receptors - their activation by histamine (weakening of cellular immunity, increased susceptibility to ARD)

(averaging the profiles of 5 scale questions, 4927 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

12) H2 receptors - their activation by histamine (stimulation of the digestive glands, gastric and salivary, increased acidity of gastric juice)

1. If someone next to me eats a lemon, I automatically feel saliva being secreted and as though I can taste the lemon in my own mouth. 0.86
2. When someone nearby starts eating something, I often immediately want to eat the same thing, so that “my mouth waters”. 0.85
3. I often notice that if someone nearby begins drinking greedily and with appetite, I myself immediately start wanting to drink after that person. 0.81
4. The smell of food always excites me and stimulates my appetite; smells of food being prepared usually immediately “make my mouth water”. 0.67
5. When I think of a lemon, I immediately feel saliva being secreted in my mouth. 0.60
6. I am often troubled by heaviness in the stomach region. 0.57
7. Because of increased stomach acidity, at least once a month I have to take baking soda or antacids to eliminate heartburn and other unpleasant sensations in my abdomen. 0.52
8. The smell of food always excites and stimulates me; smells of food being prepared usually “make my mouth water”. 0.41
9. My stomach does not tolerate large quantities of meat well. 0.30

10. I have been found to have reduced acidity of gastric juice. 0.10
11. At least once a month I have heartburn with belching that resembles the smell of a rotten egg. 0.04

No. 12. H2 receptors - their activation by histamine (stimulation of the digestive glands, gastric and salivary, increased acidity of gastric juice)

(averaging the profiles of 11 scale questions, 15054 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

13) H2 receptors - their activation by histamine (direct stimulation by histamine of urinary excretion by the kidneys)

1. After beer or watermelon I always quickly feel the urge to go to the toilet (within an hour, no later). 0.91

2. It happens that during the day I feel no need to go to the toilet “to urinate” for 6-8 hours in succession. -0.77
3. It is true that I usually urinate infrequently, on average no more than a couple of times a day. -0.76

No. 13. H2 receptors - their activation by histamine (direct stimulation by histamine of urinary excretion by the kidneys)

(averaging the profiles of 3 scale questions, 1391 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

14) H2 receptors - their activation by histamine (relaxation of bronchial smooth muscle, dilation of the bronchial lumen). In addition to histamine’s action on H2 receptors, which widens the bronchial lumen (whereas its action on H1 receptors narrows it), an optimum level of acetylcholine activity also plays a significant role in “free breathing” (low values lead to weakness of the respiratory center, to infrequent, shallow, and arrhythmic breathing, while excessively high values lead to its paralysis, that is, to respiratory arrest)

1. My breathing is always easy, unhurried, and free - I simply do not pay attention to it. 0.73
2. It is true that I have never had breathing difficulties (in the form of asthma or respiratory spasm), at least apart from taking any medications that affect breathing. 0.53

3. I often have a sensation of difficult breathing (I notice this in myself at least once every two weeks). -0.82
4. I sometimes have a feeling of heaviness in my chest, with the sensation that breathing is difficult, at least not entirely easy - that is, without the usual ease and imperceptibility of breathing to myself. -0.69
5. I sometimes find it difficult to breathe. -0.64
6. Sometimes I become afraid that I am about to suffocate. -0.62
7. I have bronchial spasms when breathing becomes very difficult - I breathe rapidly and almost “with wheezing”, yet still do not get enough air. -0.61
8. My breathing is often somehow constricted, as if the air has somehow become different and there is not enough of it with each breath (at such times I sometimes feel a kind of tightness in the lower part of my neck and in my chest). -0.57
9. I have had asthma attacks with a feeling of suffocation. -0.33
10. I have had bronchial asthma or severe allergies to something. -0.27
11. I have had attacks of bronchial asthma when breathing was constricted and there was not enough air. -0.02

No. 14. H2 receptors - their activation by histamine (relaxation of bronchial smooth muscle, dilation of the bronchi). In addition to histamine’s action on H2 receptors, which widens the bronchial lumen (whereas its action on H1 receptors narrows it), an optimum level of acetylcholine activity also plays a significant role in “free breathing” (low values lead to weakness of the respiratory center, to infrequent, shallow, and arrhythmic breathing, while excessively high values lead to its paralysis, that is, to respiratory arrest)

(averaging the profiles of 11 scale questions, 12548 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

15) H2 receptors - their activation by histamine (indirect aggravation of the symptomatology of allergies and autoimmune diseases)

1. I have had allergic diseases (allergic rhinitis, hay fever, urticaria, eczema, etc.). 0.79
2. I have allergic reactions to something. 0.60
3. I have had urticaria or eczema more than once. 0.57
4. I am allergic to something (pollen, or fur, or oranges, or some medications, etc.). 0.50
5. I have had allergic skin eruptions. 0.48
6. I have been diagnosed with rheumatoid arthritis or some other autoimmune diseases associated with excessive enhancement of the internal immune response. 0.25
7. Some antibiotics or other medications cause an allergic reaction in me. 0.21

8. My immune system is fine. -0.74
9. It is true that I have never had any allergic reactions in my life. -0.50
10. What has happened to you in your life? 1) Allergy 5) Migraines 3) Neither one nor the other occurred, or both occurred. -0.36

No. 15. H2 receptors - their activation by histamine (indirect aggravation of the symptomatology of allergies and autoimmune diseases)

(averaging the profiles of 10 scale questions, 17881 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

16) Tremor of the hands and fingers

1. Even outside illness I sometimes experience chills, when my body begins to shake as if from cold (this happens at least once a month). 0.85
2. Sometimes rapid trembling begins in my body (even when I am not cold), and it cannot be stopped until it passes on its own. 0.84
3. I have tremor in my limbs when, for example, my hand begins to “shake” (I encounter this at least once a month). 0.82
4. Sometimes a glass or plate trembles in my hand. 0.80
5. After physical exertion (running, doing squats, carrying something on my back, etc.), my fingers often shake or tremble for several minutes afterward (although I may not have done anything directly with my hands). 0.75
6. When I am nervous, my hands often tremble. 0.49

7. It is true that my hands never tremble. -0.78
8. My hands never tremble. -0.76

No. 16. Tremor of the hands and fingers

(averaging the profiles of 8 scale questions, 8397 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

17) Muscle weakness, myalgia. This symptom may be provoked not only by histamine, but to an even greater extent – by acetylcholine deficiency (deficiency of cholinergic activity)

1. I often find it difficult to climb stairs - not because of my heart and not because of shortness of breath, but specifically because my muscles tire quickly. 0.89
2. It is true that I do not like physical work. 0.80
3. At least once a week or even more often, I experience soreness in my muscles or bones. 0.72
4. I often feel tired during the day, even if I had a good night’s sleep. 0.70
5. I pay attention to any unpleasant bodily sensations (itching, tingling, numbness, vibration, pain, heaviness, etc.) much more often than to pleasant ones. 0.60
6. I have muscle pain. 0.60
7. Sometimes (at least a couple of times a month) almost my whole body hurts, and pain is felt inside the muscles. 0.59
8. I periodically have internal muscle pain (in no way related to physical exertion or injuries), which is felt especially acutely when a muscle is pressed with a finger. 0.44

9. I can engage in physical work for quite a long time before I become tired. -0.92
10. I am capable of performing prolonged physical work without fatigue. -0.90
11. I can perform physical work for a long time without feeling or noticing fatigue at all. -0.86

No. 17. Muscle weakness, myalgia

(averaging the profiles of 11 scale questions, 12318 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

18) Various gastrointestinal disorders. Intolerance to a number of foods (food pseudoallergies characteristic of histaminosis), motion sickness, nausea, diarrhea, elements of “irritable bowel” symptomatology

1. Quite often my intestines “rumble” and I feel the urge to go to the toilet, outside cases of food poisoning (I notice this in myself at least once every two weeks). 0.78
2. I often have some kind of digestive problems (nausea, diarrhea, stomach spasms, heartburn, or constipation). 0.76
3. I often experience nausea (and occasionally vomiting) for various reasons - in the morning from nervousness, or after eating, or even with slight motion sickness. 0.74
4. There are foods that other people eat without difficulty but that I have been disgusted by eating since childhood. 0.70
5. In some form of transport I sometimes become motion-sick to the point of a strong and difficult-to-suppress feeling of nausea. 0.64
6. I often feel rumbling in the intestinal region during the day or in the morning. 0.63
7. I have food allergies (I cannot tolerate some foods). 0.21

8. I like simple and coarse, but abundant food. -0.90

No. 18. Various gastrointestinal disorders. Intolerance to a number of foods (food pseudoallergies characteristic of histaminosis), motion sickness, nausea, diarrhea, elements of “irritable bowel” symptomatology.

(averaging the profiles of 8 scale questions, 4805 respondent answers in total, all profiles, except the 2nd and 3rd type profiles, are normalized to a unit sigma of the type profile). All profiles are given after corrective factor rotation.

SUMMARY RESULTS

(In the summary-result tables below, all profiles are given in real values, that is, for the types – in fractions of the approximate standard deviation of the general population, without profile normalization.)

Unnormalized trait profile

Contribution of traits to the variance of the property, %:

Unnormalized type profile (deviations from the mean in fractions of the population standard deviation):

Unnormalized functional profile (recalculated from the trait profile)

CONCLUSIONS

1. Averaged across all histamine effects, EIE is the “champion”. This corresponds to the fact that, as we previously showed in other studies, EIE is also the socion’s “anti-champion” for serotonin (recall that histamine is in a reciprocal relationship with the concentration of free serotonin). ILE is in second place “for histamine”. In this case, ILE also has an increased probability of hyperemia, memory disturbances, hypotension with orthostatic collapses and dizziness, tachycardia, weakening of cellular immunity, tremor, and symptoms of gastrointestinal disorders. Conversely, the lowest level of histamine activity is found in SLE and LSI.

2. Among the traits, histamine is associated with increased Intuition, Carelessness, Questimity, and Dynamics. Moreover, in the case of histamine effects on its H1 receptors, the association with Intuition predominates, while Carelessness is in second place. In the case of effects associated with H2 receptors, by contrast, the association of histamine with Carelessness predominates, while Intuition is in second place.

3. Histamine clearly contributes to the Intuitive pole. However, this is far from the only mediator affecting Intuition-Sensing. Other mediators that we established earlier are acetylcholine, serotonin, and dopamine (acetylcholine and serotonin contribute to Sensing, dopamine – partly to Intuition, following its general extraverted activity).

4. Any neurohormones or neurotransmitters whose activity is genetically encoded should, according to evolutionary rules, have a greater influence on dual traits – that is, on those whose poles are statistically balanced (levelled out) in the offspring of two dual parents (since the predominance of duals among married couples has been statistically confirmed by questionnaires). If some hormone had its strongest influence on non-dual traits (such as Carelessness, Yielding, nalnost, etc.), this would contradict evolutionary rules, because in the offspring of duals it would lead to divergence of genetically encoded properties, that is, to their further separation in the offspring toward maladaptive extreme, polar-end values.

In any case, as we can see, this rule holds for histamine. Although it partly encodes non-dual Carelessness, the simultaneous contribution to the variance of three other strictly dual traits that are also influenced by histamine (Intuition, Questimity, and Dynamics) turns out to be higher than that of non-dual Carelessness.

5. When assembling marker properties that determine the semantic content of non-dual traits, this circumstance (indicated in the preceding conclusion) must be taken into account. Specifically, when studying markers of Carelessness, they should be collected not by correlations with Carelessness as such, but by correlations of questionnaire items with different paired combinations of Carelessness and dual traits (Carelessness+Extraversion, Carelessness+Introversion, Carelessness+Intuition, Carelessness+Sensing, etc.). Only in this case is there a high chance of identifying real genetically encoded properties that are PARTLY substantially associated with Carelessness (or Yielding, or Democracy, etc.). Precisely PARTLY, because there cannot be a complete one-to-one correspondence between, on the one hand, Carelessness (or any other non-dual trait), and, on the other hand, a genetically encoded property. Such one-to-one relationships (that is, without any “partly”) are theoretically possible only for dual traits. In other words, to search for the semantic content of non-dual traits, one should seek this semantic content not in general and as a whole, but only fractionally, in various small groups composed of one non-dual trait of interest to us and a second trait that is necessarily dual. In a more thorough study of the full diversity of properties of Carelessness, which we are currently conducting, this approach is already bearing positive fruit.

6. Can antagonists of histamine that penetrate the brain through the blood-brain barrier (for example, antihistamines such as Dimedrol and Suprastin) be used to temporarily shift a person’s balance toward Sensing? Unfortunately, no. At least, this is impossible when using the indicated or, in general, any other modern histamine antagonists. This is because all of them, without exception, are known, for some mysterious reason, to possess not only antihistamine but also anticholinergic action. That is, on the one hand, by reducing histamine activity they seemingly should shift the balance toward Sensing, but by simultaneously reducing acetylcholine activity they return the balance to its previous Intuition values. What they actually do in the end is merely temporarily increase drowsiness, because they suppress the action of two excitatory mediators at once (both acetylcholine and histamine). Of known medical preparations, only preparations that selectively enhance acetylcholine activity can temporarily (for half an hour to an hour) increase a person’s Sensing (for example, reversible, mildly acting inhibitors of the enzyme acetylcholinesterase). That they really do this, temporarily turning an Intuitive type into a Sensing type, is a scientific fact.

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St. Petersburg, January 2021.

Address of the first publication of the preprint: http://otkroysebya.ru/Histamine.docx