31 March 2017

Depression: myths and reality

Alexander Savostyanov, Yulia Chernaya, "Trinity Variant"

According to official statistics of the World Health Association, 350 million people in the world need medical care due to depression. And the number of people who are diagnosed with this is constantly growing… Novosibirsk scientists have received a grant from the Russian Science Foundation to study the propensity to depression and the peculiarities of the organization of oscillatory networks of the brain. The aim of the project is to study the predisposition to depression at preclinical stages and to study the individual characteristics of this pathology at clinical stages. Predisposition to depression depends on both genetic factors and personal characteristics of people and is reflected in the mechanisms of the brain.

This complex project, which involves both geneticists, physiologists, and psychologists, has already had its first results. We asked Ved. nauch to tell about them. sotr. Laboratories of Differential Psychophysiology of the Institute of Physiology and Fundamental Medicine, Head. Laboratory of biological markers of human social behavior at the Faculty of Humanities of NSU, art. scientific. sotr. Institute of Cytology and Genetics SB RAS Alexander Savostyanov.

A. Savostyanov. Photo of the NSU press service

The lady on the watch reacts very kindly to the surname "Savostyanov": they are used to the streams of women coming to the professor's office. And the point, of course, is not that Alexander is a female favorite. Just in the epicenter of his attention now is a disease that is more often fixed in women. And the further, the more often.

But Alexander begins our conversation by debunking myths: it turned out that the number of patients has not increased recently, and women do not get sick more often than men:

"Indeed, in the last twenty years, there has been an increase in the number of patients diagnosed with depression, autism, hyperactivity and a whole range of mental illnesses in the world. But indirect data tell us that the number of cases, most likely, has not changed fundamentally. However, the number of people seeking psychiatric help has changed. And here the awareness of the population and the level of diagnosis already affect. In addition, it should be borne in mind that even 15 years ago, an appeal to a psychiatrist could be perceived by people around the patient as something shameful. The patient could subsequently have problems with hiring as a result of the fact that he was undergoing psychiatric treatment. Fortunately, such problems are in the past. Nevertheless, even today we do not identify all patients. In our clinic, 70% of patients with depression are women. But if we analyze the problem comprehensively: taking into account cases of suicide, alcoholism and other behavioral consequences associated with depression, it turns out that there are no fewer men with depression than women. At the same time, in large cities of Russia, the percentage of cases (or rather, those who applied for help) is the same as in the West. If we look at small towns and rural populations, we will see a significant decrease in the number of such patients."

However, it is not worth hurrying to rejoice for the village population. A study by the Institute of Physiology and Fundamental Medicine showed that the risk of depression in the rural population of the Novosibirsk region is not less than that of the urban population. "One of the factors in the development of depression is neuroticism — individual sensitivity to negative experiences," explains Alexander. — High rates of neuroticism are also found in absolutely healthy people. However, the risk of depression in people with increased neuroticism is greater than in people with its low values. In women, neuroticism rates are usually higher than in men. So neuroticism is on average more pronounced in people living in rural areas than in those who live in the city. And Siberian Mongoloids (Yakuts, Tuvinians, Yukaghirs and Evenks) show higher values of neuroticism in psychological testing than Caucasians. For the last fifty years, the rural population of our country has been actively migrating to cities. And then the question arises, who is leaving and who is staying. Most often, there are people in the villages who are afraid of change, afraid of encountering trouble, that is, people with higher neuroticism. As a result, we get such a psychological drift: those who are more prone to depression than others are more likely to stay in the village. It turns out that there are more people with a predisposition to depression in villages than in cities, regardless of their standard of living, salary, etc. At the same time, life in the village is objectively more difficult."

Another thing is how the villagers struggle with depression. As you know, they can turn not to doctors, but to alcohol, which does not relieve them from depression, but only adds problems in life. As a result, villages have a lower percentage of people seeking medical help for depression compared to the city, but a higher rate of suicide, alcohol poisoning, domestic homicide, etc.

A separate question is what depression is. And, as it turned out, a lot of myths are also connected with this issue. For example, many in our country believe that this is just a sad mood or unsolvable problems in life (loss of a job, loss of a loved one). "People with depression often (in our opinion) can have everything in life well — there are no "reasons for sadness". However, they are constantly in a bad emotional state, and the solution of this or that everyday problem does not lead to their recovery," Savostyanov notes. — For example, there is such a concept as "depressive rumination" — recurring obsessive memories, thoughts. I myself have worked with a case where a traumatic episode occurred in a patient more than 15 years ago. Then the man somehow resolved this episode, and for 15 years he did not bother him, and suddenly ... memories began to happen to him, actually depriving him of working capacity. To the point that the memories are so clear that he has to sit down and try to cope with them right where it happened — on the asphalt on the street or on the floor at the workplace. A completely different story is light depression. In this case, the lack of light becomes an irritating event. Women are more sensitive to this type of depression, simply because of the peculiarities of their hormonal system. This is the rare case when changing external conditions really solves the problem of depression. And we do not observe a direct relationship between the risk of depression and, for example, the socio-economic crisis."

Depression is a multifactorial phenomenon. Actually, that is why scientists needed a multidisciplinary team of specialists to study this issue. In addition, Alexander notes: at the level of neurophysiology, it is clear that we call depression a whole group of various diseases that cause a similar "bad" condition.

Currently, Alexander is inclined to assume that in the case of depression, genetic features are imposed on climatic and cultural conditions of life. "To date, it has been established that it is impossible to predict a person's risk of developing any mental illness only on the basis of genetic analysis - genes, especially those associated with behavioral characteristics, always behave differently in different environments."

Nevertheless, during this study, it was possible to find some links between the work of specific genes and the tendency to depression.

"In 1996, a group of researchers led by Klaus-Peter Lesch linked the risk of depression with genetic polymorphisms of the serotonin system," says Alexander. Serotonin is a substance that plays the role of a mediator in nerve cells. In popular articles, it is often called the "hormone of happiness", which, as Alexander notes, is completely wrong. After all, hormones enter the bloodstream, and mediators are released when one nerve cell comes into direct contact with another. At the same time, there is also serotonin in the blood, but it does not directly affect our emotional state. Blood serotonin regulates the gastrointestinal tract and blood clotting. In the brain, serotonin is not associated with a feeling of happiness, but with an arbitrary control of emotions. On a holiday you try to have fun, at work — to be collected and serious, etc. Violations in the serotonin system increase the risk of suicide. Such violations can cause crimes committed as a result of mental illness, as well as depression or anxiety disorders. Serotonin is carried along the nerve fiber by a special protein (serotonin transporter), the structure of which may vary from person to person, which is determined genetically. Simply put, such a protein can be either long (L) or short (S). Genetically, three situations are possible: a person has only a long transporter (genotype LL), only a short one (SS), or both variants at once (LS). Moreover, according to Western studies, in the presence of the LL variant (homozygotes with a more actively working and synthesizing more transporter protein allele), the risk of depression is lower than with other genotypes. But at the same time, according to data obtained in South Korea and Japan, in these countries there is a directly opposite relationship between morbidity and genotype. Japanese and Korean individuals with the LL genotype have an increased tendency to depression. In different regions of China, the relationship between genotype and morbidity varies greatly. In our research, we have obtained different correlations between this allelic polymorphism, personality traits and the risk of developing mental illness for different peoples of Siberia: Russians, Tuvinians, Yakuts and Evenks. We see a complex interaction between a person's genetic characteristics and his living conditions, which can change the influence of a gene, including the opposite.

The results of tests for recognizing emotions (both faces and emotionally colored sentences) turned out to be very interesting. It turned out that people homozygous for the allele of the short serotonin transporter (SS genotype) do not recognize other people's emotions well… This applies to both photos of faces and text. For example, during the experimental tasks, participants were asked to find a spelling error in sentences, some of which described someone else's emotions with a different sign. If people with the LL genotype showed a differentiated brain and behavioral response to sentences of different emotional coloring (different speed, different brain activity), then carriers of the SS genotype were looking for a spelling error, not paying attention to the emotional coloring of the sentence.

"We observed such reactions in all people with a certain genotype, regardless of their ethnicity, living in a big city or village. At the level of brain reaction, there is a clear connection between the carrier of a certain genotype and sensitivity to emotions. But at the same time, when both groups were given a simple game testing the speed of target shooting, carriers of the SS genotype showed significantly higher results: that is, the speed of recognition of non-emotional stimuli, the speed of psychomotor reaction in them is higher than in people with the LL and LS genotypes."

The texts were given to the subjects not only in their native language, but also in a foreign language. Russian Russian Russian Russian speakers had sentences in Russian and English, Tuvinians — in Russian, Tuvan and English, Yakuts tested reactions in Russian, Yakut and English. There was practically no reaction of the brain to the emotional coloring of the English text in all the subjects. For the Tuvan and Russian texts, the Tuvinians had a similar reaction. But the results of the Yakuts, it would seem, are paradoxical: the brain reacted to sentences in English and Yakut as a foreign text, and in Russian as a native language. The researchers see the reason in the fact that the experiment involved mainly students of the university's medical faculty who speak Yakut well, but very rarely encounter written texts in their native language.

Another discovery of these tests: the brain of an indigenous resident of a small Siberian village reacts to a neutral facial expression in the same way as to an aggressive one. "There is nothing surprising in this," Alexander cools my delight and surprise. — A resident of a big city constantly meets with strangers. And the ability to recognize hidden aggression, an implicit threat from another person is a survival factor. In the Tuvan steppe, a stranger is a rarity. And this forces the indigenous people to consider any outsider who clearly does not show emotions dangerous for themselves."


In Caucasians, the probability of encountering an L-allele ("a gene possibly associated with high emotional sensitivity") is 55%, and in Mongoloids — 21%. The probability of encountering an S-allele (possibly associated with reduced emotional sensitivity) in Mongoloids is 73%, in Caucasians — 39%. The occurrence of an allele in the population of more than 70% indicates that it is associated with some kind of adaptive trait. At the same time, in non—urban areas of Yakutia and Tyva, the occurrence of this allele may be more than 90%, while the probability of finding it in a resident of Germany is about 5%.

As a result, in a city where there are many people, the ability to distinguish the emotions of others is a factor that reduces the risk of depression. And in small towns, on the contrary, this ability increases the risks.

Alexander jokingly illustrates the behavior of heterozygotes with an anecdote about the successful name Izyaslav: "Where necessary, he was represented by Glory, and where necessary — Izey." In people born in large cities (for example, in Novosibirsk), carriers of the LS genotype behave like people with high emotional sensitivity, and in Tuvan small settlements — as with low. The question is very relevant, what happens to a carrier of a heterozygous genotype if he moves from a small settlement to a megalopolis, being already an adult. "This is really a very important and relevant question," my interlocutor instantly becomes serious. — We are seeing a significant increase in the Turkic-speaking Mongoloid population in Siberia. If the trend continues, then in 30 years every second inhabitant of a big city will be a Mongoloid. In Tyva, for example, there is a high birth rate (an average of 3.5 children per woman), a dry, uninhabitable climate over a large area and, as a result, active migration from small settlements to large cities. And such migration is alarming because people are adapted to some conditions, but are forced to live in others. This is the reason for the growth of not only psychiatric complications, but also criminal and suicidal episodes." Perhaps this also explains the leading position of Kyzyl (the capital of Tyva) in youth suicides and the high level of domestic injuries.

In reality, according to the expert, no less acute problems arise for the carrier of the LL-genotype, who went, for example, to mine diamonds in Yakutia. Currently, a group of scientists from the Institute of Physiology and Fundamental Medicine plans to examine Russian workers working in shifts in the north of Siberia. "Modern life is such that we constantly have to change our habitat: today you work in Tyva or the Amazon forests, tomorrow — in Moscow or Munich, and it is important to understand what happens to us when we change our habitat," my interlocutor indicates the relevance of research. — That is, we see two ways of social adaptation. The first one, well suited for large cities, is when "you have to think a lot before you do nothing." The second is when it is necessary to move quickly and it is not at all necessary to distinguish the emotions of others."

One of the first problems faced by the team: traditional tests are not suitable for the indigenous peoples of Siberia. For example, the subject may say that he is in a normal mood, and immediately notice that his soul has died…

Depression can be detected not only by the results of surveys and conversations with a psychologist, but also by MRI and electroencephalogram. And, paradoxically, it is best seen in the absence of functional load of the brain. In 2001, an amazing brain system was discovered: in the absence of tasks, it worked actively, when an external load appeared, it froze. The system is called default (DMN). Its disorders are associated with diseases such as senile dementia and autism. Moreover, by the drop in the level of DMN activity, senile dementia can be seen before it manifests itself in behavior. The group in which Alexander works managed to show that the activity of DMN is associated, among other things, with "thinking about social relations." A high risk of depression is usually associated with an increased level of activity of the default system. However, some patients may experience an inverse relationship when the disease is accompanied by the disappearance of the activity of the default system at rest. It is suggested that people with increased activity of the default system have a tendency to rumination and a high sensitivity to negative experiences. The latter are probably more likely to demonstrate a decrease in the ability to have fun.

These deviations are clearly visible on functional MRI and MEG. Gennady Georgievich Knyazev, the scientific director of the project, managed to think of such a mathematical method of data processing that allows you to see the same processes on the EEG And it was extremely important. After all, MRI and MEG, along with a large number of advantages, have significant disadvantages: expensive and immobile. Another thing is an electroencephalogram: "I recently filmed an EEG in a yurt, in the steppe, when the nearest settlement was several tens or even hundreds of kilometers away. And I can shoot on a stump in a remote taiga," Savostyanov gives examples. There are other significant advantages of EEG: its time resolution is two milliseconds versus a few seconds for a tomograph.

An interesting question is what happens to a person's brain when the latter begins to be treated for depression. "Most likely, the treatment starts the process of rethinking traumatic events," explains Alexander. — For example, to combat rumination, there are two methods: the first is to try to forbid yourself to think about bad events (this method does not lead to anything good, depression only intensifies), the second is to overestimate the event in a positive way (tore off a leg, but remained alive). Almost all religious psychotherapy is options for rethinking negative experiences — such that a person sees some higher, positive meaning in bad events. Moreover, people who come out of depression have a decreased susceptibility to both positive and negative emotions. But at the same time, a lot of energy is spent on "inner speech", the processes of rethinking. That is, in fact, during treatment, a patient may begin to differ from a healthy one even more than before therapy, but such differences are associated with the process of his recovery."

So far, the participants of the research group have more questions than answers. And while the research remains purely scientific. According to Alexander, one can hope for practical results in five years: early diagnosis, personalized selection of treatment (today drugs for depression help only in about 70% of cases, and 10% worsen the patient's condition). "Currently, we have a large mosaic in front of us; we have already collected some puzzles and see part of the picture, we assume something, we have yet to learn something. Many doors are already open, but now we need to find out what is behind them," Alexander Savostyanov ends our conversation very romantically.

Portal "Eternal youth" http://vechnayamolodost.ru  31.03.2017

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