29 May 2008

"Genes of alcoholism" and adequate self-esteem

Nadezhda Markina, " <url>"What role does genetic predisposition play in the development of alcoholism?

What genes are involved in the formation and maintenance of alcohol dependence? Can gene analysis predict a possible predisposition to alcoholism? What can parents do to prevent their child from becoming an alcoholic? We talked about this with Svetlana Alexandrovna Borinskaya, a well-known Russian geneticist, Candidate of Biological Sciences, a leading researcher at the Genome Analysis Laboratory of the Vavilov Institute of General Genetics of the Russian Academy of Sciences.

There is an opinion that in Russia they always drank a lot and from this they lived less than they should.First of all, I would like to object: in Russia, they didn't always drink a lot.

Previously, they did not drink vodka, but mead and other drinks, no stronger in strength than beer. This is the primordial tradition, and the current situation is an acquisition of the XX century, and to a very strong extent – of the Soviet era. Some other countries, for example, England, also went through a period of violent heyday of drunkenness a hundred years ago, but suspended it by state measures.

There is a clear correlation between the level of alcoholism and the changing social situation in Russia. So, Doctor of Medical Sciences, Head of the Department of Informatics and Systems Research of the Research Institute of Psychiatry of Roszdrav Alexander Nemtsov compared the dynamics of real alcohol consumption, which according to expert estimates is higher than official data, and the change in the death rate in Russia. It turned out that these charts are pretty much the same: both lines fall during Gorbachev's "anti-alcohol company" in 1985 and creep up with the beginning of market reforms in 1992.

According to Alexander Nemtsov, about a third of all deaths of men of working age in Russia are directly or indirectly related to alcohol. This is ten times higher than the official statistics of the State Statistics Committee of the Russian Federation (3% of alcohol from the total number of deaths). The reason for this discrepancy, in his opinion, is that official statistics do not fully take into account even direct losses when the cause of death is taking doses of alcohol incompatible with life, and does not take into account a much larger number of cases when alcohol is the cause of accidents, injuries, murders and suicides, diseases, etc.

All these facts testify in favor of the fact that alcoholism, first of all, is a social disease. And yet, against the background of such a powerful dependence on external conditions, to what extent does alcoholism depend on genes?Alcoholism is a disease whose causes are multifaceted.

It often has a family character, as well as mental illnesses: manic-depressive psychosis, depression, schizophrenia. To establish the nature of hereditary predisposition to alcohol, studies were conducted in families, twin studies and studies of adopted children. A comparison of alcoholism in identical and fraternal twins showed that the role of heredity is quite large. Adopted children tend to develop alcoholism more like their biological parents, not adoptive ones. This shows that genes influence the predisposition to alcoholism. However, there is no one gene that is responsible for the propensity to alcohol. The identified "risk" genes manifest themselves differently depending on the environment - the situation in the family and in society.

It is clear that there is no single "gene of alcoholism". But is it known which genes, one way or another, are associated with alcoholism?Researchers have identified two groups of such genes.

Firstly, these are genes that control the metabolism of alcohol in the body. And secondly, genes that control neuropsychic functions.

What happens in the body after taking alcohol? Ethanol is oxidized in two stages, and two key enzymes work in these two stages. First, under the action of the enzyme alcohol dehydrogenase, ethanol turns into acetaldehyde, and that under the action of the enzyme acetaldehyde dehydrogenase turns into acetate (to make it clearer – eventually, alcohol turns into vinegar, but with the formation of an intermediate toxic substance – acetaldehyde). The speed of these enzymes is genetically determined and it is influenced by different variants of both genes.

In the 70s, the population of Southeast Asia - the Chinese, Koreans and Japanese, discovered the so-called "flush syndrome" (from the English flush – a rush of blood, blush) - after a small amount of alcohol they became ill: heart palpitations increased, blood pressure rose, and they could not drink more. It turned out that they have inactive mitochondrial acetaldehyde dehydrogenase, and alcohol dehydrogenase, on the contrary, is very active. As a result, ethanol is rapidly converted into acetaldehyde, and that, in turn, is broken down very slowly. Namely, acetaldehyde causes unpleasant symptoms and poor health in a person after drinking alcohol.

For most Europeans, the opposite happens: the first stage of oxidation is slow, and the second is fast. The "European" and "Asian" variants of enzyme genes differ by only one nucleotide. If a person has both acetaldehyde dehydrogenase genes received from mom and dad presented with "Asian" versions, he simply cannot drink such an amount of alcohol to become addicted. That is, such a combination is a protective genotype in relation to alcoholism.

The "Asian" variant of the alcohol-dehydrogenase gene (also known as the "Asian" variant of the acetaldehyde-dehydrogenase gene) has a protective effect against alcoholism, but is more weakly pronounced. In Southeast Asia, more than 70% of the population has it, in the Middle East - about half, in Europe – up to 5-8%. Interestingly, the frequency of occurrence of the Chukchi is the same as that of Europeans. Contrary to popular belief, they do not differ from, for example, Russians, in these enzymes.

Prior to the discovery in the 1970s of these genetic differences between the populations of different countries, the smaller amount of alcohol consumed in some countries was attributed solely to social conditions. Now it is clear that there is a genetic contribution here. However, social conditions cannot be ignored. In the Middle East, genetic features are combined with a cultural (religious) prohibition on alcohol. However, at least one of the groups of Middle Eastern origin – Jews – does not have such a strict religious prohibition. Nevertheless, Jews consume smaller doses of alcohol than European peoples, and alcoholism is less common among them. A study conducted in Israel of different groups of migrants from Europe shows that Jews who came from Russia consume more alcohol than immigrants from other countries. They do not differ genetically from each other – the frequency of the projective variant of alcohol dehydrogenase in different groups of Jews is close. It is assumed that these differences reflect sociocultural attitudes towards alcohol in different countries.

In Africa, variants of another part of the alcohol-dehydrogenase gene are associated with alcoholism. A point mutation was also found in this site – the replacement of a single nucleotide. African-American mothers who do not drink and drink "more than one drink a day" were studied and the condition of their children at the age of one year was assessed. It turned out that in non-drinking mothers, the genotype did not affect the level of development of the child. And in drinkers, carriers of the mutant gene were protected from the effects of alcohol – their children did not lag behind the children of non-drinking mothers in development. At the same time, the children of drinking mothers with the usual gene were less developed intellectually and physically.

What happens in the human brain when drinking alcohol? How similar is this condition to the condition after taking drugs?When drinking alcohol, the positive reinforcement system is activated in the brain, which includes the structures of the so-called limbic system of the brain and the prefrontal cortex.

Activation of this system leads to the repetition of actions that cause pleasure. The brain structures included in the positive reinforcement system are also activated when using drugs, for example, cocaine, amphetamines, marijuana, but alcohol acts more widely, involving other areas of the brain, including the cerebellum, responsible for maintaining balance and coordination of movements.

Moreover, alcohol and drugs interfere with the work of the training system, so that the effect of so-called "over-training" appears against their background. In the areas that are targets for alcohol, new contacts between cells are formed – new synapses. When forming an addiction, instead of providing normal learning for something useful, these structures reinforce pathological behavior. Brain structures involved in normal learning, memory, are "recruited" to ensure the action of a chemical agent. At the same time, brain resources are diverted from maintaining normal life processes and begin to engage in the formation and maintenance of alcohol dependence.  

And what genes are involved here?Many genes are involved in the formation of alcohol dependence that control the transmission of a nerve impulse from one neuron to another through intercellular contact – synapse.

These are the genes of synthesis and degradation of neurotransmitters such as dopamine, serotonin, gamma-aminobutyric acid, the genes of their receptors and carriers. There are many genes, all of them contribute, although the role of each individual gene is not so great.

For example, it has been shown that a certain variant (TaqA1 allele) of the dopamine receptor gene DRD2 is more common in alcoholics. In this variant of the gene, the density of receptors decreases.

There is also the monoamine oxidase (MAOA) gene, which is an enzyme that destroys dopamine that has not reacted in the synaptic cleft. A mutation in a gene – the replacement of one nucleotide with another, leads to low MAOA activity, which makes behavior more unstable, sometimes manifesting as antisocial behavior. But all these features are fully manifested in dysfunctional families. In the same place where everything is fine with upbringing, the influence of the gene is corrected, and carriers of the mutant gene (with low MAOA activity) exhibit antisocial behavior no more often than carriers of the gene with normal activity.

A similar situation is with the transporter gene of another neurotransmitter – serotonin. One of the variants of this gene, in which an insufficient amount of the transporter protein is formed, is associated with a tendency to depression and, accordingly, to alcoholism. But it manifests itself under unfavorable conditions of upbringing, and where a child is brought up in love and understanding, the "bad gene" does not make itself felt.

The predisposition to alcoholism also involves genes responsible for contacts between cells, for the formation of ion channels, and many others. They find new ones all the time. For example, when studying the electrical activity of the brain, it turned out that in people with an irregular alpha rhythm (the main rhythm of the EEG - electroencephalogram of a person in a calm state) after drinking alcohol, it became more pronounced. This was accompanied by relaxation, which did not occur in such people without alcohol. The genes responsible for this effect have also been found – the gamma-aminobutyric acid receptor (GABA) gene and others.

New approaches to brain research, such as functional magnetic resonance imaging, positron emission tomography, provide new knowledge about the processes that occur under the influence of alcohol and, accordingly, allow us to identify new genes associated with these processes and alcoholism.

In total, dozens of genes have been found to date, the disruption of which is supposed to increase the risk of alcoholism.

What practical significance can our knowledge of the "genes of alcoholism" have? Can we predict the risk of this disease by genetic analysis? Knowledge of such genes gives us new information about the nature of the disease, in this case alcoholism.

Opportunities are opening up for the creation of new drugs, because targets for alcohol can be targets for medicinal substances to the same extent. Finally, it will be possible to predict the risks of alcoholism in people who carry any "dysfunctional" genes, but many more studies need to be conducted for such predictions. Of course, today it hardly makes sense to genetically examine all children for whether they will become alcoholics in the future. And it is hardly to be expected that drugs alone can get rid of alcoholism. But a hereditary predisposition to the disease manifests itself if both genes and the environment act in the same direction. We can't change genes yet, but we can change the environmental conditions to reduce the risk.

Genetic studies of alcoholism suggest what preventive measures can be taken. Here we can talk not only about the creation of new drugs, but also about pedagogical measures. For example, a recent study of carriers of the above-mentioned "risky" variant of the dopamine receptor gene (DRD2 TaqA1) showed that they are less sensitive to negative reinforcement than carriers of another variant of the gene. They simply do not include the structures responsible for remembering the negative results of their choice. In other words, they are capable of repeatedly stepping on the same "rake", they do not have a mindset to avoid actions that entail unpleasant consequences for them. It can be assumed that in the upbringing of such children, praise for "good" behavior, repeated consistently and patiently, is more effective, and punishment may not work or give negative results. Geneticists, as well as doctors and psychologists, are trying to understand why people are different, and their approaches complement each other.

What is the main thesis that parents reading our interview should learn? The output is simple:

if you don't want your children to become alcoholics, pay attention to their upbringing! They say that alcohol advertising can be seen at every turn, but how many people know that there are quite effective programs for the prevention of alcoholism and drug addiction developed for schools? They are based not on rhetorical statements about the harm of addictions, but on the development of adequate self-esteem among students, the ability to recognize and assess the consequences of risky behavior.

A comprehensive approach is needed here – programs for the prevention of alcoholism and drug addiction, promotion of a healthy lifestyle, joint efforts of the family, psychologists, teachers, doctors, and the state.

See alsoAndrey Korotaev, Daria Khalturina.


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