The concept of endophenotypes

Biologist Dr. Doping tells about studies of mental disorders, disease modeling and audiogenic epilepsy in mice and humans. What is endophenotype? How to identify endophenotypes helps in the diagnosis of schizophrenia? How endophenotypes concept will find general principles of abnormalities in the brain?

Diseases of the central nervous system that are presumed genetic basis - is one of the weak points of modern medicine. And in dealing with so many problems in this direction to help studies on the so-called genetic models. Genetic model reproduces certain characteristics of the disease, is the disease some common internal mechanisms.

Even in the middle of the XX century, Gould and Gottesman, US researchers have formed the concept of the so-called endophenotypes that helps an integrated assessment of what gives us a model in relation to the disease that this model tries to reproduce. In endophenotypes simpler inheritance than the actual mental illness because mental illness in the families of people is caused not only by genetic factors, but a number of features endogenesis, features the history of the person, the peculiarities of his upbringing and environment in which it resides in adulthood . endophenotypes concept tries to describe what is happening in the brain the same way in the simulation of the disease, and in fact when mental illness in humans.

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The concept of endophenotypes and attracts the attention of researchers that healthy relatives of the mentally ill people can detect symptoms that do not end the disease. You can search for similarities in concepts of past generations of researchers, in particular, Sergei Davidenkov, differ very much basic, "big" and micro-features of disease that can manifest itself with relatives and are not mentally ill. And a logical development of this kind of views and was the concept of endophenotypes.

Regarding the features of behavior and psyche, the human intellect, this concept is terribly interesting and promising but relatively intelligent changes, it is still not very developed. However, researchers have many great mental illness use device that provides the concept of endophenotypes in order to delineate more clearly the signs of movements in patients, is the change in modeling the disease in animals....

In particular, schizophrenia - is multifaceted, a terrible disease that is associated with profound violations of human cognition. But it appears that these patients have a more simple and physiological symptoms which are also reproduced in animal models. In particular, so-called pre-pulsebraking startle response. Startle reaction - a wince on unexpectedly strong stimuli - tactile stimulation or sounds. It turned out that if before a strong incentive to give weaker stimulus, the startle response to a subsequent strong stimulus wanes. And it turned out that it is possible to find a genetically characterize the line of laboratory animals in which there is such a violation. They weakened it pre-pulse braking, and it also is impaired in patients with schizophrenia - a clear, maybe even a diagnostic criterion where it is difficult to distinguish between cases of a schizophrenic psychosis and psychosis. And it turns out that there are still signs - breach of certain features of perception, visual perception.

Cognitive impairment - this is difficult, but, most importantly, describes protein Reelin, which is active in the formation of the nervous system, it determines the regularity neuronal precursor migration in the cerebral cortex. And there are mice in which it is broken, it is possible to obtain strains of mice in which the gene is disrupted by molecular genetic methods. And it turns out that Rilin function in patients with schizophrenia is also violated.

Here we see that the animal model reveals signs of the blocks, which are characteristic of this disease.

But there is still described about seven, perhaps even more genes whose expression is impaired in patients with schizophrenia and impaired expression of which in the experiment also leads to such simple features included as an integral part in endophenotype schizophrenia. This shows that this concept - even though she's still not very well known to biologists and maybe even many psychiatrists - a vital perspective, because it exposes the theoretical framework in order to be able to more clearly describe the symptoms of the disease and the modeling of these symptoms experiment.

Now we are aware of other examples endophenotypes. There is such a phenomenon as audiogenic epilepsy rodents: in response to a strong sound in mice and rats - not all, but a number of genotypes - developing convulsive state. It manifests itself in the form of successive change of phases where the first phase - a mad race with jumps, which gradually ends clonic seizures. Clonic seizures - a muscle twitching limbs first, then the whole body. And then they move to the tonic convulsions, in such a powerful tension, stretching the whole body of the animal. In mice, rats of different lines obtained in different laboratories, based on different starting populations, this feature is absolutely the same picture. This speaks in favor of the fact that this is endophenotype audiogenic epilepsy.

Audiogenic epilepsy as such a person generally does not occur or is in the form of seizures in response to a strong sound - you need to try very hard, so you got such a strong sound to have seizures. But, unfortunately, the described cases, when young people who abuse loud music through headphones, this kind of things happen - there is a predisposition seems. But the course of tonic seizures that are characteristic of human stem seizures of epilepsy, it is very important for the models. And endophenotype audiogenic epilepsy - this is just an example of what can and should be studied in the study of mechanisms of convulsive states. And it shows that the concept of endophenotypes - this is what should have been, perhaps, describe the level of exact sciences.

Endophenotypes concept was born as part of behavioral genetics. And genetics of behavior and Neurogenetics in their modern sound - this is an extremely important area, which, in principle, in my opinion, given not as much attention as it should, not least because it is, as a rule, are private and little related to each other work, and there must be some generalizing ideas. Generalizing ideas about the role of genotype in the formation of deviations from the norm - this idea, in my opinion, it should be more clearly expressed in the theoretical constructs, and the conclusions that are made from a large number of experimental studies. Such research is very much, but the concept of endophenotypes is likely to be useful to evaluate it all and find some general principles of abnormalities in the brain. But you need to be familiar with the limits of the normal variability of the brain, which is also, in general, are not well defined and not very well known.