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Posttraumatic stress disorder (PTSD) - a complex mental disorders developing in some (but not all) people after severe traumatic experiences. American scientists have found that the likelihood of developing PTSD in women is partly hereditary nature and depends on the gene that affects the sensitivity of cells to one of the "stress hormone." The activity of this gene depends on the level of estrogens (female sex hormones). Opening the key to understanding the causes of the increased tendency of women to PTSD and can help in the development of new products for its treatment.

"Pituitary activating peptide adenylate cyclase» (Pituitary adenylate-cyclase activating polypeptide, PACAP) - one of the hormones that regulate the body's response to stress mammals. PACAP is a peptide of 38 amino acids. It is synthesized in the central nervous system, especially in the limbic system of the brain (see lymbic system), as well as immune cells, gonads, adrenal glands, gastrointestinal tract and other organs and tissues. Neurons and other cells of the organism perceive this signal peptide using a special receptor PAC1.

PACAP functions are many and varied (they are not limited to the regulation of the stress response), but detailed study of them are only a few. In particular, there is still much uncertainty remains on the question of the role of the signaling system in the PACAP-PAC1 psychological (and not only physiological) people's reactions to severe stress factors.

A large team of American neuroscientists, doctors and psychologists set out to find out if there is a connection between the PACAP-PAC1 and the formation of post-traumatic stress disorder (PTSD), or post-traumatic stress syndrome - a complex mental disorders that develop in some people after severe traumatic experiences. The study is published in the latest issueNature.

PTSD can be a cause of severe physical trauma (for example, received in a car accident), participation in hostilities, maltreatment in childhood sexual abuse. People suffering from PTSD can not get rid of the obsessive fears associated with memories of experienced events.

Fortunately, the majority (approximately 80-90%) of survivors of severe traumatic events, some time recovering and getting back to normal life. PTSD develops only the remaining 10-20%, while women are prone to this disease to a greater extent than men. At the same force traumatic impact the likelihood of developing PTSD in women is about twice higher than that of men. Until now, very little is known about the genetic and physiological factors that affect the likelihood of developing PTSD. It previously identified risk factors include reduced volume of the hippocampus and some anomalies in the amygdala and the island (see: insular cortex). Lack of scientific data hinders the development of effective treatments for PTSD. Available to medical facilities - psychotherapeutic treatments and antidepressants - help only a small proportion of patients.

The authors compared the severity of PTSD symptoms to the system state PACAP-PAC1 in a large sample of Americans have experienced severe traumatic events. In the diagnosis of PTSD symptoms using three groups: 1) constant intrusive recollections of the trauma experienced, 2) avoidance of all that is associated with a traumatic event, 3) hyperexcitability, manifested, in particular, increased fearfulness. Depression that often accompanies PTSD is not included in its composition and is considered as a separate phenomenon.

Statistical analysis of the results, of course, take into account age and sex differences, and the nature and severity of injuries. The study showed a close relationship between PTSD and system PACAP-PAC1, and this connection is much more clearly pronounced in women than in men.

Scientists have discovered that women (but not men) strong positive correlation between the level of PACAP in the blood and the severity of all three groups of symptoms of PTSD. Symptoms of depression, however, does not depend on the level of PACAP. This result indicated that researchers are on the right track and the system PACAP-PAC1 really has something to post-traumatic syndrome.

The authors then undertook a targeted search of hereditary (genetic) factors that affect the risk of developing PTSD. For this we studied the genes encoding PACAP hormone receptor and PAC1, in 1237 patients who survived severe injuries. Were analyzed in a total of 44 variable nucleotide positions (see single nucleotide polymorphisms) present in these two genes: the gene 14 and 30 hormone receptor gene.

After all the necessary statistical adjustments revealed that one (and only one) of these SNPs significantly affect the likelihood of developing PTSD (but not depression) after a traumatic event. Moreover, as in the case of the PACAP in the blood level, this dependence was found only in women.

The development of post-traumatic syndrome in women depends on the genotype.Height of the barsreflects the average severity of PTSD symptoms.The horizontal axis - Genotype. Figure of the article under discussion inNature

In women who have a certain position in the PAC1 receptor gene nucleotide C (cytosine), the likelihood of developing PTSD after a traumatic event was significantly higher than that of women who are in this position nucleotide G (guanine). More precisely, women with CC genotype have a maximum risk of developing PTSD, with the TT genotype - medium, with genotype GG - minimum (see figure).

The authors then analyzed the nucleotide sequence of the gene region receptor PAC1, which is currently a single nucleotide polymorphism. It turned out that this portion of the gene is similar to the so-called estrogen-effector elements (oestrogen response elements, EREs) - DNA fragments, which are mediated by the activity of genes can be regulated by female sex hormone estrogen.

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