Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can manifest itself following exposure to a threatening traumatic event such as combat, assault or a natural disaster. The disease is characterized by symptoms including re-experiencing of the traumatic event through flashbacks or recurrent nightmares, constant avoidance of reminders of the event, negative mood, and extreme arousal. These symptoms can manifest itself through insomnia or hyper-alertness and may last for a very long time, which significantly affects the quality of life of PTSD patients. Individuals with PTSD are six times more at risk of committing suicide and having marital problems, and the annual loss of productivity is estimated to be approximately $3 billion. Currently, there is no definite cure for patients with PTSD, and available treatments often are not effective.
Within the general population, it is relatively common to be exposed to a traumatic event over the course of one’s lifetime (40–90%), but only a fraction of individuals (7% and 12%) will develop PTSD while others will adapt to the situation and maintain proper mental health. The identification of markers that distinguish persons at high and low risk of developing PTSD following trauma exposure would enable more effective preventive strategies and early interventions.
Little is known regarding the mechanisms behind these different responses. During the last few years, increasing attention has been given to whether the modification of genes expression in the form of epigenetic mechanisms might be involved. Among epigenetic mechanisms, microRNAs (miRNA, Micro RiboNucleic Acids) are gaining attention. MiRNAs are small molecules with chemical building blocks similar to DNA. Unlike the more famous DNA, miRNAs are typically very short – comprising only around 20 to 25 base units (the building blocks of nucleic acids), and are non-coding. In other words, they do not specify the production of a protein or peptide. However, they have very important roles in biology since every miRNA regulates the expression, and thereby also the activity of several other genes, and are known to regulate the impact of environmental factors on biology. In addition, brain-derived miRNAs can circulate throughout the human body and can be detected in the blood. Differences in miRNA levels have been associated with certain diseases, such as some cancers, kidney disease, alcoholism and even depression. This regulatory role makes them a candidate for investigation in PTSD. However, there are several practical and ethical challenges in designing a research study on humans undergoing such experiences, meaning that designing relevant study approaches is difficult.
Based on this and the emerging role of miRNAs as key epigenetic players in psychiatric disorders, we aimed to determine the role of miRNAs in the susceptibility for developing PTSD after being exposed to traumatic stress. More specifically, the two key objectives were (1) to identify miRNA candidates associated with differential susceptibility to develop PTSD after traumatic stress exposure in humans and mice and (2) to test the effect of manipulating the expression of candidate miRNAs on the susceptibility to traumatic stress exposure in mice.
