New research suggests the reason some people develop post-traumatic stress disorder while others do not may be because of molecular changes, specifically alteration in micro-RNA as related to gene regulation.
In a controlled study involving military personnel on deployment to a combat zone in Afghanistan, researchers from the Netherlands discovered evidence that blood-based miRNAs may be biomarkers for symptoms of PTSD.
The new discovery may offer an approach towards screening for symptoms of PTSD, and holds promise for understanding other trauma-related psychiatric disorders. However, given the small pilot study design, the findings will need to be validated, extended, and confirmed.
PTSD is a psychiatric disorder which can manifest following exposure to a traumatic event, such as combat, assault, or natural disaster. Among individuals exposed to traumatic events, only a minority of individuals will develop PTSD, while others will show resiliency.
Little is known of the mechanisms behind these different responses. The last few years have seen much attention given to whether the modification and expression of genes — epigenetic modifications — might be involved. But 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.
In the new study, researchers worked with just over 1,000 Dutch soldiers and the Dutch Ministry of Defense to study changes in biology in relation to changes in presentations of symptoms of PTSD in soldiers who were deployed to combat zone in Afghanistan.
In the longitudinal study investigators collected blood samples before deployment, as well as six months after deployment. Most of the soldiers had been exposed to trauma, and some of the soldiers had developed symptoms of PTSD.
MiRNAs (micro ribonucleic acids) 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 they do not code; in other words, they do not specify the production of a protein or peptide.
However, they have very important roles in biology (every miRNA regulates the expression, and thereby also the activity of several other genes), and they are known to regulate the impact of environmental factors on biology. In addition, brain-derived miRNA 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, and even alcoholism. This regulatory role makes them also a candidate for investigation in PTSD.
“We discovered that these small molecules, called miRNAs, are present in different amount in the blood of persons suffering from PTSD compared to trauma-exposed and control subjects without PTSD,” said first author Dr. Laurence de Nijs (Maastricht University).
“We identified over 900 different types of these small molecules. 40 of them were regulated differently in people who developed PTSD, whereas there were differences in 27 of the miRNAs in trauma-exposed individuals who did not develop PTSD.”
“Interestingly, previous studies have found circulating miRNA levels to be not only correlated with different types of cancer, but also with certain psychiatric disorders including major depressive disorders.”
However, the researcher cautions that several steps need to be performed before such results can really have an impact on the larger field and in clinical practice. Nevertheless, the discovery of biomarkers may also provide novel information about the biological mechanisms underlying the development of PTSD.
“Most of our stressful experiences don’t leave a long-lasting psychological scar. However, for some people who experience chronic severe stress or really terrible traumatic events, the stress does not go away. They are stuck with it and the body’s stress response is stuck in ‘on’ mode. This can lead to the development of mental illness such as PTSD,” de Nijs said.