Circulating microRNAs as potential biomarkers of differential susceptibility to traumatic stress and their possible implication in the efficacy of Mindfulness-Based Programs

Epigenetic regulation of gene expression has been largely studied for its implication in neuronal processes, including brain development and plasticity. Beside the most well-characterized epigenetic mechanisms, such as histone protein modification and DNA methylation, microRNAs (miRNAs) are emerging for their involvement in long-lasting behavioral and mental effects occurring in psychiatric disorders. What we learn from previous neurobiological studies is that differential expression profiles of miRNAs exist in subjects with mental illness compared to health controls. Recently, the discovery of circulating miRNAs in biofluids has brought great advantages for clinical diagnosis. Most importantly, circulating miRNAs have been proved to reflect the differential expression encountered in diseased tissues by their differential enrichment throughout body fluids. This has led to consider the potential usage of circulating miRNAs as biomarkers of brain-related disorders. Up to date, miRNA profiling of psychiatric disorders has mainly regarded schizophrenia and Major Depressive Disorder. However, less is known about Post-Traumatic Stress Disorder (PTSD), which is a psychiatric disorder that can develop following exposure to or witnessing an authentic or even potential life-threatening event. The fact that only part of the population of individuals exposed to trauma will develop PTDS leads to classification of phenotypes as susceptible or resilient phenotypes. The present thesis consists of two studies. 1-The first study aimed to identify, among circulating miRNAs, potential biomarkers of susceptibility or resiliency to traumatic stress. For this purpose, serum samples collected from a cohort of military soldiers (N = 89), scheduled for a deployment of 4 months in Afghanistan, were examined. Next Generation Sequencing was performed in a subset of the military cohort (N = 24) composed of soldiers that were selected after being characterized for their exposure to stress and for the level of susceptibility to PTSD. The differential miRNA expression profile obtained from the sequencing was then validated by means of quantitative real-time PCR, both in the entire military cohort and in social defeat stress mice (N = 23), both subdivided in susceptible and resilient to traumatic stress subjects and non-exposed to trauma controls. 2-In the second study, we wondered whether expert meditators could be characterized by a miRNA profile which resembles the expression pattern in resilient individuals. In fact, Mindfulness-Based Program (MBP) is being confirmed as an efficient behavioral approach to both prevent and counter damaging effect of stress-exposure. Therefore, we examined the expression profile of circulating miRNAs in plasma samples from a group of expert meditators and controls (N = 15). Although several miRNAs were identified as potentially interesting biomarker candidates, future and larger studies are needed to resolve obtained issues and confirm the current findings.