MicroRNAs present in neuron-derived extracellular vesicles extracted from the blood of psychiatric patients as potential biomarkers of mood disorders

Mood disorders, including major depressive disorder (MDD), are still a considerable burden for modern society. Despite the availability of approx. fifty different drugs, the treatment of MDD is far from ideal, nor is the full understanding of the mechanism of action of antidepressant drugs (ADs) administered repeatedly (which is necessary to achieve clinical efficacy). There have been several hypotheses explaining the etiopathogenesis of depression. Most of these are based on the mechanisms of action of known ADs, the first of which were discovered by serendipity in the 1950s (imipramine and iproniazid). Later, the mechanism of their acute action (e.g. non-selective inhibition of re-uptake of serotonin and noradrenaline, and inhibition of monoamine oxidase, respectively) has been elucidated, and most of the newly synthesized compounds mimic some or all of their features: being either more selective towards one of the biogenic amines, having an affinity towards various neurotransmitter receptors such as N-methyl D-aspartate (NMDA) receptors for glutamate, or being more selective and reversible monoamine oxidase inhibitors (1). Knowing these mechanisms does not help in achieving a satisfactory clinical outcome, in fact, we still do not understand the etiopathology of MDD and other mood disorders. Most of the numerous behavioral, biochemical, and molecular preclinical studies focus on various kinds of stress since it is regarded as the main factor contributing to mood disorders. Stress is defined as a condition that seriously perturbs the psychological and physiological balance of an individual. Traumatic stress, however, does not affect everyone in the same manner—some susceptible individuals (not only humans but also animals) adapt poorly to stressors and express inappropriate responses that can become persistent states of stress themselves. Resilient individuals can perceive adversity and develop adaptive psychological and physiological responses. The underlying mechanisms of these responses are not fully understood, although they are known to depend on a combination of genetic and non-genetic factors that interact in complex ways. Similarly, lack of response to ADs treatment is very often encountered, despite continuous improvements in treatment recommendations and alternatives to convention pharmacotherapy, including psychotherapy and deep brain stimulation as well as augmenting agents (e.g., atypical antipsychotic drugs or lithium). We still do not know what is the mechanism of such diversity of responses, therefore finding biomarkers useful in the identification of patient subpopulations—potential treatment responders vs. nonresponders, not to mention biomarkers useful to distinguish bipolar from MDD patients—is of utmost importance. The idea that circulating microRNAs (miRNAs) might be a good indicator of processes underlying psychiatric illnesses is present in the scientific literature for some time (2). The first miRNA was discovered in 1993 (3) while studying the development of C. elegans. Since then, many families of these small oligonucleotides have been identified. miRNAs molecules, widely expressed in eukaryotes, are small (17–24 nucleotides), non-coding RNA transcripts that play important role in the post-transcriptional regulation Editorial Commentary