Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans

Abstract

Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.

microRNA mir-598-3p mediates susceptibility to stress-enhancement of remote fear memory

“…The memory-, SS-and sex-specific effect of mir-598-3p manipulation suggests that the functional pathways targeted are specifically related to the impact of stress on memory. Interestingly, a precursor miRNA family, mir-19b, has been implicated in PTSD [20,21] and is differentially expressed between SS and SR mice in our own laboratory. This same miRNA is enhanced in the amygdala following chronic social defeat stress and mir-19b in vivo manipulation bidirectionally modulated cued fear conditioning without altering contextual fear memory or anxiety-like behavior in the OFT, dark/light transfer test, or the EPM [14].…”

“…We focused our analyses on the basolateral amygdala (BLA) because of the known contribution of this region to fear learning and memory storage at remote time points [16][17][18][19] We recently demonstrated that exposure to a single acute stressor (120 minutes of restraint stress) induces a change in the molecular profile of the BLA, including differential expression of 18 miRNAs an entire month after stress [5]. Differential miRNA expression has also been reported in the serum of patients with PTSD [20] [21] and between rats selectively bred for high or low stress reactivity [22]. The behavioral consequences of stress exposure have also been linked to miRNA function in the amygdala in several reports.…”

Noncoding RNAs: Stress, Glucocorticoids, and Posttraumatic Stress Disorder

“…Fifth, miR-21 upregulation in veterans with PTSD was reported in a non-miRNA-specific microarray study (70). Among these studies, miR-15b downregulation was reported by two studies (66,67). miR-15b is also associated with multiple cancers (71); is a potential biomarker for Alzheimer's disease (72), which is interesting as PTSD increases risk for dementia (73); and is involved in GC signaling (see Putative Role of ncRNAs in GR Signaling in PTSD).…”

“…Four cross-sectional miRNAs studies in PTSD patients and control subjects and one array-based total RNA study yielded divergent results, with little overlap in modulated miRNAs between studies (Table 3). First, a miRNA signature in military PTSD, comprising 8 significant multiple-comparison corrected hits, was discovered, with hits associated with biological pathways involved in axonal guidance and cancer (66). Second, 71 miRNAs, exhibiting differential regulation in control subjects versus PTSD patients, some of whom also had depression, were reported (67).…”

Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?

“…To this end, miR-203a-3p derived from extracellular vesicles was upregulated, whilst miR-339-5p was downregulated in a cohort of PTSDs patients compared with controls [ 52 ]. Differentially expressed circulating miRNAs associated with PTSDs were detected in another study focused on stress-related disorders in the population of military veterans [ 53 ].…”