MicroRNAs as biomarkers of resilience or vulnerability to stress

- MicroRNAs in blood are associated with future vulnerability or ongoing resilience.
- MicroRNAs in the medial prefrontal cortex are associated with vulnerability.
- MicroRNAs in the basolateral amygdala do not differentiate vulnerability from resilience.

Identifying novel biomarkers of resilience or vulnerability to stress could provide valuable information for the prevention and treatment of stress-related psychiatric disorders. To investigate the utility of blood microRNAs as biomarkers of resilience or vulnerability to stress, microRNAs were assessed before and after 7 days of chronic social defeat in rats. Additionally, microRNA profiles of two important stress-regulatory brain regions, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), were assessed. Rats that displayed vulnerability to subsequent chronic stress exhibited reductions in circulating miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p, and miR-532-5p levels. In contrast, rats that became resilient to stress displayed reduced levels of miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p compared to controls. In the mPFC, miR-126a-3p and miR-708-5p levels were higher in vulnerability compared to resilient rats. In the BLA, 77 microRNAs were significantly altered by stress but none were significantly different between resilient and vulnerable animals. These results provide proof-of-principle that assessment of circulating microRNAs is useful in identifying individuals who are vulnerable to the effects of future stress or individuals who have become resilient to the effects of stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the BLA are regulators of resilience/vulnerability to stress.