Noncoding RNAs: Stress, Glucocorticoids, and Posttraumatic Stress Disorder

Abstract Posttraumatic stress disorder (PTSD) is a pathologic response to trauma that impacts ∼8% of the population and is highly comorbid with other disorders, such as traumatic brain injury. PTSD affects multiple biological systems throughout the body, including the hypothalamic-pituitary-adrenal axis, cortical function, and the immune system, and while the study of the biological underpinnings of PTSD and related disordersare numerous, the roles of noncoding RNAs (ncRNAs) are just emerging. Moreover, deep sequencinghas revealed that ncRNAs represent most of the transcribed mammalian genome. Here, we present developing evidence that ncRNAs are involved in critical aspects of PTSD pathophysiology. In that regard, we summarize the roles of three classes of ncRNAs in PTSD and related disorders: microRNAs, long-noncoding RNAs, and retrotransposons. This review evaluates findings from both animal and human studieswith a special focus on the role of ncRNAs in hypothalamic-pituitary-adrenal axisabnormalities and glucocorticoid dysfunction in PTSD and traumatic brain injury. We conclude that ncRNAs may prove to be useful biomarkers to facilitate personalized medicinesfor trauma-related brain disorders.