Circulating MicroRNAs as Biomarkers in Post-Traumatic Stress Disorder and Related Psychiatric Disorders: Epigenetic Insights and Therapeutic Potential

Abstract:: Post-Traumatic Stress Disorder (PTSD)—affecting approximately 5–10% of the gen-eral population and up to 15% in trauma-exposed groups—is a debilitating mental health condi-tion triggered by life-threatening events, often causing extreme fear or helplessness. Circulating microRNAs (miRNAs), non-coding RNAs in body fluids, are emerging as non-invasive bi-omarkers for central nervous system (CNS) disorders due to their role in epigenetic regulation of gene expression. Over the past two decades, miRNA dysregulation has been implicated in psy-chiatric disorders, including PTSD, Major Depressive Disorder (MDD), Bipolar Disorder (BD), and schizophrenia (SZ), with shared features like cognitive impairment. This review showcases recent advances in miRNA dysregulation across these disorders, highlighting their potential as diagnostic tools and therapeutic targets. This review explores miRNA-mediated epigenetic mech-anisms, including transgenerational effects and glucocorticoid signaling, as novel avenues for biomarker development and therapeutic intervention in PTSD and related disorders. By integrat-ing molecular, clinical, and translational perspectives, we evaluate miRNAs’ roles in PTSD path-ogenesis, their ability to cross the blood-brain barrier, and their modulation of inflammatory and neurotrophic pathways. miRNA-based therapeutics, including miRNA mimics, anti-miRs, and exosome-mediated delivery systems, are emerging as promising interventions for restoring neu-roplasticity, normalizing glucocorticoid signaling, and reducing neuroinflammation in these dis-orders. Despite their promise, challenges such as standardized detection methods and variable expression across body fluids persist. This review underscores the potential of circulating miR-NAs in precision psychiatry, advocating for larger cohort studies and improved profiling to en-hance clinical applicability.