Epigenetic changes in post-traumatic stress disorder: possibilities and limitations of epigenetic therapy

In recent decades, the steadily increasing pressure of extreme, life-threatening stressors worldwide has significantly contributed to a rise in the prevalence of mental and behavioral disorders. One of the most severe consequences of experiencing psychotraumatic situations is the development of post-traumatic stress disorder. Current therapeutic approaches benefit only a minority of patients and are frequently accompanied by high non-response and relapse rates. In this case, the possible reasons for the lack of therapeutic effectiveness include not only genetic but also epigenetic factors, which may determine individual characteristics of the pharmacokinetics and pharmacodynamics of the drugs used. This review outlines epigenetic mechanisms that may underlie interindividual differences in treatment resistance, risk of development, and clinical severity of post-traumatic stress disorder. It summarizes the roles of DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and the three-dimensional genome architecture in post-traumatic and stress-related disorders. Data are presented on the potential use of epigenetic modifications as biomarkers of traumatic stress and as factors responsible for the transmission to offspring of the adverse consequences of psychogenic trauma experienced by the parents. The possibilities and limitations of applying epigenetic therapy for post-traumatic stress disorder are discussed.