Epigenetic Contributors to PTSD: a Comprehensive Review

Abstract

Background: Post-traumatic stress disorder (PTSD) is a complex condition triggered by traumatic events. The molecular mechanisms underlying PTSD are not fully understood, but epigenetic modifications, particularly DNA methylation, may play a key role. The objective of this review was to identify the most significant epigenetic markers associated with PTSD.

Materials and methods: Our search yielded 325 articles, of which 19 met our inclusion criteria for detailed analysis: published between 2018 and 2024, original research, containing molecular-genetic and statistical data, reporting diagnostic verification methods, PTSD as a primary condition, and a sample of at least 40 patients Results: the strongest correlation was found between PTSD and methylation changes in cg17057218, cg22324981, cg04755409 of BDNF, cg05656210, cg12169700, cg20756026 of MAD1L1, HLA-DPA1, HLA-DPB1 (chr6: 33047185 - 33049505) and SPATC1L (chr21: 47604052 - 47605174). The most works on associations of genetic clock with PTSD found significantly increased GrimAge acceleration in patients with PTSD.

Conclusions: Epigenetic modifications, particularly DNA methylation, play a significant role in PTSD pathophysiology. While specific gene methylation changes are associated with PTSD, the link between PTSD and epigenetic aging remains unclear. Variability across studies suggests that trauma type, duration, and genetic factors may influence these epigenetic processes. Further research is essential to fully understand these relationships.

Keywords: epigenetics – GrimAge – CpG - methylation - post-traumatic stress disorder.