Опубликована: Окт. 16, 2024

Most epigenetic research on post-traumatic stress disorder (PTSD) has primarily focused DNA methylation (5mC) in peripheral tissues, particularly at CpG sites. hydroxymethylation (5hmC) been found to be highly enriched the mammalian brain, while 5mC non-CpG sites shows high enrichment neurons. However, little is known about their role PTSD. Here, we characterize genome-wide differential and 5hmC both postmortem orbitofrontal neurons from PTSD cases controls. Utilizing reduced-representation oxidative bisulfite sequencing, that significant (GWS) CpGs were hyper-5mC/5hmC, whereas GWS non-CpGs hypo-5mC/5hmC. Compared with 5mC, show a more sensitive mark PTSD, higher number of stronger significance pathways. Integrating other -omics data highlighted developmental processes as convergent pathways revealed overlap our findings 50 previously reported PTSD-associated genes, including potential therapeutic targets such CRHR1 DRD4. This study underscores importance evaluating human brain multi-omics integration provides insights into target genes for future interventions Graphical abstract The conducted comprehensive analysis modifications 25 13 healthy It was observed patients exhibit greater compared Specifically, individuals tend hyper-5mC/5hmC sites, within islands promoter regions, hypo-5mC/5hmC especially intragenic regions. Functional indicated distinct yet interconnected roles marks regulate cell-cell adhesion processes, are involved embryonic morphogenesis cell fate commitment. By integrating published central tissues through approaches, several biological mechanisms prioritized, HPA axis regulation, immune responses. Based consistent hypothesize if changes occur during early stages, they may increase risk developing following trauma exposure. Conversely, these adulthood, influence neuronal apoptosis survival mechanisms.

Язык: Английский