No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder or anorexia nervosa

Background: DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition from pre- to post-therapy. Here, we addressed this limitation and analyzed DNA methylation patterns by targeted deep bisulfite sequencing (DBS) of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD) before and after in-patient treatment. Furthermore, in two patients with PTSD and three patients with anorexia nervosa (AN), whole-genome bisulfite sequencing (WGBS) was performed before and after intervention with the aim of identifying novel genomic regions with notable pre-to-post intervention DNA methylation changes. Results: WGBS yielded only a limited set of candidate regions with suggestive evidence of differential methylation pre- to post-therapy. These differential methylation patterns did not prove replicable when investigated in the entire cohort. Furthermore, equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Conclusions: We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with either PTSD or anorexia nervosa.