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

AbstractDNA 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 out-come. However, most did not control for changes in cell composition from pre- to post-therapy. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD) using targeted deep bisulfite sequencing (DBS). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD and three patients with anorexia nervosa (AN) before and after intervention. 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). Furthermore, 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. 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 AN.Author SummaryMany mental health problems have developmental origin, and epigenetic mechanisms have been proposed to explain the link between stressful or adverse experiences and subsequent health outcomes. More recently, studies have begun to examine whether psychological therapies might influence or even reverse supposedly acquired DNA methylation marks. Correlations between response to therapy and DNA methylation changes in peripheral tissue have been reported; however, these results might be confounded by differences in cell composition between time points and not reflect true DNA methylation changes. Here, we attempted to replicate previous reported results in a homogenous cell population (monocytes) and further to identify novel intervention-responsive regions in the whole genome in patients with post-traumatic stress disorder (PTSD) and anorexia nervosa (AN).Our results showed that the improvement in symptomatology in PTSD and AN patients was not reflected in changes in DNA methylation in monocytes, neither in the previously studied candidate genes nor in the regions identified by whole-genome bisulfite sequencing. This study provides evidence against DNA methylation changes in peripheral tissue following therapy, and we suggest that previous findings are most likely explained by differences in cell composition.