Dataset Information

DNA methylation levels are associated with CRF₁ receptor antagonist treatment outcome in women with post-traumatic stress disorder.

ABSTRACT:

Background

We have previously evaluated the efficacy of the CRF₁ receptor antagonist GSK561679 in female PTSD patients. While GSK561679 was not superior to placebo overall, it was associated with a significantly stronger symptom reduction in a subset of patients with probable CRF system hyperactivity, i.e., patients with child abuse and CRHR1 SNP rs110402 GG carriers. Here, we test whether blood-based DNA methylation levels within CRHR1 and other PTSD-relevant genes would be associated with treatment outcome, either overall or in the high CRF activity subgroup.

Results

Therefore, we measured CRHR1 genotypes as well as baseline and post-treatment DNA methylation from the peripheral blood in the same cohort of PTSD-diagnosed women treated with GSK561679 (N = 43) or placebo (N = 45). In the same patients, we assessed DNA methylation at the PTSD-relevant genes NR3C1 and FKBP5, shown to predict or associate with PTSD treatment outcome after psychotherapy. We observed significant differences in CRHR1 methylation after GSK561679 treatment in the subgroup of patients with high CRF activity. Furthermore, NR3C1 baseline methylation significantly interacted with child abuse to predict PTSD symptom change following GSK561679 treatment.

Conclusions

Our results support a possible role of CRHR1 methylation levels as an epigenetic marker to track response to CRF₁ antagonist treatment in biologically relevant subgroups. Moreover, pre-treatment NR3C1 methylation levels may serve as a potential marker to predict PTSD treatment outcome, independent of the type of therapy. However, to establish clinical relevance of these markers, our findings require replication and validation in larger studies.

Trial registration

NCT01018992 . Registered 6 November 2009.

SUBMITTER: Pape JC

PROVIDER: S-EPMC6215613 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA methylation levels are associated with CRF<sub>1</sub> receptor antagonist treatment outcome in women with post-traumatic stress disorder.

Pape Julius C JC Carrillo-Roa Tania T Rothbaum Barbara O BO Nemeroff Charles B CB Czamara Darina D Zannas Anthony S AS Iosifescu Dan D Mathew Sanjay J SJ Neylan Thomas C TC Mayberg Helen S HS Dunlop Boadie W BW Binder Elisabeth B EB

Clinical epigenetics 20181103 1

<h4>Background</h4>We have previously evaluated the efficacy of the CRF<sub>1</sub> receptor antagonist GSK561679 in female PTSD patients. While GSK561679 was not superior to placebo overall, it was associated with a significantly stronger symptom reduction in a subset of patients with probable CRF system hyperactivity, i.e., patients with child abuse and CRHR1 SNP rs110402 GG carriers. Here, we test whether blood-based DNA methylation levels within CRHR1 and other PTSD-relevant genes would be a ...[more]

PMID: 30390684

Similar Datasets

Project description:BackgroundKidney transplantation (KT) is a life-saving therapy for kidney failure. However, KT recipients can suffer from debilitating depression, post-traumatic stress disorder (PTSD), and suicide. In contrast to PTSD, post-traumatic growth (PTG) is a positive psychologic change in response to a challenging situation. PTG has been studied in other chronic diseases, but less is known about its role in the setting of KT. We sought to elucidate the prevalence, predictors, and the effect of PTSD and PTG on post-KT outcomes. We also considered the roles of benefit finding and resilience.MethodsIn a literature review, we identified publications that examined PTSD, PTG, benefit finding, and/or resilience in KT recipients. We excluded case reports and first-person narratives. Publications meeting the specified criteria after full text review underwent data abstraction and descriptive analysis.ResultsOf the 1013 unique citations identified, 39 publications met our criteria. PTSD was the most common construct evaluated (16 publications). Resilience was studied in 11 publications, PTG in nine, and benefit finding in five. Up to 21% of adult and 42% of pediatric KT recipients may experience PTSD, which is associated with lower quality of life (QOL), impaired sleep, and other psychiatric comorbidity. PTG was associated with improved QOL, kidney function, and reduced risk of organ rejection. Although benefit finding tended to increase post KT, resilience remained stable post KT. Like PTG, resilience was associated with lower psychologic distress and increased treatment adherence and confidence in the health care team.ConclusionsPTG, resilience, and benefit finding appear to reduce the risk of PTSD, promote well-being, and reduce risk of graft failure in KT recipients. Future research to understand these relationships better will allow clinicians and researchers to develop interventions to promote PTG, resilience, and benefit finding, and potentially improve post-transplant outcomes such as adherence and reducing risk of organ rejection.

Dataset Information

DNA methylation levels are associated with CRF₁ receptor antagonist treatment outcome in women with post-traumatic stress disorder.

Background

Results

Conclusions

Trial registration

Publications

DNA methylation levels are associated with CRF<sub>1</sub> receptor antagonist treatment outcome in women with post-traumatic stress disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

DNA methylation levels are associated with CRF1 receptor antagonist treatment outcome in women with post-traumatic stress disorder.

Background

Results

Conclusions

Trial registration

Publications

DNA methylation levels are associated with CRF<sub>1</sub> receptor antagonist treatment outcome in women with post-traumatic stress disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

DNA methylation levels are associated with CRF₁ receptor antagonist treatment outcome in women with post-traumatic stress disorder.