PMID- 36815187
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230325
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 14
DP  - 2023
TI  - Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) 
      is associated with MDMA-assisted therapy treatment response for severe PTSD.
PG  - 959590
LID - 10.3389/fpsyt.2023.959590 [doi]
LID - 959590
AB  - BACKGROUND: Previous research has demonstrated that epigenetic changes in 
      specific hypothalamic-pituitary-adrenal (HPA) genes may predict successful 
      psychotherapy in post-traumatic stress disorder (PTSD). A recent Phase 3 clinical 
      trial reported high efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted 
      therapy for treating patients with severe PTSD compared to a therapy with placebo 
      group (NCT03537014). This raises important questions regarding potential 
      mechanisms of MDMA-assisted therapy. In the present study, we examined epigenetic 
      changes in three key HPA axis genes before and after MDMA and placebo with 
      therapy. As a pilot sub-study to the parent clinical trial, we assessed potential 
      HPA epigenetic predictors for treatment response with genomic DNA derived from 
      saliva (MDMA, n = 16; placebo, n = 7). Methylation levels at all 259 CpG sites 
      annotated to three HPA genes (CRHR1, FKBP5, and NR3C1) were assessed in relation 
      to treatment response as measured by the Clinician-Administered PTSD Scale 
      (CAPS-5; Total Severity Score). Second, group (MDMA vs. placebo) differences in 
      methylation change were assessed for sites that predicted treatment response. 
      RESULTS: Methylation change across groups significantly predicted symptom 
      reduction on 37 of 259 CpG sites tested, with two sites surviving false discovery 
      rate (FDR) correction. Further, the MDMA-treatment group showed more methylation 
      change compared to placebo on one site of the NR3C1 gene. CONCLUSION: The 
      findings of this study suggest that therapy-related PTSD symptom improvements may 
      be related to DNA methylation changes in HPA genes and such changes may be 
      greater in those receiving MDMA-assisted therapy. These findings can be used to 
      generate hypothesis driven analyses for future studies with larger cohorts.
CI  - Copyright (c) 2023 Lewis, Tafur, Spencer, Green, Harrison, Kelmendi, Rabin, Yehuda, 
      Yazar-Klosinski and Cahn.
FAU - Lewis, Candace R
AU  - Lewis CR
AD  - School of Life Sciences, Arizona State University, Tempe, AZ, United States.
AD  - Neurogenomics Division, Translational Genomics Research Institute (TGen), 
      Phoenix, AZ, United States.
FAU - Tafur, Joseph
AU  - Tafur J
AD  - Modern Spirit, Phoenix, AZ, United States.
FAU - Spencer, Sophie
AU  - Spencer S
AD  - School of Life Sciences, Arizona State University, Tempe, AZ, United States.
FAU - Green, Joseph M
AU  - Green JM
AD  - School of Life Sciences, Arizona State University, Tempe, AZ, United States.
FAU - Harrison, Charlotte
AU  - Harrison C
AD  - MAPS Public Benefit Corporation, San Jose, CA, United States.
FAU - Kelmendi, Benjamin
AU  - Kelmendi B
AD  - Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, 
      United States.
FAU - Rabin, David M
AU  - Rabin DM
AD  - The Board of Medicine, Pittsburgh, PA, United States.
FAU - Yehuda, Rachel
AU  - Yehuda R
AD  - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 
      United States.
AD  - Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY, United 
      States.
FAU - Yazar-Klosinski, Berra
AU  - Yazar-Klosinski B
AD  - MAPS Public Benefit Corporation, San Jose, CA, United States.
FAU - Cahn, Baruch Rael
AU  - Cahn BR
AD  - Department of Psychiatry and Behavioral Sciences, University of Southern 
      California, Los Angeles, CA, United States.
AD  - Brain and Creativity Institute, University of Southern California, Los Angeles, 
      CA, United States.
LA  - eng
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20230206
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC9939628
OTO - NOTNLM
OT  - DNA methylation
OT  - HPA
OT  - MDMA
OT  - MDMA-assisted therapy
OT  - NR3C1
OT  - PTSD
OT  - epigenetics
OT  - glucocorticoid receptor
COIS- BY-K and CH received payment for full-time employment from the MAPS or the MAPS 
      Public Benefit Corporation throughout their work on the parent trial. JT is the 
      Executive Director of Modern Spirit, the non-profit organization that funded this 
      study. BC is on the Board of Directors for Modern Spirit. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2023/02/24 06:00
MHDA- 2023/02/24 06:01
PMCR- 2023/02/06
CRDT- 2023/02/23 02:16
PHST- 2022/06/01 00:00 [received]
PHST- 2023/01/17 00:00 [accepted]
PHST- 2023/02/23 02:16 [entrez]
PHST- 2023/02/24 06:00 [pubmed]
PHST- 2023/02/24 06:01 [medline]
PHST- 2023/02/06 00:00 [pmc-release]
AID - 10.3389/fpsyt.2023.959590 [doi]
PST - epublish
SO  - Front Psychiatry. 2023 Feb 6;14:959590. doi: 10.3389/fpsyt.2023.959590. 
      eCollection 2023.