Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD Article Swipe
Candace R. Lewis
,
Joseph Tafur
,
Sophie Spencer
,
Joseph M. Green
,
Charlotte Harrison
,
Benjamin Kelmendi
,
David M. Rabin
,
Rachel Yehuda
,
Berra Yazar‐Klosinski
,
Baruch Rael Cahn
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fpsyt.2023.959590
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3389/fpsyt.2023.959590
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fpsyt.2023.959590
- OA Status
- gold
- Cited By
- 23
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4319322412
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4319322412Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fpsyt.2023.959590Digital Object Identifier
- Title
-
Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSDWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-02-06Full publication date if available
- Authors
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Candace R. Lewis, Joseph Tafur, Sophie Spencer, Joseph M. Green, Charlotte Harrison, Benjamin Kelmendi, David M. Rabin, Rachel Yehuda, Berra Yazar‐Klosinski, Baruch Rael CahnList of authors in order
- Landing page
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https://doi.org/10.3389/fpsyt.2023.959590Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.3389/fpsyt.2023.959590Direct OA link when available
- Concepts
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Glucocorticoid receptor, Glucocorticoid, DNA methylation, Medicine, MDMA, Pharmacology, Psychology, Gene, Internal medicine, Biology, Genetics, Gene expressionTop concepts (fields/topics) attached by OpenAlex
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23Total citation count in OpenAlex
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2025: 8, 2024: 9, 2023: 6Per-year citation counts (last 5 years)
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53Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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