Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.
Jeffrey R Bishop, Adam M Lee, Lauren J Mills, Paul Thuras, Seenae Eum, Doris Clancy, Christopher R Erbes, Melissa A Polusny, Gregory J Lamberty, Kelvin O Lim
Frontiers in Psychiatry 2018 DOI: 10.3389/fpsyt.2018.00418 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort (nested in a clinical trial) Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Veterans with PTSD who were responders or non-responders to MBSR |
| Intervention | Mindfulness Based Stress Reduction (MBSR) |
| Topics | Meditation PTSD |
| Keywords | Dna methylation Fkbp5 Slc6a4 Epigenetics Treatment response |
| Key findings | Responders to MBSR showed decreased FKBP5 intron 7 bin 2 methylation from before to after treatment, while non-responders showed increased methylation, with a significant time x responder group interaction. |
Abstract
Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic treatment for veterans with PTSD. Extensive work has identified epigenetic factors related to PTSD disease risk and pathophysiology, but how these factors influence treatment response is unclear. Serotonin signaling and hypothalamic-pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are molecular pathways targeted by PTSD treatments. To identify potential biomarkers for treatment response, we utilized genomic DNA isolated from peripheral blood samples from veterans with PTSD who were responders (n = 11) or non-responders (n = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements suggested to regulate this gene. Selected subjects were matched across MBSR responder status by baseline symptoms, age, sex, current smoking status, and current antidepressant use. Percent methylation was compared between responders and non-responders at baseline (pre-MBSR treatment). Additionally, percent change in methylation from baseline to post-treatment was compared between responders and non-responders. There was a significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2 [F (1, 19) = 7.492, p = 0.013] whereby responders had a decrease in methylation and non-responders had an increase in methylation from before to after treatment in this region. Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 [F (1, 19) = 5.551, p = 0.029] which resides in a known glucocorticoid response element (GRE). Decreases in FKBP5 methylation after treatment in responders as compared to increases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. These preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of response to meditation treatment in PTSD and require validation in larger cohorts.
Comparable studies
Other non-randomized and open-label trials on PTSD, most cited first.
Citations in the library
Cited by 21
- Ceremonial Ayahuasca in Amazonian Retreats—Mental Health and Epigenetic Outcomes From a Six-Month Naturalistic Study Frontiers in Psychiatry June 9, 2021
- Biological mechanism study of meditation and its application in mental disorders General Psychiatry July 13, 2020
- The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study BMC Complementary Medicine and Therapies April 15, 2021
- Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD Frontiers in Psychiatry February 6, 2023
- Epigenetic Echoes: Bridging Nature, Nurture, and Healing Across Generations. International Journal of Molecular Sciences March 27, 2025
and 16 more in the library
Cites 5
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- Activation of the anterior prefrontal cortex and serotonergic system is associated with improvements in mood and EEG changes induced by Zen meditation practice in novices. International Journal of Psychophysiology May 1, 2011