Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.

Meditation-based therapies such as mindfulness-based stress reduction and Transcendental Meditation can reduce PTSD symptoms in veterans. In 72 veterans with PTSD, those with the 5HTTLPR LALA high expression genotype of the serotonin transporter gene who had experienced early life trauma showed greater symptom improvement. Additionally, changes in DNA methylation at nine specific sites in the FKBP5 gene from before to after treatment were linked to greater symptom improvement, with an odds ratio of 2.8. These findings suggest that genetic and epigenetic markers in the SLC6A4 and FKBP5 genes may be important for understanding treatment mechanisms and predicting symptom improvement.

Study at a glance

Abstract

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM). The PTSD Checklist was administered to assess symptoms at baseline and after 9 weeks of meditation intervention. We examined the SLC6A4 promoter (5HTTLPR_L/S insertion/deletion + rs25531_A/G) polymorphisms according to previously defined gene expression groups, and the FKBP5 variant rs1360780 previously associated with PTSD disease risk. Methylation for CpG sites of SLC6A4 (28 sites) and FKBP5 (45 sites) genes was quantified in DNA samples collected before and after treatment. The 5HTTLPR LALA high expression genotype was associated with greater symptom improvement in participants exposed to early life trauma (p = 0.015). Separately, pre to post-treatment change of DNA methylation in a group of nine FKBP5 CpG sites was associated with greater symptom improvement (OR = 2.8, 95% CI 1.1-7.1, p = 0.027). These findings build on a wealth of existing knowledge regarding epigenetic and genetic relationships with PTSD disease risk to highlight the potential importance of SLC6A4 and FKBP5 for treatment mechanisms and as biomarkers of symptom improvement.