Successful Treatment of Post-Traumatic Stress Disorder Reverses DNA Methylation
Post by Stephanie Williams
What's the science?
Some individuals with post-traumatic stress disorder (PTSD) experience an extinction of their symptoms either spontaneously or following psychotherapy treatment. Many individuals, however, continue to experience symptoms even after treatment, demonstrating that treatment response varies among individuals with PTSD. We know that the development of PTSD is associated with changes in the regulation of gene expression, also known as epigenetic changes, such as the addition of a methyl group to DNA (i.e. methylation), which can change the expression of some genes. Less is known about the epigenetic changes that follow the successful treatment of PTSD. Identifying specific molecular changes associated with successful treatment of symptoms could advance our understanding of the biological process underlying recovery, and explain why some individuals do not respond to treatment. This week in Molecular Psychiatry, Vinkers and colleagues used data collected from trauma-exposed soldiers to identify specific changes in DNA methylation linked to recovery from PTSD symptoms following treatment.
How did they do it?
First, the authors confirmed that the PTSD psychotherapy treatment could effectively reduce PTSD symptoms for some individuals, as indexed by decreases in scores on a standard psychological interview, called CAPS. The authors then performed longitudinal genome-wide DNA methylation analyses in two separate cohorts to address questions about epigenetic-related treatment changes. To investigate recovery-related epigenetic changes, the authors analyzed DNA extracted from the blood of 44 male war veteran patients with PTSD and 23 trauma-exposed male war veterans without PTSD (controls). The data were collected from the 2010-2013 longitudinal study BETTER and included blood samples taken before and after the individuals were treated for PTSD. The authors analyzed the methylation profile of both samples for patients who did (N=21) and did not (N=23) respond to treatment. The severity and diagnosis of PTSD were established via an oral interview that was administered by a clinician or researcher. The authors looked for DNA regions that were differentially methylated following symptom reduction in response to the successful treatment of PTSD. Treatment administered to patients was either both (1) eye movement desensitization and reprocessing and trauma-focused cognitive behavioral therapy, or (2) trauma-focused cognitive behavioral therapy alone. To understand whether the different treatment arms induced different molecular changes, the authors compared methylation changes induced by the two treatment types. After identifying several DNA-methylation changes in specific regions in the recovery cohort, the authors analyzed the same regions in a separate PRISMO military cohort, which included blood samples before deployment, and 1 and 5 months post-deployment to Afghanistan. Using the two cohorts, the authors looked for regions that showed opposite patterns of methylation during symptom development and remission.
What did they find?
The authors identified twelve differentially methylated regions that were significantly associated with a reduction in PTSD symptoms after treatment in the BETTER cohort. When the authors analyzed the methylation status of the same regions in the PRISMO cohort, they found that only one of the twelve identified regions was significantly decreased in proportion to increased PTSD symptoms during the development of the disorder. The region, called ZFP57, showed an increase in methylation following symptom extinction and a reduction in methylation following the development of PTSD symptoms. The authors interpret this evidence as suggesting that ZFP57 methylation is involved in deployment-related PTSD. Next, that authors compared the two different treatments on methylation of ZFP57 and found that the eye movement desensitization treatment, induced slightly greater methylation than trauma-focused cognitive behavioral therapy. Both of the methylation changes induced by the treatments were disproportionately larger (greater methylation than would have been expected for the reduction in symptom scores) than expected, given the corresponding reduction in PTSD symptoms. The authors interpreted this finding as indicating that the treatment-induced methylation changes were directly influenced by the treatment and not due to symptom remission alone.
What's the impact?
The authors have identified specific methylation changes that associate with symptom development and remission. They show that treatments such as cognitive-behavioral therapy and eye movement desensitization can directly affect the biology of patients on a molecular level. Their identification of a specific genomic region, ZFP57, associated with successful treatment of PTSD symptoms will allow future research to parse apart how treatments can exert successful molecular changes to improve future treatment outcomes.
Vinkers et al. Successful treatment of post-traumatic stress disorder reverses DNA methylation marks. Nature Molecular Psychiatry (2019). Access the original scientific publication here.