Dataset Information

Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder.

ABSTRACT: BACKGROUND:Epigenetic differences exist between trauma-exposed individuals with and without post-traumatic stress disorder (PTSD). It is unclear whether these epigenetic differences pre-exist, or arise following, trauma and PTSD onset. METHOD:In pre- and post-trauma samples from a subset of Detroit Neighborhood Health Study participants, DNA methylation (DNAm) was measured at DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B and DNMT3L. Pre-trauma DNAm differences and changes in DNAm from pre- to post-trauma were assessed between and within PTSD cases (n = 30) and age-, gender- and trauma exposure-matched controls (n = 30). Pre-trauma DNAm was tested for association with post-trauma symptom severity (PTSS) change. Potential functional consequences of DNAm differences were explored via bioinformatic search for putative transcription factor binding sites (TFBS). RESULTS:DNMT1 DNAm increased following trauma in PTSD cases (p = 0.001), but not controls (p = 0.067). DNMT3A and DNMT3B DNAm increased following trauma in both cases (DNMT3A: p = 0.009; DNMT3B: p < 0.001) and controls (DNMT3A: p = 0.002; DNMT3B: p < 0.001). In cases only, pre-trauma DNAm was lower at a DNMT3B CpG site that overlaps with a TFBS involved in epigenetic regulation (p = 0.001); lower pre-trauma DNMT3B DNAm at this site was predictive of worsening of PTSS post-trauma (p = 0.034). Some effects were attenuated following correction for multiple hypothesis testing. CONCLUSIONS:DNAm among trauma-exposed individuals shows both longitudinal changes and pre-existing epigenetic states that differentiate individuals who are resilient versus susceptible to PTSD. These distinctive DNAm differences within DNMT loci may contribute to genome-wide epigenetic profiles of PTSD.

SUBMITTER: Sipahi L

PROVIDER: S-EPMC4530981 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder.

Sipahi L L Wildman D E DE Aiello A E AE Koenen K C KC Koenen K C KC Galea S S Abbas A A Uddin M M

Psychological medicine 20140425 15

<h4>Background</h4>Epigenetic differences exist between trauma-exposed individuals with and without post-traumatic stress disorder (PTSD). It is unclear whether these epigenetic differences pre-exist, or arise following, trauma and PTSD onset.<h4>Method</h4>In pre- and post-trauma samples from a subset of Detroit Neighborhood Health Study participants, DNA methylation (DNAm) was measured at DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B and DNMT3L. Pre-trauma DNAm differences and changes in DNA ...[more]

PMID: 25065861

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Project description:The biological underpinnings of post-traumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biological mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n=100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assay CpG sites from over 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD-affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biological marker of immune response to infection, cytomegalovirus—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. These results provide the first report of peripheral epigenomic and CMV profiles associated with mental illness and suggest a new biological model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. Bisulfite conversion of whole blood-derived DNA samples was performed using the EZ-96 DNA methylation kit from Zymo Research. One microgram (μg) of each sample (including controls) was subjected to bisulfite conversion following manufacturer’s recommended protocol. 100 samples were analyzed of which 23 are PTSD affected and 77 are PTSD-unaffected. There were four technical replicates comprised of duplicate samples of two randomly selected individuals from the n=100 and duplicate samples of the control human methylated and unmethylated DNA.

Project description:BackgroundSleep disturbances are common in individuals with post traumatic stress disorder (PTSD). However, little is known about how daily variation in sleep characteristics is related to PTSD. This study examined the night-to-night and weekday versus weekend variation in sleep duration, sleep quality, trouble falling asleep, and difficulty staying asleep in individuals with and without PTSD.MethodsParticipants (N = 157; 80 with PTSD, 77 without PTSD) completed daily self-reports of their nighttime sleep characteristics for 15 consecutive days. Linear mixed models were used to examine the associations between the 7 days of the week and weekday versus weekend variation in sleep characteristics and PTSD.ResultsIndividuals with PTSD reported shorter sleep duration, lower sleep quality, more trouble falling asleep, and more difficulty staying asleep than individuals without PTSD. The pattern of change across the week and between weekdays and weekends was different between those with and without PTSD for sleep quality and trouble falling asleep. Among those with PTSD, sleep duration, sleep quality, and trouble falling asleep differed across the 7 days of the week and showed differences between weekdays and weekends. For those without PTSD, only sleep duration differed across the 7 days of the week and showed differences between weekdays and weekends. Neither group showed 7 days of the week nor weekday versus weekend differences in difficulty staying asleep.ConclusionsOn average those with PTSD had shorter sleep duration, poorer sleep quality, and greater trouble falling and staying asleep. In particular, the day of week variation in sleep quality and trouble falling asleep specifically distinguishes those with PTSD from those without PTSD. Our findings suggest that clinical care might be improved by assessments of sleep patterns and disturbances across at least a week, including weekdays and weekends. Future studies should explore the mechanisms related to the patterns of sleep disturbance among those with PTSD.

Dataset Information

Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder.

Publications

Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder.

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