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.