Table 1.
Selective human studies supporting the role of DNA methylation in post-traumatic stress disorder (PTSD).
| Reference | Candidate gene | Epigenetic changes | Sample size | Generation study carried out through |
|---|---|---|---|---|
| Koenen et al. (2011) | Slc6a4 | Lower Slc6a4 methylation levels in blood tissue and higher number of traumatic events increased risk for PTSD | 100 | F0 |
| Ressler et al. (2011) | Adcyap1r1 | Adcyap1r1 methylation levels were observed in the peripheral blood of PTSD subjects compared with control | 94 | F0 |
| Rusiecki et al. (2013) | Il8, Il16, Il18 | Increased serum Il18 methylation in combat veterans who developed PTSD, but decreased I/18 methylation levels in veterans without PTSD | 150 | F0 |
| Norrholm et al. (2013) | Comt | Higher blood level methylation of Comt are associated with impaired fear inhibition | 270 | F0 |
| Yehuda et al. (2013) | Nr3c1, Fkfbp5 | Pre psychotherapy Nr3c1 1F promoter methylation in blood tissue positively correlated with improvements in symptoms, while decreased Fkbp5 methylation occurred concomitantly with recovery from PTSD | 16 | F0 |
| Labonté et al. (2014) | Nr3c1 | Increased Nr3c1mRNA expression and decreased overall Nr3c1 1B and 1C promoter methylation levels in individuals blood with lifetime PTSD | 46 | F0 |
| Vukojevic et al. (2014) | Nr3c1 | In the peripheral blood, methylation of Nr3c1 1F promoter is linked to traumatic memories and PTSD risk in male survivors of the Rwandan genocide | 152 | F0 |
| Yehuda et al. (2014) | Nr3c1 | Nr3c1 1F promoter methylation inversely correlated with symptoms severity in the blood tissue of combat veterans with PTSD | 122 | F0 |
| Yehuda et al. (2014) | Nr3c1 | Offspring with paternal PTSD showed higher Nr3c1 1F promoter methylation in the blood tissue if maternal PTSD was not present. Offspring with maternal and paternal PTSD showed lower methylation | 95 | F0, F1(Intergeneration) |
| Perroud et al. (2014) | Nr3c1, Nr3c2 | Higher plasma levels methylation at promoter 1F for Nr3c1 in female survivors of genocide and their offspring compared to controls, but no differences observed in Nr3c2 methylation | 25 | F0, F1(Intergeneration) |
| Yehuda et al. (2016) | Fkbp5 | Holocaust survivors showed increased methylation of the promotor region for Fkbp5, while their offspring showed the opposite in their blood tissue | 71 | F0, F1(Intergeneration) |
| Kertes et al. (2017) | Bdnf | Maternal experiences of war trauma were associated with higher Bdnf methylation in umbilical cord blood, placental tissue, and lower methylation in maternal venous blood. | 24 | F0, F1(Intergeneration) |
| Serpeloni et al. (2017) | Barx1, Cftr, Corin, Smyd3 | Grandmaternal exposure to CDV during pregnancy was significantly associated with decreased methylation in Corin, Smyd3, and Barx1, and increased methylation of Cftr in grandchildren’s saliva samples | 121 | F0, F1, F2, F3 (Intergeneration) |
| Kim et al. (2017) | Bdnf | Subjects with PTSD showed a higher methylation Bdnf promoter I region in their blood tissue compared with those without PTSD | 248 | F0 |
| Voisey et al. (2019) | Bdnf | Decreased methylation at three Bdnf sites were observed in combat exposed PTSD veterans blood compared with control. | 96 | F0 |
Abbreviations: adenylate cyclase-activating polypeptide Type I receptor gene (Adcyap1r1), amplification of inter-methylated sites (Aims), BARX homeobox 1 (Barx1), brain-derived neurotrophic factor (Bdnf), catechol-O-methyltransferase gene (Comt), community and domestic violence (CDV), corin, serine peptidase genes (Corin), cystic fibrosis transmembrane conductance regulator (Cftr), FK506 binding protein 5 (Fkbp), nuclear receptor subfamily 3 group C member 1 gene (Nr3c1, glucocorticoid receptor gene), insulin like growth factor 2 (Igf2), interleukin like chemokines (Il8, Il16, Il18), nuclear receptor subfamily 3 group C member 2 gene (Nr3c2, mineralcorticoid receptor gene), SET and MYND domain containing 3 (Smyd3), solute carrier family 6 member 4 (Slc6a4).