Table 2.
A summary of epigenetic modifications in human and animal models of PTSD.
| Species/model | Gene(s) of interest | Major findings | Reference |
|---|---|---|---|
| CANDIDATE-GENE STUDIES | |||
| Human | ADCYAP1, ADCYAP1R1 | PTSD symptoms correlated with Adcyap1r1 locus in women | Ressler et al. (2011) |
| Rat – predator odor + social instability | Bdnf | ↑ Exon IV methylation in dorsal DG and CA1, ↓exon IV methylation in ventral CA3, ↓exon IV mRNA in both dorsal and ventral CA1 | Roth et al. (2011) |
| Human | SLC6A4 | Controlling for genotype, SLC6A4 methylation modified the effect of PTEs on PTSD: ↓ SLC6A4 promoter methylation associated with ↑PTSD risk; ↑SLC6A4 promoter methylation was protective against PTSD | Koenen et al. (2011) |
| Human | SLC6A3 | ↑ SLC6A3 promoter methylation associated with ↑risk of lifetime PTSD in 9R allele carriers | Chang et al. (2012) |
| Human | COMT | COMT Met/Met genotype interacted with CpG methylation in mediating impaired fear inhibition in PTSD patients | Norrholm et al. (2013) |
| Human | FKBP5 | GC exposure was associated with ↑ FKBP5 GRE demethylation and ↑FKBP5 expression in carriers of the risk compared with the protective allele | Klengel et al. (2013) |
| GENOME-WIDE/LARGE SCALE STUDIES | |||
| Human | Genes involved in immunity, neurogenesis, the startle response, DNMT3B, DNMT3L, imprinted genes: NDN, MAGEL2, ATP10A | PTSD was associated with: (1) ↑ methylation of DNMT3B, ↓methylation of DNMT3L; (2) degulated methylation of genes involved in Prader–Willi and Angelman syndromes; (3) methylation profiles suggesting upregulation of immune-related genes and downregulation of genes involved in neurogenesis and the startle response | Uddin et al. (2010) |
| Rat – predator odor | Dlgap2, Dll3, Pkcη, Rps6kb2 | Of the four differentially methylated genes identified, Dlgap2 was associated with a change in mRNA expression. ↓ intragenic methylation associated with ↓hippocampal mRNA expression | Chertkow-Deutsher et al. (2010) |
| Human | TPR, CLEC9A, APC5, ANXA2, TLR8, BDNF, CXCL1, immune-related genes | PTSD associated with: (1) ↓ methylation of TPR and ANXA2 and ↑methylation of CLEC9A, APC5, TLR8 in PTSD; (2) ↑methylation of BDNF and CXCL1; (3) 19 of 54 of the differentially methylated immune-related genes examined in Uddin et al. (2010) | Smith et al. (2011) |
| OTHER | |||
| Human | 33 loci previously associated with PTSD | Only MAN2C1 showed evidence of interaction with PTE no. in PTSD risk: ↑ MAN2C1 methylation interacted with ↑no. of PTEs to ↑PTSD risk | Uddin et al. (2011) |
| Human | Repetitive elements: LINE-1, Alu | In US military service members recently deployed to Afghanistan or Iraq: LINE-1 was hypomethylated in PTSD cases vs. control post-deployment. Alu was hypermethylated in PTSD cases vs. control pre-deployment | Rusiecki et al. (2012) |
PTE, potentially traumatic event; TLS, total life stress; ADCYAP1, adenylate cyclase-activating polypeptide 1 (pituitary); ADCYAP1R1, adenylate cyclase-activating polypeptide 1 (pituitary) receptor type I; Bdnf, brain-derived neurotrophic factor; SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin), member; SLC6A3, solute carrier family 6 (neurotransmitter transporter, dopamine), member; COMT, catechol-O-methyltransferase; FKBP5, FK506 binding protein 5; DNMT3B, DNA methyltransferase-3B; DNMT3L, DNA methyltransferase-3L; NDN, necdin, melanoma antigen (MAGE) family member; MAGEL2, MAGE-like 2; ATP10A, ATPase, class V, type 10A; Dlgap2, disks large-associated protein 2; Dll3, delta-like 3; Pkcη, protein kinase C η; Rps6kb2, ribosomal protein S6 kinase polypeptide 2; TPR, translocated promoter region; CLEC9A, C-type lectin domain family 9, member A; APC5, acid phosphatase 5, tartrate resistant; ANXA2, annexin A2; TLR8, toll-like receptor 8; CXCL1, chemokine (C-X-C motif) ligand 1; MAN2C1, mannosidase, alpha, class 2c, member 1.