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©The Author(s) 2022.
World J Psychiatry. Sep 19, 2022; 12(9): 1150-1168
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1150
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1150
Table 1 DNA methylation studies on depressed subjects, also associated with suicidality and life adversities
Gene (region) | Alteration | Subjects and collected tissue | Ref. |
NR3C1 1-F and FKBP5 intron 7 promoter | ↑ DNA methylation at NR3C1 1-F, without significant differences at any of the measured individual CpG site in depressed patients. Association in salivary cortisol level and DNA methylation. ↑ DNA methylation in NR3C1 1-F at CpG 38 site in depressed patients, with early life adversity. No differences in FKBP5 intron 7 promoter | 33 depressed patients (24 females, 9 males), 34 controls (21 females, 13 males). Whole blood and saliva | Farrell et al[67], 2018 |
MAOA and NR3C1 exon 1-F | ↓ DNA methylation at MAOA’s first exon/intron junction; significantly ↓ at CpG 8 site from the intron region. ↑ DNA methylation at NR3C1 1-F’s promoter and exon in individuals experienced early parental death; significant ↑ at CpG 35 and 10.11 (sites close to NGFI-A binding site) | 82 (for MAOA gene) and 93 (for NR3C1 1-F gene) depressed females, victims of early-life adversity and 92 or 83 controls. Saliva | Melas et al[35], 2013 |
BDNF, NR3C1, and FKBP5 | Significant alteration in DNA methylation at 9 sites in BDNF gene body, at 6 sites in NR3C1 promoter region, and at 4 sites in FKBP5 gene body, 3’UTR and promoter | 94 maltreated and 96 non-traumatized children. Saliva | Weder et al[68], 2014 |
BDNF exon I | ↓ DNA methylation; differences at loci 87, 88 and 92–94, located within the CpG island region on the promoter of the exon I | 360 depressed patients (32 females, 328 males). Saliva | Song et al[69], 2014 |
BDNF promoter between –694 and –577 relative to the transcriptional start site (12 CpG sites). SLC6A4 promoter adjacent to exon 1a between –479 and –350 relative to the transcriptional start site (10 CpG sites) | Depressed mood in 2nd trimester associated with ↓ DNA methylation at maternal SLC6A4 promoter methylation status. ↓ DNA methylation at SLC6A4 promoter in infants, from mothers with higher depressed mood during 2nd trimester. No difference in BDNF gene | 82 female and male infants exposed to prenatal maternal stress–33 mothers treated with SRI and 49 mothers not treated with SRI. Blood | Devlin et al[70], 2010 |
NR3C1 exon 1-F and BDNF promoter IV | ↑ DNA methylation within NR3C1 1-F gene (male infants). ↓ DNA methylation within BDNF promoter IV region (female and male infants) | 20 female and male infants exposed to prenatal maternal stress and 37 controls. Buccal tissue | Braithwaite et al[71], 2015 |
NR3C1 exon 1-F | Depressed mood in 2nd trimester associated with ↑ DNA methylation of CpG 2 site (relative to translational start site) at NR3C1 exon 1-F in infants. Depressed mood in 3d trimester associated with ↑ DNA methylation of CpG 2 and CpG 3 site (relative to translational start site) at NR3C1 exon 1-F in infants | 46 depressed females (33 treated with SRI and 13 not medicated), 36 controls, and their infants. Blood | Oberlander et al[72], 2008 |
BDNF, NR3C1, CRHBP, CRHR1, FKBP5 promoter | Hypermethylated BDNF, NR3C1, CRHBP and FKBP5 promoter. mRNA down regulation of BDNF, NR3C1, FKBP5 and CRHBP in MDD-suicidal ideation group | 15 females and 9 males with MDD (14 with and 10 without suicidal ideation) and 20 controls (14 females and 6 males). PBMC | Roy et al[73], 2017 |
BDNF exon I promoter | ↑ percentage of methylated reference values | 207 female and male MDD patients and 278 controls. PBMC | Carlberg et al[58], 2014 |
BDNF exon I promoter | ↑ at CpG 1, CpG 3 and CpG 5 site, ↓ BDNF serum level | 49 female and male MDD patients and 57 controls. Blood | Schröter et al[74], 2020 |
BDNF exon I and IV promoter | ↑ methylation at CpG site 3 of promoter IV | 251 female and male MDD patients aged 65 > and 773 controls. Buccal tissue | Januar et al[75], 2015 |
BDNF exon IX | Changes in DNA methylation; ↑ at CpG site 217, ↓ at CpG site 327, and 362. ↓ BDNF level and mRNA levels | 51 MDD patients (35 females and 16 males) and 62 controls (39 females and 23 males). Venous blood | Hsieh et al[60], 2019 |
BDNF upstream of exon I and IV | Changes in DNA methylation within CpG exon I promoter | 20 MDD patients (12 females and 8 males) and 18 controls (8 females and 10 males). Blood | Fuchikami et al[76], 2011 |
MYO16 and IDE | ↑ 5hmc in one CpG position of MYO16 and two CpG positions of IDE in the PFC. ↑ gene expression of MYO16. ↓ gene expression of IDE | 19 depressed male suicide victims and 19 controls. Brain tissue (PFC; inferior frontal gyrus) | Gross et al[77], 2017 |
GABAA receptor α1 subunit promoter | ↑ DNA methylation of the CpG 2 and CpG 4 site (500 bp from transcriptional start site). ↑ DNMT-3B expression in FPC. ↓ expression of DNMT1 mRNA and ↑ expression of DNMT3b mRNA in FPC. ↓ expression of DNMT3b and DNMT1 mRNA in AMG | 10 male suicide victims and 10 controls. Brain tissue (FPC, AMG) | Poulter et al[78], 2008 |
SLC6A4 promoter | ↑ mean methylation level | 28 MDD patients (20 females and 8 males) and 29 controls (21 females and 8 males). Blood | Iga et al[79], 2016 |
NR3C1 exon 1 promoter | ↑ methylation at CpG 30 and 32 site. ↓ expression of total NR3C1 mRNA and NR3C1-1F mRNA in suicide victims without childhood abuse and control group | 12 suicide victims with traumatic childhood experience, 12 suicide victims without traumatic childhood experience, and 12 controls. Brain tissue (HPC) | McGowan et al[80], 2009 |
- Citation: Šalamon Arčan I, Kouter K, Videtič Paska A. Depressive disorder and antidepressants from an epigenetic point of view. World J Psychiatry 2022; 12(9): 1150-1168
- URL: https://www.wjgnet.com/2220-3206/full/v12/i9/1150.htm
- DOI: https://dx.doi.org/10.5498/wjp.v12.i9.1150