Table 2 Studies description table.
First author, year | N tot (ne, nc) | Age | Sex (female %) | Ethnicity (as reported in papers) | Type of depression | Severity of depression | Primary disorder | Depression scale used | Comorbidity | Controls Used | Sample | Methylation technique | Single-CpG resolution option? | CpG Data Type Used for Effect Computation | Number of CpGs (/74 CpG in the CpG island) | Genomic location | GRCh38/hg38 conversion UCSC Liftover - 30 23_ _ _ _ (for ref. 799 bp CpG island: 5 370 – 6 168) | Study Effect Sizes | Expression tested? |
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Meta-analysis 1 – Depression occurrenceGroup comparisons (12 studies, 127 effects, 2028 participants) | |||||||||||||||||||
Bruzzone, 2024 | 387 (90, 297) | 29.6 | 63.9 | EUR | MDD | Moderate all | MDD | BDI – HAM-D17 | Anx., chilhood trauma | Healthy | Blood peri or WBC | Pyroseq. PyroMark Q96 | Y | Single | 4 | GRCh38/hg38 30,236,071; 30,236,083; 30,236,088; 30,236,090 | 6090; 6088; 6083; 6071 | 4 | N |
Bakusic, 2020 | 138 (80, 58) | 45.4 | 56.5 | n/a | MDD | Moderate average | MDD | SCID | n/a | Healthy | Blood peri | Pyroseq. PyroMark Q24 | Y | Single | 23 CpG | GRCh38/hg38 GenBank NG_011747 | 6101; 6090; 6088; 6083; 6071; 6036; 6002; 5998; 5984; 5975; 5973; 5968; 5956; 5952; 5939; 5910; 5906; 5904; 5897; 5892; 5888; 5886; 5871; 5867; 5852 | 23 | N |
Schiele, 2019 | 60 (32, 28) | 34.3 | 78.3 | CA | Comord. MDD | n/a | PD | SCID | Ago., MDD, social Anx., phobias | PD without MDD | Blood peri | Pyroseq. | Y | Single | 9 | GRCh38/hg38 30,236,071; 30,236,083; 30,236,088; 30,236,090; 30,236,101; 30,236,120; 30,236,125; 30,236,141; 30,236,156 | 6156; 6141; 6125; 6120; 6101; 6090; 6088; 6083; 6071 | 9 | N |
Lam, 2018 | \(302_{{(95,\, {207})}^{\rm{b}}}\) | 73.2 | 62.5 | CA | MDD | > Mild all + Moderate average | MDD | MINI – CES-D | Dementia, Anx., ischemic diseases, cancer, thyroid disease, diabetes, asthma | Healthy elders | WBC | MALDI-based Agena | N | Averaged per unit | 10 units/20 CpG | GRCh38/hg38 Reg.: 30,235,734– 30,236,068 | 6036; 5984; 5975/73; 5956/52; 5939; 5909/891; 5886/84; 5870/60; 5795; 5768/65 | 10 | N |
Schneider, 2018 | 298 (122, 176) | 36.3 | 53 | EUR | MDD | Moderate average | MDD | SCID | n/a | Healthy | Blood peri | BS - PCR EZ-DNA methylation kit -ESME software | Y | Single | 8d | GRCh38/hg38 - AluJb | 6593; 6587; 6571; 6511; 6509; 6500; 6496; | 7 | N |
Shi, 2017 | 151 (96, 55) | 31 med. (21-47) | 60.3 | CHA | MDD | Severe all | MDD | SCID – HAM-D24 | n/a | Healthy | Blood peri | Pyroseq. Pyro Q-CpG | Y | Single | 6 | GRCh37/hg19 28,562,957; 28,562,970; 28,562,974; 28,562,986; 28,562,991; 28,562,993 | 5975; 5973; 5968; 5956; 5952; 5939 | 6 | N |
Iga, 2016 | 57 (28, 29) | 43.6 | 71.9 | JA | MDD | Moderate average | MDD | SCID | Diabetes, hypertension, gastritis | Healthy | WBC | Pyroseq. PyroMark Q24 | Y | Single | 9 | GRCh37/ hg19 GenBank NC_000017.10 | 6156; 6141; 6125; 6120; 6101; 6090; 6088; 6083; 6071 | 9 | Y |
Won, 2016 | 84 (35, 49) | 40.8 | 70.2 | KA | MDD | Moderate average | MDD | SCID | Suicide, drug abuse | Healthy | Blood peri | Pyroseq. Pyrosequencing Assay Design Software | Y | Single | 5 | n/a – −34 to −5 bp relative to the TSS | 5732; 5728; 5714; 5705; 5703 | 5 | N |
Booij, 2015 | 69 (33, 36) | 37.7 | 63.8 | n/a | MDD | Severe all | MDD | SCID | n/a NO psychiatric comorb. | Healthy | Blood peri | Pyroseq. PyroMark Q24 | Y | Average all + specific sites | 11d | n/a 214 to 625 bp region upstream of TSS | 6167–6036; 6167/56; 6090/88; | 3 | Y |
Okada, 2014 | 100 (50, 50) | 40.3 | 46 | JA | MDD | Moderate all | MDD | MINI | n/a | Healthy | Blood peri | MALDI-based Agena | N | Single | 29 units / 47 CpG | GRCh37/hg19 Reg.: 28,562,388– 28,563,186 | spe. CpG sites: n/a Reg: 5 370 - 6 168 | 29 | N |
Kim, 2013 | 286 (80, 206) | 64.5 | 40.9 | n/a | PSD | Moderate average | PSD | MINI | n/a NO dementia, Parkinson, brain tumor, epilepsy, psychosis, substance dependence; severe physical illnesses limiting movement prior PSD | Healthy | Blood peri | Pyroseq. Pyro Q-CpG | Y | Single | 7 | n/a −479 to −350 bp relative to the TSS | 6141; 6125; 6101; 6090; 6088; 6083; 6071 | 7 | N |
Xu, 2013 | 96 (36, 60) | 28.2 | 80.2 | CHA | Comorb. depr. | Moderate average | SLE | SCID | Depr. | SLE without depr. | WBC | BS - PCR Shanghai Sangon Biological Engineering Technology & Services Co. Ltd. | Y | Single | 15 d | n/a GenBank: EF179203.1 | 7150; 7146; 7133; 7105; 7097; 7080; 7070; 7068; 7066; 7044; 7036; 7029; 7018; 7002; 6995 | 15 | N |
Systematic review only - Depression occurrence Group comparisons (2 studies, 413 participants) | |||||||||||||||||||
Moon, 2022 | 221 | 64.0 | 78.2 | KA | MDD | Moderate all | MDD | HAM-D17 | n/a NO cancer, unstable psychiatric features, history of substance abuse, neurologic illnesses, SCZ, BD, primary diagnoses of adjustment disorder, PTSD, psychotic sympt., pregnancy | Only MDD | Blood peri | Pyroseq. PyroMark | Y | Single | 9 | GRCh37/ hg19 28,563,090; 28,563,102; 28 563,107; 28,563,109; 28,563,120; 28,563,139; 28,563,144; 28,563,160; 28,563,175 | 6156; 6141; 6125; 6120; 6101; 6090; 6088; 6083; 6071 | - | Y |
Philibert, 2008 | 192 (25, 167) | 40.6 | 50 | AFA, HA, others | MDD | n/a | MDD | SCID | Alcohol dependence | Healthy | lymphoblast cell lines | BS - PCR MassARRAY | N | - | 53 units/ 71 CpG | NCBI36/hg18 Reg.: 25,586,414 – 25,587,412 | Reg.: 5270–6268 | - | Y |
Meta-analysis 2 – Depression severity Correlations/Regressions (14 studies, 116 effects, 2296 participants) | |||||||||||||||||||
Rivera, 2024 | 91 | 24.0 | 50.5 | RWD | Depr. Sympt. + MDD | Mild average | No diagnosis or MDD | PROMIS-29 | Childhood adversity | MDD + Healthy | capillary Blood peri | Microarray Illumina Infinium MethylationEPIC microarray | N not in this case | Average | n/a | n/a | n/a | 1 | N |
Comtois-Cabana, 2023 | 156 | 24.1 | 0 | n/a | Depr. Sympt. + MDD | Mild average | No diagnosis or MDD | BDI-II | Drug use | MDD + Healthy | Saliva | BS – PCR EZ-DNA methylation Gold Kit - EpiTYPER MassARRAY | Y | Average per unit | 31 units/87 CpG | GRCH37/hg19 Reg. 1: 28,563,054– 28,563,424; Reg. 2: 28,562,783– 28,563,020; Reg. 3: 28,562,388– 28,562,751 | 6406; 6235; 6167; 6141; 6036; 5896/91; 5886/84/70; 5866; 5851; 5845/43; 5837–5829; 5808, 5768/65; 5733/31; 5719–5699; 5688–5673; 5667/65; 5654; 5641; 5 578; 5554/49; 5518/11; 5503; 5489; 5481/74/71; 5456; 5447; 5417; 5394; 5383; 5374/70 | 31 | N |
Vidovic, 2023 | 25 | 52.1 | 64.0 | CA | MDD | Moderate to Severe average | MDD | BDI-II – IDS-C | Anx. | Only MDD | Blood peri | BS – PCR EpiTect Fast Bisulfite - MiniSeq Mid Output Kit | N | Average | 2 | GRCH37/hg19 Reg. 1: 28,562,753– 28,563,050 Reg. 2: 28,563,277– 28,563,552 | Reg. 1: 5735–6032 Reg. 2: 6259 – 6534 | 2c | N |
Timmers, 2022 | 117 | 46.6 | 65.8 | n/a | Depr. Sympt. + MDD | Mild average | Dystonia | BDI | Depr. | Dystonia with/without Depr. Sympt. | Blood peri | Pyroseq. PyroMark Q24 | Y | Single | 20 | n/a −213 to −69 bp relative to the transcriptional start | 5910; 5906; 5904; 5896; 5891; 5886; 5884; 5870; 5865; 5850; 5845; 5843; 5837; 5835; 5832; 5830; 5808; 5796; 5779; 5776 | 20 | N |
Sanwald, 2021 | 146 | 38.7 | 65.1 | n/a | MDD | Moderate to Severe average | MDD | BDI-II – MADRS | Alcohol abuse (n=2), sexual dysfunction (n=1) | Only MDD | Blood peri | MALDI-based Agena | N | Average2 factors | 29 units / 71 CpG | GRCh38/hg38 Reg. 1 : 30,235,345– 30,235,765 Reg. 2: 30,235,734– 30,236,068 | Reg. 1 : 5345–5765 Reg. 2: 5734–6068 | 2c | N |
Schiele, 2021 | 236 | 34.3 | 78.3 | CA | MDD treated since min.6w | Severe average | MDD | BDI – HAM-D21 | PD and/or ago. (n=11), social phobia (n=7), stress-related disorder (n=5), somatoform (n=7), OCD (n=2) | Only MDD | Blood peri | BS – PCR Epigenetic Sequencing Methylation analysis software | Y | Average | 9 | GRCh38/hg38 30,236,071; 30,236,083; 30,236,088; 30,236,090; 30,236,101; 30,236,120; 30,236,125; 30,236,141; 30,236,156 | Reg.: 6071–6156 | 1c | N |
Bakusic, 2020 | 138 | 45.4 | 56.5 | n/a | MDD | Moderate average | MDD | HAM-D17 | n/a | MDD + Healthy | Blood peri | Pyroseq. PyroMark Q24 | Y | Average all + specific sites | 5 units / 23 CpG | GRCh38/hg38 GenBank NG_011747 | 6101; 6088; 6101/071 | 3 | N |
Shi, 2017 | 96 | 31 med. (21–47) | 60.3 | CHA | MDD | Severe all | MDD | HAM-D24 | n/a | Only MDD | Blood peri | Pyroseq. Pyro Q-CpG | Y | Single | 6 | GRCh37/hg19 28,562,957; 28,562,970; 28,562,974; 28,562,986; 28,562,991; 28,562,993 | 5975; 5973; 5968; 5956; 5952; 5939 | 6 | N |
Iga, 2016 | 28 | 45 | 71.4 | JA | MDD | Moderate average | MDD | HAM-D17 | Diabetes, hypertension, gastritis | Only MDD | WBC | Pyroseq. PyroMark Q24 | Y | Single | 9 | GRCh37/hg19 GenBank NC_000017.10 | 6156; 6141; 6125; 6120; 6101; 6090; 6088; 6083; 6071 | 9 | Y |
Duman, 2015 | 67 | 28.5a | 0 | CA | Depr. Sympt. | Mild average | - | BDI-II | - | Only MDD | WBC | MALDI-based Sequenom Epityper | N | Average all + per factor | 3 units / 26 CpG | n/a | Reg.: 5270– 6268 3 factors | 3 | Y |
Lei, 2015 | 99 | 48.3 | 100 | AFA | Depr. Sympt. | Mild average | - | CES-D | n/a | Healthy | Blood peri | Microarray Illumina 450K Human Methylation Beadchip | N not in this case | Average | 7 units | n/a Cg27569822, Cg10901968, Cg26741280, Cg25725890, Cg05016953, Cg14692377, Cg03363743 | 6139/090 + 6120/071 + 6101/50 + 6037/5 988 + 5796/47 + 5668/19 + 5457/08 | 1 | N |
van der Knaap, 2015 | 939 | 16.2 | 51.7 | Dutch | Depr. Sympt.. | n/a | - | YSR | Internalizing, Anx., Depr. | Healthy | Blood peri | MALDI-based Agena | N | Average | 11 units | GRCh37/hg19 Reg.: 28,562,388– 28,563,186 | Reg: 5370– 6168 | 1 | N |
Okada, 2014 | 50 | 40.3 | 46 | JA | MDD | Moderate all | MDD | HAM-D17 | n/a | Only MDD | Blood peri | MALDI-based Agena | N | Average per unit | 29 units/47 CpG | GRCh37/hg19 Reg.: 28,562,388– 28,563,186 | spe. CpG sites: n/aReg: 5370– 6168 | 29 | N |
Kang, 2013 | 108 | 54.9 | 76.4 | n/a | MDD | Moderate average | MDD | HAM-D17 | n/a | Only MDD | Blood peri | Pyroseq. Pyro Q-CpG | Y | Single | 7 CpG | n/a −479 to −350 bp relative to the TSS; | 6141; 6125; 6101; 6090; 6088; 6083; 6071 | 7 | N |