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. 2025 Apr 11;22(4):341–356. doi: 10.30773/pi.2024.0152

Table 1.

A summary of blood biomarkers in diagnosing major depressive disorder in adults

Study Category Comparison method Cohort (M/F), age (yr) Biomarkers Medicationnaive AUC Sensitivity/specificity (%)
Zhang et al. [17] (2022) Transcriptomics Mini-International Neuropsychiatric Interview, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale HC=19 (6/13), Age: 22.74 CircularRNA–hsa_circ_0002473, hsa_circ_0079651, hsa_circ_0137187, hsa_circ_0006010, and hsa_circ_0113010 Y Hsa_circ_0002473=0.8619 Hsa_circ_0002473=78.57/86.67
Hsa_circ_0079651=0.7112 Hsa_circ_0079651=51.72/93.75
MDD=29 (8/21), Age: 22.1 Hsa_circ_0137187=0.8190 Hsa_circ_0137187=89.29/66.67
Hsa_circ_0006010=0.8367 Hsa_circ_0006010=85.71/78.57
Hsa_circ_0113010=0.7091 Hsa_circ_0113010=51.72/93.75
Lin et al. [16] (2019) Transcriptomics Hamilton Depression Rating Scale HC=125 (51/74), Age: 36.8 mRNA–Serine racemase (SSR), phosphoserine aminotransferase 1 (PSAT1), glycine C-acetyltransferase (GCAT), glutamate decarboxylase 1 (GAD1), and neuregulin 1 (NRG1) Y 0.889 0.960/0.640
MDD=25 (9/16), Age: 35.6
Gecys et al. [15] (2022) Transcriptomics Mini-International Neuropsychiatric Interview, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification Discovery cohort: mRNA - hsa-let-7e-5p, hsa-miR-125a-5p N hsa-let-7e-5p: 0.66 -
 HC=37 (8/29), Age: 21–65 hsa-miR-125a-5p: 0.600
 MDD=48 (12/36), Age: 19–75
Validation cohort:
 HC=74 (20/54), Age: 21–68
 MDD=84 (16/68), Age: 19–75
Fan et al. [14] (2014) Transcriptomics DSM-IV, Hamilton Depression Rating Score HC=46 (20/26), Age: 33.35 miRNA–miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, miRNA-4743 N Combined: 0.636 Combined: 54.4/79.0
MDD=81 (35/46), Age: 33.28
Min et al. [20] (2023) Metabolomics DSM-IV, Hamilton Depression Rating Score HC=41 (21/20), Age: 25–35 TNF-α, IL-6 Y TNF-α=0.733 -
MDD=113 (42/71), Age: 24–42 IL-6=0.783
Kim et al. [19] (2021) Metabolomics Beck Depression Index, Hamilton Depression Rating Score HC=50 (24/26), Age: 24.8 IL-17, IL1β, CRP Y Male: IL-17=0.766 Male: IL-17=87.0/57.1
Female: IL-1β=0.697 Female: IL-1β=85.0/53.4
MDD=50 (23/27), Age: 24.18 IL-6 level=0.709 IL-6 level=51.9/84.6
CRP=0.688 CRP=100/38.4
Zhang et al. [23] (2022) Metabolomics DSM-IV, Hamilton Depression Rating Score, Hamilton Anxiety Rating Scale HC=25 (0/25), Age: 18–24 20 Lipids* N 0.897 -
MDD=28 (0/28), Age: 30–43
Levada et al. [21] (2020) Metabolomics DSM-5 HC=47 (20/27), Age: 37.8 IGF-1 N 0.820 83/71
MDD=78 (30/480), Age: 38.2
Kageyama et al. [18] (2018) Metabolomics DSM-IV, Hamilton Depression Rating Score Discovery: Nervonic acid N - Overall: 67.1/62.2
 HC=19 (10/9), Age: 36.1
 MDD=9 (3/6), Age: 39.1
 SZ=17 (8/9), Age: 33.6
 BD=6 (1/5), Age: 41.8
Validation set:
 HC=100 (46/54), Age: 49.2
 MDD=45 (19/26), Age: 54.0
 SZ=115 (59/56), Age: 39
 BD=71 (37/34), Age: 45.2
Pan et al. [22] (2018) Metabolomics DSM-IV, Hamilton Depression Rating Score Discovery set: Dopamine, GABA, Tyramine, Kyneuramine N Discovery: 0.968 Discovery: 94.1/98.0
 HC=50 (25/25), Age: 34–36 Validation: 0.953 Validation: 93.9/87.5
 MDD=50 (24/26), Age: 37–39
Validation set:
 HC=40 (22/18), Age: 37–39
 MDD=49 (23/26), Age: 36–39
 BD=30 (13/17), Age: 24–46
Zheng et al. [24] (2016) Metabolomics DSM-IV Discovery set: Peripheral Blood Mononuclear Cells (PBMC)–top 17 discriminants† Y Discovery: 0.926
 HC=50 (22/28), Age: 39.7 Validation: 0.870
 MDD=50 (20/30), Age: 38.9
Validation set:
 HC=56 (24/32), Age: 31.4 (14.1)
 MDD=58 (19/39), Age: 39.5 (13.8)
 SZ=40 (9/31), Age: 27.5 (12.5)
Liu et al. [31] (2016) Metabolomics DSM-IV, Hamilton Depression Rating Scale Discovery set: 17 Lipids‡ N 0.863 -
 HC=60 (30/30), Age: 43.98
 MDD=60 (30/30), Age: 42.42
Validation set:
 HC=52 (26/26), Age: 33.67
 MDD=75 (40/35), Age: 36.04
Ghanbarirad et al. [26] (2021) Genomics DSM-5 HC=100 (68/32), Age: 31.9 Myelin Transcription Factor 1 (MYT1) N 0.973 0.96/0.85
MDD=100 (67/33), Age: 35.2
BD=100 (68/32), Age: 27.1
Chiou and Huang [25] (2019) Genomics Hamilton Depression Rating Scale HC=290 (143/297), Age: 31.3 BDNF Y Males: 0.652 Males: 81.1/48.5
MDD=273 (66/207), Age: 39.4
Numata et al. [28] (2015) Genomics Hamilton Depression Rating Scale Discovery set: DNA Methylation of peripheral leukocytes–top 18 site discriminants Y - 100/100
 HC=19 (2/17), Age: 42.4
 MDD=20 (2/18), Age: 44.2
Validation set:
 HC=12 (3/9), Age: 44.3 (10.8)
 MDD=12 (3/9), Age: 45.5
Karlović et al. [27] (2013) Genomics DSM-IV, Hamilton Depression Rating Scale HC=142 (76/66), Age: 46.5 BDNF N 0.892 83.9/93.0
MDD=122 (56/66), Age: 45.8
Jiang et al. [30] (2017) Combined DSM-IV, Hamilton Depression Rating Scale HC=35 (19/16), Age: 56.74 tPA, BDNF, Tropomyosin receptor kinase B, proBDNF, neurotrophin receptor p75NTR Y 0.977 88.1/92.7
MDD=35 (11/24), Age: 43.97
Bilello et al. [29] (2015) Combined DSM-IV, Hamilton Depression Rating Scale HC=86 (46/40), Age: 20–72 Alpha1 antitrypsin, apolipoprotein CIII, BDNF, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin, soluble tumor necrosis factor alpha receptor type II N 0.963 92/93
MDD=68 (34/34), Age: 19–68

Value of age are presented as mean, mean (standard deviation), or range.

*

Cer(d15:1/25:2), Cer(d18:1/16:0), Cer(d18:1/24:0), Cer(d40:1), Cer(d41:1 + O), Cer(m34:0 + O), Cer(m38:2 + O) and PI(16:1), Cer(d32:4), CerG2GNAc1(d32:1), CerG2GNAc1(d36:1), CerG2GNAc1(d38:4), GM2(d34:5), GM3(t39:6), PC(18:0/16:0), PC(20:1e/18:2), PC(26:2e), PC(40:10), TG(18:1/18:2/22:4), TG(20:0/18:1/18:1);

†

octanoic acid, hydroxylamine, benzoic acid, γ-aminobutyric acid, homoserine, malonic acid, isoleucine, lanosterol, valine, sorbitol, creatinine, ribulose 5-phosphate, ethanolamine, malic acid, fumaric acid, γ-tocopherol and dopamine;

‡

lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), 1-O-alkyl-2-acyl-PE (PE O), 1-O-alkyl-2-acyl-PC (PC O), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG).

M, male; F, female; AUC, area under the curve; HC, healthy control; MDD, major depressive disorder; N, no; Y, yes; mRNA, messenger RNA; miRNA, microRNA; TNF, tumor necrosis factor; IL, interleukin; DSM, Diagnostic and Statistical Manual of Mental Disorders; CRP, C-reactive protein; IGF, insulin-like growth factor; SZ, schizophrenia; BD, bipolar disorder; GABA, gamma-aminobutyric acid