Table 1 Effect sizes of blood metabolites between patients with major depressive disorder and controls.

From: An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder

Metabolites

N Comparisons

N MDD/CON

SMD (95% CI)

p valuea (overall)

I2

p valueb (heterogeneity)

p valuec (Egger)

Kynurenic acid

13

797/653

−0.42 (−0.52 to −0.31)

<0.001

1.2%

0.434

0.647

2-Hydroxybutyric acid

3

76/83

1.02 (0.69 to 1.36)

<0.001

0.0%

0.652

0.990

Dodecanoic acid

4

151/114

−0.73 (−0.99 to −0.48)

<0.001

0.0%

0.544

0.495

25-Hydroxyvitamin D

3

1130/521

−0.29 (−0.39 to −0.18)

<0.001

0.0%

0.811

0.060

Tyramine

3

133/121

1.12 (0.70 to 1.55)

<0.001

58.8%

0.089

0.091

Phosphatidylcholine (32:1)

3

150/130

0.56 (0.32 to 0.80)

<0.001

0.0%

0.482

0.117

l-Tryptophan

26

2390/2928

−0.46 (−0.66 to −0.26)

<0.001

87.8%

<0.001

0.004

Myo-inositol

3

113/77

−0.79 (−1.17 to −0.41)

<0.001

28.3%

0.248

0.619

Linoleic acid

5

148/104

−0.99 (−1.46 to −0.51)

<0.001

63.4%

0.027

0.348

Oleic acid

5

148/104

−0.84 (−1.31 to −0.36)

0.001

63.6%

0.027

0.368

Taurochenodesoxycholic acid

4

176/180

0.33 (0.11 to 0.54)

0.003

0.0%

0.446

0.320

Creatinine

5

186/175

−1.79 (−3.02 to −0.56)

0.004

95.7%

<0.001

0.321

l-Glutamine

8

329/287

−1.28 (−2.19 to −0.37)

0.006

95.8%

<0.001

0.067

Asymmetric dimethylarginine

4

191/342

2.52 (0.68 to 4.36)

0.007

97.9%

<0.001

0.202

l-Acetylcarnitine

3

138/109

−2.06 (−3.58 to −0.54)

0.008

95.4%

<0.001

0.106

Hypoxanthine

6

259/386

−0.70 (−1.21 to −0.18)

0.009

85.9%

<0.001

0.391

Palmitic acid

4

139/94

−0.69 (−1.23 to −0.16)

0.011

71.2%

0.015

0.288

Pyruvic acid

3

101/92

−0.92 (−1.68 to −0.17)

0.017

80.7%

0.006

0.370

l-Asparagine

6

221/195

−1.33 (−2.45 to −0.21)

0.020

95.7%

<0.001

0.079

Palmitoleic acid

3

93/69

−0.90 (−1.70 to −0.10)

0.027

79.8%

0.007

0.228

l-Methionine

8

356/306

−0.73 (−1.40 to −0.06)

0.032

93.4%

<0.001

0.299

l-Serine

8

296/245

−0.90 (−1.73 to −0.07)

0.034

94.5%

<0.001

0.034

Taurine

6

270/218

−0.33 (−0.65 to −0.01)

0.043

65.0%

0.014

0.399

Glycine

8

325/262

−0.91 (−1.82 to 0.01)

0.051

95.7%

<0.001

0.096

Capric acid

4

151/114

−1.31 (−2.65 to 0.03)

0.056

95.6%

<0.001

0.033

l-Lysine

6

221/195

−1.03 (−2.10 to 0.04)

0.059

95.4%

<0.001

0.053

Citric acid

5

143/135

−0.96 (−1.97 to 0.05)

0.063

92.5%

<0.001

0.571

l-Valine

8

325/262

−0.71 (−1.48 to 0.06)

0.071

94.3%

<0.001

0.049

l-Kynurenine

18

2020/2595

−0.17 (−0.36 to 0.02)

0.077

81.9%

<0.001

0.948

l-Phenylalanine

7

271/245

0.68 (−0.08 to 1.44)

0.079

93.4%

<0.001

0.133

l-Threonine

8

296/245

−0.64 (−1.36 to 0.09)

0.085

93.1%

<0.001

0.088

Urea

3

113/89

−2.11 (−4.59 to 0.38)

0.097

97.9%

<0.001

0.018

Gluconic acid

3

89/75

−0.27 (−0.58 to 0.05)

0.099

0.0%

0.793

0.412

l-Tyrosine

8

329/287

−0.31 (−0.69 to 0.06)

0.099

79.4%

<0.001

0.954

Aminoadipic acid

5

190/136

1.15 (−0.22 to 2.51)

0.100

96.4%

<0.001

0.032

Gamma-aminobutyric acid

7

246/184

0.81 (−0.17 to 1.79)

0.104

94.5%

<0.001

0.775

Creatine

5

186/175

−0.72 (−1.61 to 0.16)

0.108

93.2%

<0.001

0.385

l-Alanine

8

325/262

−0.67 (−1.48 to 0.15)

0.109

94.8%

<0.001

0.060

Phosphatidylethanolamine (34:2)

3

150/130

0.38 (−0.12 to 0.87)

0.136

73.0%

0.025

0.146

Stearic acid

3

64/54

−0.42 (−1.00 to 0.16)

0.152

47.7%

0.148

0.938

l-Isoleucine

7

279/237

−0.58 (−1.40 to 0.25)

0.171

94.4%

<0.001

0.113

Succinic acid

4

163/139

0.69 (−0.35 to 1.74)

0.194

94.4%

<0.001

0.001

Ornithine

8

370/498

−0.31 (−0.78 to 0.17)

0.205

89.1%

<0.001

0.236

Homovanillic acid

3

117/114

1.36 (−0.80 to 3.52)

0.216

97.8%

<0.001

0.316

Glyceric acid

4

122/99

1.29 (−0.76 to 3.35)

0.217

97.1%

<0.001

0.613

l-Leucine

8

325/262

−0.14 (−0.37 to 0.08)

0.217

41.5%

0.102

0.870

Adenosine diphosphate

3

76/83

2.01 (−1.20 to 5.22)

0.220

98.0%

<0.001

0.448

l-Malic acid

3

76/83

0.87 (−0.57 to 2.31)

0.235

93.7%

<0.001

0.908

Indoleacetic acid

3

82/83

1.49 (−1.03 to 4.00)

0.247

97.6%

<0.001

0.300

Symmetric dimethylarginine

3

166/317

1.05 (−0.75 to 2.84)

0.253

97.7%

<0.001

0.384

Arachidonic acid

3

93/69

−0.52 (−1.42 to 0.37)

0.253

84.4%

0.002

0.435

Pyroglutamic acid

5

174/149

−0.64 (−1.76 to 0.49)

0.267

95.1%

<0.001

0.680

Serotonin

5

144/184

−0.26 (−0.76 to 0.23)

0.301

77.9%

0.001

0.575

Dimethylglycine

3

76/83

1.18 (−1.08 to 3.44)

0.305

97.0%

<0.001

0.543

l-Carnitine

3

138/109

−0.40 (−1.18 to 0.37)

0.308

88.2%

<0.001

0.587

Isocitric acid

4

122/108

1.06 (−0.98 to 3.10)

0.308

97.4%

<0.001

0.186

Choline

4

134/125

0.75 (−0.72 to 2.22)

0.316

96.2%

<0.001

0.253

Glycoursodeoxycholic acid

3

144/130

0.19 (−0.19 to 0.58)

0.327

53.5%

0.116

0.800

Ethanolamine

5

208/170

−0.94 (−2.84 to 0.97)

0.336

98.1%

<0.001

0.613

cis-Aconitic acid

3

76/83

1.42 (−1.50 to 4.35)

0.341

97.9%

<0.001

0.304

1-Methylhistidine

4

161/111

−0.33 (−1.01 to 0.35)

0.342

85.7%

<0.001

0.540

l-Lactic acid

5

180/150

−0.37 (−1.23 to 0.49)

0.400

92.3%

<0.001

0.731

Deoxycholic acid

3

144/130

−0.17 (−0.60 to 0.25)

0.427

61.1%

0.076

0.985

O-Phosphoethanolamine

4

161/111

−0.21 (−0.75 to 0.33)

0.448

78.3%

0.003

0.814

5-Hydroxylysine

3

135/86

0.73 (−1.22 to 2.68)

0.464

97.3%

<0.001

0.107

Citrulline

8

349/473

0.18 (−0.31 to 0.68)

0.466

89.3%

<0.001

0.533

l-Proline

6

216/155

−0.35 (−1.40 to 0.70)

0.510

94.9%

<0.001

0.068

l-alpha-aminobutyric acid

3

145/112

0.17 (−0.40 to 0.73)

0.563

77.4%

0.012

0.416

Sarcosine

4

144/105

−0.20 (−0.95 to 0.55)

0.602

86.5%

<0.001

0.794

Quinolinic acid

10

453/415

−0.06 (−0.32 to 0.20)

0.660

69.7%

<0.001

0.500

3-Hydroxybutyric acid

4

134/125

0.11 (−0.41 to 0.63)

0.670

74.6%

0.008

0.821

Betaine

4

128/133

0.26 (−0.99 to 1.51)

0.679

95.3%

<0.001

0.410

4-Hydroxyproline

5

170/130

−0.16 (−0.97 to 0.65)

0.701

90.3%

<0.001

0.794

l-Histidine

7

279/237

0.09 (−0.51 to 0.70)

0.763

90.2%

<0.001

0.479

l-Aspartic acid

7

262/211

0.09 (−0.53 to 0.72)

0.771

90.0%

<0.001

0.991

Phosphatidylcholine (32:0)

3

150/130

0.08 (−0.51 to 0.66)

0.799

80.6%

0.006

0.694

Hydroxykynurenine

6

261/300

0.03 (−0.19 to 0.25)

0.804

37.7%

0.155

0.615

l-Cystine

3

135/86

0.25 (−2.70 to 3.20)

0.870

98.5%

<0.001

0.435

l-Glutamic acid

7

271/245

0.06 (−0.73 to 0.86)

0.873

94.1%

<0.001

0.492

3-Aminoisobutanoic acid

4

161/111

−0.06 (−1.03 to 0.92)

0.911

93.0%

<0.001

0.932

beta-Alanine

5

170/130

−0.02 (−0.47 to 0.43)

0.944

70.5%

0.009

0.697

l-Arginine

9

404/498

−0.01 (−0.73 to 0.70)

0.970

95.2%

<0.001

0.578

Cholesterol

3

113/86

0.00 (−1.17 to 1.16)

0.997

92.3%

<0.001

0.867

  1. CI confidence interval, CON control, MDD major depressive disorder, N number, SMD standardized mean difference
  2. ap value for between-group effect sizes
  3. bp value for heterogeneity calculated using a chi-square analysis
  4. cp value for Egger’s test. A p < 0.1 is indicative of this asymmetry
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