Table 1. Biomarkers in the Cerebrospinal Fluid (CSF) in Individuals With Depression Compared With Healthy Control Individuals Measured in 2 or More Studiesa.
| CSF marker | No. of studies | Individuals with depression, No. | Control individuals, No. | SMD (95% CI) | P value | I2, % |
|---|---|---|---|---|---|---|
| Neurotransmitters and their metabolites | ||||||
| HVA | 17 | 684 | 681 | −0.26 (−0.39 to −0.14) | <.001 | 11 |
| 5-HIAA | 15 | 566 | 558 | −0.04 (−0.28 to 0.19) | .72 | 66 |
| MHPG | 14 | 581 | 517 | 0.11 (−0.14 to 0.36) | .38 | 70 |
| GABA | 4 | 180 | 111 | −0.50 (−0.92 to −0.08) | .02 | 55 |
| Glutamate | 4 | 90 | 93 | 0.21 (−0.79 to 1.21) | .68 | 88 |
| Glutamine | 4 | 90 | 94 | 0.33 (−0.15 to 0.82) | .18 | 54 |
| Hormones | ||||||
| Cortisol | 2 | 77 | 81 | 1.23 (0.89 to 1.57) | <.001 | 0 |
| Transthyretin | 2 | 25 | 39 | −0.82 (−1.37 to −0.27) | .003 | 0 |
| CRH | 8 | 169 | 210 | −0.02 (−0.39 to 0.34) | .91 | 62 |
| ACTH | 2 | 39 | 139 | 0.07 (−0.29 to 0.42) | .72 | 0 |
| Oxytocin | 2 | 36 | 39 | −0.34 (−0.79 to 0.12) | .15 | 0 |
| Vasopressin | 2 | 56 | 43 | −0.07 (−0.47 to 0.33) | .74 | 0 |
| Neuropeptides | ||||||
| Somatostatin | 5 | 130 | 113 | −1.49 (−2.53 to −0.45) | .005 | 91 |
| NPY | 5 | 172 | 101 | −0.34 (−1.37 to 0.69) | .52 | 93 |
| Substance P | 2 | 51 | 58 | 0.71 (−0.15 to 1.57) | .11 | 70 |
| CART | 2 | 69 | 30 | −0.42 (−1.04 to 0.20) | .18 | 30 |
| Orexin | 2 | 29 | 22 | −0.25 (−0.81 to 0.31) | .39 | 0 |
| Amino acids and derivates | ||||||
| D-serine | 3 | 55 | 56 | 0.43 (−0.15 to 1.02) | .14 | 52 |
| L-serine | 3 | 55 | 56 | 0.16 (−0.64 to 0.96) | .69 | 75 |
| Serine | 2 | 51 | 64 | 0.60 (−0.36 to 1.57) | .22 | 70 |
| Glycine | 3 | 79 | 83 | 0.07 (−0.38 to 0.52) | .76 | 43 |
| Tryptophan | 2 | 37 | 54 | −0.22 (−0.64 to 0.20) | .30 | 0 |
| Tyrosine | 2 | 56 | 72 | −0.07 (−0.45 to 0.31) | .71 | 9 |
| Aspartate | 2 | 33 | 47 | −0.79 (−2.44 to 0.87) | .35 | 88 |
| Methionine | 2 | 56 | 72 | −0.17 (−0.52 to 0.18) | .35 | 0 |
| Ascorbic acid | 2 | 42 | 36 | 0.40 (−0.67 to 1.48) | .46 | 81 |
| Inflammatory markers | ||||||
| IL-6 | 7 | 156 | 229 | 0.35 (0.12 to 0.59) | .003 | 16 |
| IL-8 | 5 | 234 | 297 | 0.12 (−0.21 to 0.45) | .46 | 66 |
| TNF-α | 2 | 50 | 72 | 0.23 (−0.13 to 0.59) | .21 | 0 |
| White cell count | 3 | 184 | 195 | 0.05 (−0.23 to 0.33) | .72 | 42 |
| MMP-3 | 2 | 141 | 148 | 0.14 (−0.09 to 0.38) | .22 | 0 |
| Blood-brain barrier permeability | ||||||
| Total protein | 5 | 220 | 261 | 0.53 (0.35 to 0.72) | <.001 | 0 |
| Albumin ratio | 2 | 40 | 81 | 0.51 (−0.26 to 1.29) | .19 | 62 |
| Glucose | 2 | 99 | 114 | 0.04 (−0.23 to 0.31) | .78 | 0 |
| Synaptic plasticity | ||||||
| BDNF | 3 | 46 | 62 | −0.58 (−0.97 to −0.19) | .004 | 0 |
| NCAM | 2 | 187 | 229 | −0.11 (−0.31 to 0.08) | .24 | 0 |
| Neurodegeneration | ||||||
| Amyloid-β 40 | 3 | 71 | 81 | −0.80 (−1.14 to −0.46) | <.001 | 0 |
| Total τ | 9 | 153 | 283 | −0.32 (−0.70 to 0.06) | .10 | 66 |
| P-τ 181 | 6 | 114 | 154 | −0.02 (−0.28 to 0.24) | .88 | 0 |
| Amyloid-β 42 | 8 | 140 | 248 | 0.07 (−0.48 to 0.62) | .80 | 82 |
| Neurogranin | 2 | 34 | 63 | −0.17 (−0.65 to 0.32) | .50 | 0 |
| NfL | 2 | 27 | 85 | 0.01 (−1.38 to 1.39) | .99 | 88 |
Abbreviations: ACTH, adrenocorticotropic hormone; BDNF, brain-derived neurotrophic factor; CART, cocaine- and amphetamine-regulated transcript; CRH, corticotropin-releasing hormone; GABA, γ-aminobutyric acid; HIAA, hydroxyindoleacetic acid; HVA, homovanillic acid; IL, interleukin; MHPG, 3-methoxy–4-hydroxyphenylglycol; MMP, matrix metalloproteinase; NCAM, neural cell adhesion molecule; NfL, neurofilament light; NPY, neuropeptide Y; SMD, standard mean difference; TNF, tumor necrosis factor.
a
The table displays only results from random-effects models.