The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index; none of the 61 sources its claims cite is checked for support yet.
Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies
Open accessAbstract
Objective: To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HC s). Method: The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random‐effects models. Result: Eighty‐two studies comprising 3212 participants with MDD and 2798 HC s met inclusion criteria. Peripheral levels of interleukin‐6 (IL‐6), tumor necrosis factor (TNF)‐alpha, IL‐10, the soluble IL‐2 receptor, C‐C chemokine ligand 2, IL‐13, IL‐18, IL‐12, the IL‐1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HC s, whereas interferon‐gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL‐1β, IL‐2, IL‐4, IL‐8, the soluble IL‐6 receptor (sIL‐6R), IL‐5, CCL‐3, IL‐17, and transforming growth factor‐beta 1 were not significantly altered in individuals with MDD compared to HC s. Heterogeneity was large (I2: 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). Conclusion: Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.
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110 Own result · 46 Not checked yet · 12 Own method · 9 Own interpretation
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of IFN-γ · plain
“IL-10 levels were investigated in 17 studies, and levels were significantly higher in the MDD group compared to HCs, with a small ES (g = 0.375, P = 0.045)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of IFN-γ · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of TNF-α · plain
“TNF-α was investigated across 42 studies, and levels were significantly higher in the MDD group compared to HCs, while there was evidence of small-study effects (g = 0.638; P < 0.001; Table 1 and Figure 2B)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelationaln = 3,212 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of TNF-α · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of IL-6 · plain
“Participants with MDD had higher concentrations compared to HCs (g = 0.621; P < 0.001; Table 1 and Figure 2A).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelationaln = 1,587 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of IL-6 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of C-C chemokine ligand 2 (CCL-2) · plain
“Levels of CCL-2 were significantly higher in participants with MDD compared to HCs with a large ES (g = 1.718;P=0.045)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of C-C chemokine ligand 2 (CCL-2) · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria.”
- Also stated in: § Study Selection · plain
“Finally, 82 original studies met inclusion criteria, which provided data from 6010 participants (3212 participants with MDD and 2798 HCs).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plainn = 3,212- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Study Selection · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of IL-13 · plain
“Levels of IL-13 were significantly higher in participants with MDD compared to HCs (g= 1.836; P<0.001)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of IL-13 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of soluble IL-2 (sIL-2) receptor · plain
“We found evidence that sIL-2 receptor levels were significantly higher in the MDD group compared to HCs with a moderate ES estimate (Hedge's g = 0.735, P < 0.001)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelationaln = 3,212 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of soluble IL-2 (sIL-2) receptor · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heterogeneity was large (I 2 : 51.6 to 97.7%), and sources of heterogeneity were explored.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs”
- Also stated in: § Studies of IL-6 · plain
“sTNFR2 3 94 101 1.173 (0.409 -1.938) 0.003 83.2”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of IL-6 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Peripheral levels of IL-1β, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, transforming growth factor beta 1 were not significantly altered in individuals with MDD compared to HCs.”
- Also stated in: § Studies of IL-1β · plain
“Levels of IL-1β did not significantly differ between MDD and HC groups across 22 included studies (Hedge's g = 0.032, P = 0.847; Table 1; Supplementary Figure S1).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Studies of IL-1β · plain
- Probably not a substantial claim. 37
- It may state two separate claims as one. 32
- The quote only partly states this claim. 2
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Twenty mediators were assayed in at least 3 studies and were thus metaanalyzed.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods:
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“most studies (k=81; 98.8%) reported either the manufacturer of the assay or provided values of the coefficient of variation (CV) of the test.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Characteristics and methodological quality of included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“most studies did not provide information on illness duration (k=56; 68.3%); the remaining studies included MDD participants with illness duration of 2.97 ± 6.15 (mean ± SD) years.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Characteristics and methodological quality of included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“most studies (k=65; 79.3%) provided data regarding medication status, whereas 3 (3.7%)included only treatment-naïve (i.e., never treated with antidepressants) participants with MDD.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Characteristics and methodological quality of included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in 43 studies (52.4%) participants with MDD and HCs were age-and gender-matched”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Characteristics and methodological quality of included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subgroup analyses showed that heterogeneity was smaller in studies that measured IL-6 in serum and whole blood samples compared to plasma, while results suggest that the measurement of IL-6 with ELISA is associated with higher heterogeneity compared to other types of assay.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-6
hedgedcorrelationaln = 1,587- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The methodological quality scores of each study varied from 1 to 6 (median: 4)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Characteristics and methodological quality of included studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the cumulative meta-analysis indicates that the ES has not been consistent over time (Figure S29).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IFN-γ
hedged- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity analyses showed that the exclusion of 11 of 17 studies one-at-a-time rendered the ES estimate nonsignificant (Figure S18).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IFN-γ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean BMI of the HC group, publication year, sample size, and mean age of the MDD and HC groups emerged as potential sources of heterogeneity in meta-regression analyses (Table S3).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IFN-γ
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subgroup analyses suggested that heterogeneity was lower in studies that measured sIL2 in plasma (compared to serum) as well as in studies in which MDD and HC groups were not age and gender-matched (Table S4).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of soluble IL-2 (sIL-2) receptor
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was evidence of small-study effects, but adjustment for publication bias did not change the ES (g = -0.452;Table 1 and Figure 3A).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IFN-γ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heterogeneity was large (I 2 = 89.2%)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IFN-γ
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TNF-α was investigated across 42 studies”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of TNF-α
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“subgroup analyses suggest that heterogeneity is lower in studies that measured this immune mediator in whole blood (compared to studies which assayed IL-1β in serum or plasma) and in studies that used stimulated leucocytes (Table S4).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-1β
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was evidence of smallstudy effects (Table 1).However, the ES was not altered after adjustment for publication bias.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of C-C chemokine ligand 2 (CCL-2)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while there was evidence of small-study effects (g = 0.638; P < 0.001; Table 1 and Figure 2B); the ES was unaltered after adjustment for publication bias (Table 1).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of TNF-α
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heterogeneity was large (I 2 = 95.3%), and no evidence of small-study effects was observed (Table 1).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-13
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The heterogeneity was large (I 2 = 92.9%),and no evidence of small-study effects was observed (Table 1).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-12
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The heterogeneity was large (I 2 = 96.0%)but could not be reliably explored due to the limited number of included studies (k=6).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-13
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three studies indicate that sTNFR2 levels are higher in individuals with MDD compared to HCs with a large ES (g = 1.173;P=0.003), but high heterogeneity (I 2 = 83.2%)(Table 1; Figure 4E).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of soluble TNF receptor 2 (sTNFR2)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Peripheral levels of IL-1Ra were higher in the MDD group compared to HCs (g= 0.449; P=0.016) (Table 1; Figure 4D).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-1 receptor antagonist (IL-1Ra)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is worthy to note that IL-6 was cytokine more extensively investigated in this meta-analysis, with a consistent moderate ES observed in cumulative meta-analysis.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the ES was small and sensitivity analyses pointed to significant outliers.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, the methodological quality of included studies has varied, and in our exploratory meta-regression analyses this factor emerged as a significant moderator of differences in TNF-α levels between participants with MDD and HCs.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, this meta-analysis indicates that several cytokines and CCL-2 are elevated in MDD.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A low-grade inflammatory response characterized by increased numbers of granulocytes and monocytes (1), as well as elevated levels of acute phase reactants (for example, Creactive protein and haptoglobin) (5,6), inflammatory cytokines (7), and possibly chemokines (8) have been demonstrated in groups of individuals with MDD compared to healthy controls (HCs).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“evidence indicates that cytokines may cross the blood-brain barrier, while certain cytokines (e.g., IL-1β) may convey signals to the brain via afferent nerves like the vagus (2,4).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A meta-analysis which included twenty-four studies provided evidence that peripheral levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are significantly elevated in individuals with MDD compared to healthy controls (HCs) (7).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
What the sources say
- Not checked yetcites [7] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“some cytokines/chemokines are predominantly pro-inflammatory, whereas others are mainly anti-inflammatory, and some of these immune mediators have been increasingly implicated in neuroplasticity mechanisms (17,18).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
What the sources say
- Not checked yetcites [17] source
- Not checked yetcites [18]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“preclinical research indicating that pro-inflammatory cytokines may promote depressive-like behaviors, whereas TNF-α and IL-6 receptor knockout mice exhibit resilience to stress-induced depressive-like behaviors (9)(10)(11).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
What the sources say
- Not checked yetcites (9)(10)(11)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“melancholic depression is associated with elevated HPA axis activity (15,16)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“a recent meta-analysis estimates that ~ 25% of patients with chronic hepatitis C develop depression after treatment with the proinflammatory cytokine interferon-α (IFN-α) (12).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Introduction
What the sources say
- Not checked yetcites [12] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For statistically significant ES estimates we performed sensitivity analyses in which we excluded each study from analyses to verify whether a single study turned results non-significant or otherwise changed the direction of the ES.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, cumulative meta-analysis was performed for significant ES with at least 10 datasets.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the fail-safe N (i.e. the file drawer statistic) was used to determine how many additional studies would be necessary to turn a significant ES non-significant (32).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
What the sources say
- Not checked yetcites [32] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An a priori defined yet unpublished protocol was followed.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Effect sizes were estimated with random-effects models.”
- Also stated in: § Statistical analysis · plain
“we pooled ES using a random-effects model according to the DerSimonian and Laird method (28).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Conclusions:
What the sources say
- Not checked yetcites [28] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § Statistical analysis · plain
In the paper
“To assess publication bias, we inspected a funnel plot graph for asymmetry, and calculated the Egger's regression test for funnel plot asymmetry (30).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
What the sources say
- Not checked yetcites [30] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The trim-and-fill procedure was used to estimate the ES adjusting for publication bias (31)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
What the sources say
- Not checked yetcites [31] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Meta-regression analyses were conducted only when at least 10 studies provided moderator; this decision was made a piori because with fewer datasets this analytic tool may provide spurious results (33).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Statistical analysis
What the sources say
- Not checked yetcites [33] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The literature search, title/abstract screening, final decision on eligibility after full-text-review, and data extraction were independently performed by two investigators.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“We complied with the Preferred Reported Items for Systematic Reviews and Meta-analysis (PRISMA) statement (21).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Methods
What the sources say
- Not checked yetcites [21] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The previous meta-analysis found elevated levels of TNF-α and IL-6 in depressive patients compared to HCs (7).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [7] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A recent meta-analysis aimed to compare peripheral levels of cytokines among patients with schizophrenia, bipolar disorder, and also MDD (50).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [50] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, we a priori excluded studies in which participants with MDD had clearly identified comorbidities, and examined the influence of other relevant confounders.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“In addition, a fixed-effects models were used to estimate ESs, which may be inaccurate when heterogeneity is large (27).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [27] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, this meta-analysis included only 30 studies.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [50] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This recent meta-analysis also investigated the effects of antidepressant treatment on blood cytokine levels in patients with MDD (50).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [50] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For example, IL-6 may activate a classical pathway and a trans-signaling pathway, which may have predominantly anti-and proinflammatory activities respectively (58).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [58] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, IL-6 and IL-1β may contribute to the pathophysiology of a subset of patients with MDD via excessive release of corticotrophin releasing hormone (CRH) and by the promotion glucocorticoid receptor resistance, which may ultimately impair the negative feedback regulation of the HPA axis (59,60).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Ronald Smith was the first to propose a macrophage theory for depression in the early 1990's (63).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [63] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, previous studies found elevated levels of IFN-γ in stimulated peripheral blood mononuclear cells (PBMCs) of individuals with MDD compared to healthy controls, which may provide a more accurate measure of this cytokine (61,62).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, preclinical studies indicate that the blockade of the trafficking of peripheral monocytes to the brain reduced proinflammatory cytokine production and decreased depressive-like behaviors in rodent stress models (66).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [66]
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although we have identified some significant moderators, some possible sources of heterogeneity could not be investigated due to the lack of data across studies, while data on other potential moderators (e.g.physical activity and diet quality) (57) were not provided by included studies, and thus could not be controlled for.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [57] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A clear limitation of this meta-analysis rests on fact that the periphery may not reflect pathophysiological events in the CNS.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Notwithstanding we could not investigate whether length of disease and number of affective episodes as possible moderators of ESs estimates due to the lack of data across studies, a previous meta-analysis, which used a different definition had found suggestive that some differences in peripheral levels of cytokines may occur in acute compared to chronic MDD relative to HCs (50).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [50] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, emerging preclinical evidence and a recent theoretical framework indicates that TH17 cells could play a significant role in the biology of depression (74,75).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, our exploratory metaregressions could have limited power to detect this effect, and previous evidence indicates that antidepressant drugs may impact peripheral cytokine levels at follow-up (50).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [50] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“It is worthy to note that although a pre-defined protocol was followed, we did not publish or otherwise registered it in a public database.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the characterization of the precise peripheral immune profile associated with MDD remains a work in progress.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, technical challenges in the assessment of certain mediators (e.g.IL-2 and IFN-γ) (73) as well as differences in the standardization of assays across different laboratories could have contributed to the heterogeneity of some estimates.”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
What the sources say
- Not checked yetcites [73]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The methodological quality score devised by the authors validly measures the methodological quality of the included studies.
“We devised a score to estimate the methodological quality of each study based on the following parameters:”
The paper relies on this without support.
IFN-γ levels were often close to the limit of detection of previously available assay kits, which may lead to analytical variability.
“Furthermore, levels of IFN-γ were most often close to the limit of detection of previously available assay kits, which may lead to analytical variability.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“LLD, and especially vascular depression, is often accompanied by increased inflammation biomarkers102.”
From Mechanisms and treatment of late-life depression (2019) · cites this paper as [102]
In the citing paper
“Meta-analyses and systematic reviews show that levels of IL-1β, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL3, IL-17A, and TGF-β1 are significantly changed in depression [16,32,33,34,35].”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [35]
In the citing paper
“Recent research on circulating cytokine levels in breast cancer patients even found IL-5 levels decreased in the depressed group [35,77].”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [35]
In the citing paper
“Elomaa et al. described elevated IL-5 levels in 58 patients with MDD, though a later meta-analysis did find changes in levels of IL-5 to be inconclusive in depressed patients.”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [35]
In the citing paper
“Elomaa et al. described elevated IL-5 levels in 58 patients with MDD, though a later meta-analysis did find changes in levels of IL-5 to be inconclusive in depressed patients.”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [35]
In the citing paper
“Unsurprisingly, IL-12 was elevated in depressed patients.”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [35]
In the citing paper
“Cytokines dysregulation (especially IL-1β, IL-6, IL-10, IFN-γ, TNF-α, and transforming growth factor-β (TGF-β)) are known to involve factors that others and we associated with psychiatric disorders (Kohler et al., 2017, Miller et al., 2011, Renna et al., 2018, Poletti et al., 2019, Benedetti et al., 2017, Benedetti et al., 2020).”
From Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors (2020) · cites this paper as Kohler et al., 2017
In the citing paper
“A recent meta-analysis of 82 studies found elevated peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2 (CCL-2), IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 in patients with MDD compared to healthy controls [6].”
In the citing paper
“Meta-analytic evidence suggests that IL-6, TNF-α, IL-10, the soluble IL-2 receptor, CCL-2, IL-12, IL-13, IL-18, the IL-1 receptor antagonist, the soluble TNF receptor 2, and C-reactive protein levels are elevated in individuals with MDD compared to healthy controls [33,6,34].”
In the citing paper
“For example, the difference of IFN-gamma was not significant between MDD and controls in a study of 238 subjects35, but a later meta-analysis that includes a total of 1470 subjects found IFN-gamma to be significantly decreased in MDD patients36.”
From Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses (2019) · cites this paper as [36]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Discussion
“This meta-analysis evidenced elevated levels of CCL-2, IL-6, IL-12, TNFα, and IL-1β, which are immune mediators secreted by M1 macrophages albeit not selectively (67).”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-1β
“Levels of IL-1β did not significantly differ between MDD and HC groups across 22 included studies (Hedge's g = 0.032, P = 0.847; Table 1; Supplementary Figure S1).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of C-C chemokine ligand 2 (CCL-2)
“Levels of CCL-2 were significantly higher in participants with MDD compared to HCs with a large ES (g = 1.718;P=0.045)”
§ Peripheral cytokine and chemokine alterations in depression: an up-dated metaanalysis of 82 studies > Studies of IL-6
“CCL-2 8 285 287 1.718 (0.641 -2.794) 0.002 96.3”
Citations
Cites
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · BMJ · doi:10.1136/bmj.b2700 · Cited by 17,648
Duval, S., & Tweedie, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00455.x · Cited by 14,099
The file drawer problem and tolerance for null results.
Rosenthal, R. (1979) · Psychological Bulletin · doi:10.1037/0033-2909.86.3.638 · Cited by 9,068 · cited 1×
“, the file drawer statistic) was used to determine how many additional studies would be necessary to turn a significant ES non-significant (32).”
MethodEstimating the mean and variance from the median, range, and the size of a sample
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Metadata
- Authors
- Köhler, C. A., Freitas, T. H., Maes, M., de Andrade, N. Q., Liu, C. S., Fernandes, B. S., Stubbs, B., Solmi, M., Veronese, N., Herrmann, N., Raison, C. L., Miller, B. J., Lanctôt, K. L., & Carvalho, A. F.
- Affiliations
- Universidade Federal do Ceará (BR)
- Universidade Estadual de Londrina (BR)
- Translational Psychiatry Research Group and Department of Clinical Medicine Faculty of Medicine Federal University of Ceará Fortaleza CE Brazil
- University of Toronto (CA)
- Universidade Federal do Rio Grande do Sul (BR)
- National Health Service (GB)
- University of Padua (IT)
- University of Wisconsin–Madison (US)
- Augusta University (US)
- Corresponding author
- Carvalho, A. F.
- ORCID
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2017-01-25
- Volume
- 135
- Issue
- 5
- Pages
- 373-387
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2582903515
- Semantic Scholar
- c8ba0132ef96678f0e0a3d8e5530a8249cd924a3
- Cited by
- 1,443
- References
- 74
- Citations by year
- 2026: 134 · 2025: 178 · 2024: 177 · 2023: 195 · 2022: 195 · 2021: 159 · 2020: 146 · 2019: 127 · 2018: 93 · 2017: 38
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- major depressive disorder, cytokines, chemokines, interleukin-6, TNF-α, IL-10, interferon-gamma, soluble interleukin-2 receptor, MCP-1, soluble TNF receptor 2, interleukin-1 receptor antagonist, biomarkers, heterogeneity sources
- MeSH terms
- Major Depressive Disorder, Female, Humans, Male, Cytokines, Chemokines
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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