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Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis
Open accessAbstract
A large array of studies have investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. We searched Web of KnowledgeSM and Scopus® for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized.
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TL;DR
This systematic review and preliminary meta-analysis found no convincing evidence that peripheral oxytocin or vasopressin levels are reliable biomarkers across psychiatric disorders. The only Bonferroni-corrected significant difference was lower serum oxytocin in anorexia nervosa, amid high heterogeneity and methodological limitations.
Key findings
- Across 19 preliminary meta-analyses, none except serum OT in anorexia nervosa showed significant differences after correction: AN serum OT n=2, overall sample=71, Hedges’ g=−0.824, 95% CI −1.308 to −0.341, p corr=0.001.
- Several uncorrected signals did not survive Bonferroni correction: CSF OT in OCD g=0.599 (p unc=0.004, p corr=ns); CSF ADH in AN g=0.922 (p unc=0.008, p corr=ns); CSF ADH in OCD g=0.601 (p unc=0.003, p corr=ns); plasma ADH in psychosis g=−0.554 (p unc=0.008, p corr=ns); salivary OT in ASD g=−0.354 (p unc=0.046, p corr=ns).
- Heterogeneity was often substantial or considerable, e.g. plasma OT in ASD Q=64.613, I²=93.81, p<0.001; plasma ADH in psychosis Q=55.984, I²=82.14, p<0.001.
- In psychosis plasma ADH, extraction technique mattered: extracted studies n=6, overall sample=220, Hedges’ g=−1.099, 95% CI −1.617 to −0.581, p=0.001, Q=13.626, I²=63.31, p=0.018.
Methods
- Systematic search of Web of Knowledge and Scopus until March 1, 2015, plus manual reference search; English original articles with ICD/DSM psychiatric diagnosis, healthy comparison group, and peripheral OT/ADH in plasma/serum, saliva, urine, or CSF; MOOSE guidelines adopted.
- Sixty-four studies were included (final database 64 samples); 19 preliminary meta-analyses were performed; diagnoses with only one study available were not meta-analyzed.
- Hedges’ g effect sizes with random-effects models, Bonferroni correction (0.05 divided by number of meta-analyses), Q and I² heterogeneity, Duval and Tweedie trim-and-fill publication bias testing, sensitivity analyses, and adapted Newcastle-Ottawa Scale quality assessment.
Limitations
- The paper states subgroups were very small, studies were highly heterogeneous, and confounders were common: 38% of included studies reported lithium salts, 42/62 (68%) failed to control for alcohol intake, 70% (35/50) did not ascertain pregnancy, and only 18% of OT studies and no ADH studies analyzed menstrual cycle fluctuations; meta-regressions were not possible due numerical constraints.
- The paper states study quality was low: Newcastle-Ottawa Scale scores ranged from 1 to 7, median 4 out of 9, and meta-analytical estimates were preliminary with high uncertainty.
- Evident from the text: many meta-analyses pooled only 2 studies; urine and saliva ADH meta-analyses were not performed because insufficient data were retrieved; the effect of NOS scores on findings could not be directly assessed.
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Claims the paper makes
32 Own result · 25 Not checked yet · 24 Own method · 10 Own interpretation · 1 No basis given
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
“Psychosis (n ¼8, overall sample ¼691, Hedges' g¼ À0.005, 95% CI from À0.304 to 0.294, p unc ¼0.974, substantial between studies heterogeneity Q ¼24.923,I 2 ¼ 71.91, p¼ 0.001)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.2. OT levels in plasma/serum
plainn = 8- Asserted: passes — The authors put it forward as true.
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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
“BN (n¼ 2, overall sample¼86, Hedges' g¼ À0.219, 95% CI from À 0.755 to 0.318, p unc¼0.425, between studies heterogeneity non-significant)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.1. OT levels in CSF
plainn = 2- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“OT levels in saliva of ASD were not statistically different from those observed in healthy controls (n ¼2, overall sample ¼152, Hedges' g¼ À0.354, 95% CI from À 0.701 to À 0.006, p unc¼ 0.046, p corr ¼ ns, between studies heterogeneity non significant).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.3. OT levels in saliva
plainn = 2- Asserted: passes — The authors put it forward as true.
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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
“Patients with AN had lower serum OT levels than healthy comparisons (n¼ 2, overall sample ¼71, Hedges' g¼ À0.824, 95% CI from À 1.308 to À 0.341, p corr¼ 0.001, between studies heterogeneity non-significant).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.2. OT levels in plasma/serum
plainn = 2- Asserted: passes — The authors put it forward as true.
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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
“We found no differences between healthy comparisons and AN (n¼2, overall sample¼52, Hedges' g¼ À0.034, 95% CI from À 1.068 to 1.019, p unc¼0.950, between studies heterogeneity non-significant)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.1. OT levels in CSF
plainn = 2- Asserted: passes — The authors put it forward as true.
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- 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
“Psychosis (n¼3, overall sample¼147, Hedges' g¼0.287, 95% CI from À 0.330 to 0.903, p unc¼ 0.362, substantial between studies heterogeneity Q¼6.482,I 2 ¼69.14, p¼0.039)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.1. OT levels in CSF
plainn = 3- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“OCD (n¼ 2, overall sample¼99, Hedges' g¼0.599, 95% CI from 0.194 to 1.004, p unc¼0.004, p corr¼ns, between studies heterogeneity non-significant)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.1. OT levels in CSF
plainn = 2- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“MDD (n¼ 2, overall sample¼75, Hedges' g¼ À0.333, 95% CI from À0.781 to 0.114, p unc¼0.144, between studies heterogeneity non-significant)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.1. OT levels in CSF
plainn = 2- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“ASD (n ¼4, overall sample ¼404, Hedges' g¼ À0.576, 95% CI from À 1.442 to 0.291, p unc ¼0.193, considerable between studies heterogeneity Q¼ 64.613,I 2 ¼93.81, p o0.001)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.2. OT levels in plasma/serum
plainn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“BD (n¼ 3, overall sample ¼275, Hedges' g¼ 0.056, 95% CI from À 0.845 to 0.957, p unc ¼0.903, considerable between studies heterogeneity Q ¼20.796,I 2 ¼90.38, po 0.001)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.2. OT levels in plasma/serum
plainn = 3- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 16
- Probably not a substantial claim. 23
- 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
“Psychosis (n¼ 11, overall sample ¼630, Hedges' g¼ À0.554, 95% CI from À 0.966 to À 0.142, p unc ¼0.008, p corr ¼ns, considerable between studies heterogeneity Q ¼55.984,I 2 ¼ 82.14, p o0.001)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.3.2. ADH levels in plasma/serum
plainn = 11- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Average plasmatic levels within studies included in the present meta-analysis ranged from 0.64 pg/mL to 436.97 pg/mL for OT and from 0.66 pg/mL to 109.17 pg/mL for ADH”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.1. Reliability of assays
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Study quality scores ranged from 1 to 7 (median score was 4 out of 9 possible points).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.4. Quality assessment
plain- Asserted: passes — The authors put it forward as true.
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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
“Results were Bonferroni-corrected for multiple testing, by dividing 0.05 by the overall number of meta-analyses conducted.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.1. Effect size
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“Publication biases were tested with the Duval and Tweedie”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
What the sources say
- Not checked yetcites Duval and Tweedie, 2000 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“We conducted other sensitivity analyses to investigate the putative influence of several categorical moderators: assay technique, pregnancy, alcohol use and phase of the psychotic disorder.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“To further assess the robustness of the results, we performed sensitivity analyses by sequentially removing each study and re-running the analysis, when at least 5 studies were included (Higgins and Green, 2011).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
What the sources say
- Not checked yetcites Higgins and Green, 2011
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“To achieve high quality of reporting we adopted MOOSE guidelines (Stroup et al., 2000)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.1.1. Search strategies
What the sources say
- Not checked yetcites Stroup et al., 2000 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“As meta-analysis of observational studies is supposed to be characterized by significant heterogeneity, random effect models were used (Cooper et al., 2009).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
What the sources say
- Not checked yetcites Cooper et al., 2009
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“We performed an additional sub-group analysis dividing First Episode Psychosis (FEP) and chronic Psychosis vs healthy comparisons”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
plain- Asserted: passes — The authors put it forward as true.
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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
“Discrepancies were resolved through consensus with a third researcher [MR].”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.1.1. Search strategies
plain- Asserted: passes — The authors put it forward as true.
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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
“Heterogeneity among study point estimates was assessed using Q statistics (Paulson and Bazemore, 2010) and the proportion of the total variability in the effect size estimates evaluated with the I 2 index (Lipsey and Wilson, 2000).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.2.2. Heterogeneity, publication biases, sensitivity analysis
What the sources say
- Not checked yetcites Paulson and Bazemore, 2010 source
- Not checked yetcites Lipsey and Wilson, 2000
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“quality of reporting criterion (adapted Newcastle-Ottawa Scale http:// www.ohri.ca/programs/clinical_epidemiology/oxford.asp, see Supplementary material for detail)”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.1.4. Recorded variables
plain- Asserted: passes — The authors put it forward as true.
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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
“Meta-analyses were not performed as insufficient data were retrieved.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.4. OT levels in urine
plain- Asserted: passes — The authors put it forward as true.
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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
“A two-step literature search was conducted by two independent researchers [GR, AS].”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 2.1.1. Search strategies
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Both the commercially available immunoassays (RIA and EIA) have high heterogeneity and questionable validity (McCullough et al., 2013).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.1. Reliability of assays
What the sources say
- Not checked yetcites McCullough et al., 2013 source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“During pregnancy dramatic structural and functional changes occur in the OT system of the mother's brain (Hillerer et al., 2014;Rocchetti et al., 2014).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Again these results indicate that peripheral OT and ADH levels are not reliable biomarkers of BD/MDD.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.6. BD and MDD
hedged- Asserted: passes — The authors put it forward as true.
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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
“These findings are characterized by high heterogeneity, various methodological limitations, and poor quality.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 5. Conclusions
plain- Asserted: passes — The authors put it forward as true.
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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
“Several confounding factors might have had an impact on the results.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
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
“our results do not contradict the potential role of the two neuropeptides in mental disorders per se but do clearly suggest that peripheral levels do not reliably distinguish cases from controls.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4. Discussion
boosted- Asserted: passes — The authors put it forward as true.
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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
“Meta-analyses were not performed as insufficient data were retrieved.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.4. OT levels in urine
plain- Asserted: fails — The authors may not put it forward as true.
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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. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“There is considerable evidence of a role these two neuropeptides in various aspects of social behaviour.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.4. Psychosis
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“a body of literature that has demonstrated a role for these neuropeptides in functions which map on to common symptoms and behavioural deficits in psychosis and schizophrenia, in particular in the social cognition domain (MacDonald and MacDonald, 2010).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.4. Psychosis
What the sources say
- Not checked yetcites MacDonald and MacDonald, 2010 source
boostedcorrelational- 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 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
“As a consequence, our meta-analytical estimates are affected by high uncertainty and should be considered as a preliminary synthesis of the available literature.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
plaindirect- 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 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
“As the present analysis investigates between-group differences, not within-group effects our results do not contradict the potential role of these neuropeptides in the symptoms of psychosis per se.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.4. Psychosis
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
“No significant publication bias emerged.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.3.4. Publication bias and sensitivity analyses
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.
None of the sources cited for this claim have been checked yet.
In the paper
“As regard OT, preclinical studies in rats found that a systemic injection of lithium leads to a significant elevation of peripheral OT levels (Cui et al., 2001;You et al., 2001).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
What the sources say
plaindirect- 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
“With respect to other bodily fluids, such as saliva and urine, it has been demonstrated that the estimated levels are highly discrepant and weakly correlated to plasmatic levels (McCullough et al., 2013).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.1. Reliability of assays
What the sources say
- Not checked yetcites McCullough et al., 2013 source
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.
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
“they were included in some of the articles in the Psychosis subgroup (OT: 6 out of 11 (Goldman et al., 2008;Rubin et al., 2014Rubin et al., , 2013Rubin et al., , 2010;;Strauss et al., 2015;Walss-Bass et al., 2013)); ADH (4 out of 13 (Emsley et al., 1989;Ohsawa et al., 1993;Rubin et al., 2014Rubin et al., , 2013)))”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
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.
In the paper
“EIA performed without extraction yielded to values that were two orders of magnitude greater than those in extracted samples (Szeto et al., 2011) and without correlation, due to the presence of multiple adjunctive immunoreactive products besides oxytocin (Szeto et al., 2011).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.1. Reliability of assays
What the sources say
- Not checked yetcites Szeto et al., 2011 source
plaindirect- 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
“ADH is involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, which has been found to be overactive in BD (Cervantes et al., 2001;Daban et al., 2005) and MDD (Carroll et al., 1981;Dinan, 1994;Holsboer, 2000).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.6. BD and MDD
What the sources say
plaindirect- 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
“Moreover, high levels of oxytocinase secreted by the placenta might further contribute to the final serum/plasma OT levels (Nomura et al., 2005).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
What the sources say
- Not checked yetcites Nomura et al., 2005 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.
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
“The lack of significant association was secondary to high heterogeneity across individual studies, low quality and significant methodological limitations.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4. Discussion
plaindirect- 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
“Studies investigating plasma OT and ADH levels during the menstrual cycle in different species, including humans, found that these fluctuate across the ovarian cycle (Wathes and Swann, 1982).(Spruce et al., 1985).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
What the sources say
- Not checked yetcites Wathes and Swann, 1982
- Not checked yetcites Spruce et al., 1985 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
“Finally, only 18% of the studies investigating OT and none of those investigating ADH analyzed the fluctuations of OT levels across the menstrual cycle phases.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
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.
In the paper
“It is evident, as others have previously suggested (Christensen et al., 2014), that the two immunoassays are poorly correlated, thus preventing the comparison of results obtained by different research groups.”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.1. Reliability of assays
What the sources say
- Not checked yetcites Christensen et al., 2014 source
boosteddirect- 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.
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
“38% of the included studies reported that participants were taking lithium salts (eTable 3).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 4.8. Limitations
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
“According to the Bonferroni correction, each hypothesis has been tested at a significance level of 0.002 (CI unadjusted).”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 5. Conclusions
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Some, but not all, studies have shown reduced plasma oxytocin levels in children with autism spectrum disorder.6”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [6]
Experimental — accuracy not yet measuredIn the citing paper
“A recent systematic review has concluded that studies using ELISA on unextracted samples have produced no convincing evidence that peripheral vasopressin or oxytocin might be reliable biomarkers in psychiatric disorders 135.”
From Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers (2016) · cites this paper as [135]
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
“MDD (n ¼6, overall sample ¼423, Hedges' g¼ À0.341, 95% CI from À 0.078 to 0.759, p unc ¼0.111”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.3.2. ADH levels in plasma/serum
Reported -0.341 · recomputed 0.3405
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 oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 3.2.2. OT levels in plasma/serum
“ASD (n ¼4, overall sample ¼404, Hedges' g¼ À0.576”
§ Peripheral oxytocin and vasopressin: Biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis > 5. Conclusions
“(a) Taurines et al. (2014) | Germany | OT | Plasma | ASD | 36 | 19 | 10.7 | 13.6 | 0 | 0 |”
Citations
Cites
1 retracted
Gumley, A. I., Braehler, C., & MacBeth, A. M. (2014) · British Journal of Clinical Psychology · doi:10.1111/bjc.12041 · Cited by 34 · cited 3×
“Nevertheless, a recent meta-analysis examining the effects of OT on psychotic symptoms and social cognition found weak and inconsistent evidence, mainly because of methodological limitations, similarly as the ones observed by our current analysis (Gumley et al., 2014).”
RetractedCochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series
(2008) · doi:10.1002/9780470712184 · Cited by 25,048 · cited 3×
“To further assess the robustness of the results, we performed sensitivity analyses by sequentially removing each study and re-running the analysis, when at least 5 studies were included (Higgins and Green, 2011).”
InfluentialMeta-analysis of Observational Studies in Epidemiology<SUBTITLE>A Proposal for Reporting</SUBTITLE>
Stroup, D. F. (2000) · JAMA · doi:10.1001/jama.283.15.2008 · Cited by 20,623
Duval, S., & Tweedie, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00455.x · Cited by 14,099 · cited 2×
“Publication biases were tested with the Duval and Tweedie “trim and fill” method (Duval and Tweedie, 2000), when at least 3 studies were included.”
Method(2000) · Cited by 9,198
The Handbook of Research Synthesis and Meta-Analysis
(2019) · doi:10.7758/9781610448864 · Cited by 4,553 · cited 1×
“As meta-analysis of observational studies is supposed to be characterized by significant heterogeneity, random effect models were used (Cooper et al., 2009).”
MethodThe oxytocin receptor system: structure, function, and regulation
Gimpl, G., & Fahrenholz, F. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.629 · Cited by 3,089 · cited 1×
“They are released in systemic circulation through the posterior pituitary gland, where they act as hormones regulating a range of physiological functions (Gimpl and Fahrenholz, 2001; Leng et al., 2015).”
Carroll, B. J. (1981) · Archives of General Psychiatry · doi:10.1001/archpsyc.1981.01780260017001 · Cited by 2,243
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181 · cited 2×
“, 2005) and MDD (Carroll et al., 1981; Dinan, 1994; Holsboer, 2000).”
Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00465-7 · Cited by 2,091 · cited 2×
“…cues (Zak et al., 2005) and has an effect on emotion recognition/theory of mind (Domes et al., 2007; Guastella et al., 2010b), fearful face processing (Evans et al., 2010), social anxiety (Heinrichs et al., 2003), paranoia (Legros et al., 1992), and trust behaviour (Baumgartner et al., 2008).”
Cited by
Sorted by citations
The oxytocin receptor: from intracellular signaling to behavior
Jurek, B., & Neumann, I. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00031.2017 · Cited by 999
Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder
Sikich, L., Kolevzon, A., King, B. H., McDougle, C. J., Sanders, K. B., Kim, S.-J., Spanos, M., Chandrasekhar, T., Trelles, M. D. P., Rockhill, C. M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103583 · Cited by 298
Valstad, M., Alvares, G. A., Egknud, M., Matziorinis, A. M., Andreassen, O. A., Westlye, L. T., & Quintana, D. S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.017 · Cited by 277
Kim, J. Y., Son, M. J., Son, C. Y., Radua, J., Eisenhut, M., Gressier, F., Koyanagi, A., Carvalho, A. F., Stubbs, B., Solmi, M., et al. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30181-6 · Cited by 271
Self-citationLee, M. R., Scheidweiler, K. B., Diao, X. X., Akhlaghi, F., Cummins, A., Huestis, M. A., Leggio, L., & Averbeck, B. B. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.27 · Cited by 235
Metadata
- Authors
- Rutigliano, G., Rocchetti, M., Paloyelis, Y., Gilleen, J., Sardella, A., Cappucciati, M., Palombini, E., Dell’Osso, L., Caverzasi, E., Politi, P., McGuire, P., & Fusar-Poli, P.
- Affiliations
- University of Pisa (IT)
- King's College London (GB)
- University of Pavia (IT)
- ORCID
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 241
- Pages
- 207-220
- ISSN
- 0165-1781 (ISSN-L)
- OpenAlex
- W2346907797
- Semantic Scholar
- b0170825c65f1ff6ded651e1a64ce45a933e7750
- Cited by
- 149
- References
- 148
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 15 · 2022: 19 · 2021: 17 · 2020: 19 · 2019: 12 · 2018: 21 · 2017: 19 · 2016: 3
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Psychiatry Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- ESRC (ES/K009400/1)
- NARSAD
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- vasopressin, biomarkers, mental illness, saliva, plasma, serum, cerebrospinal fluid, urine, anorexia nervosa, methodological heterogeneity, study quality
- MeSH terms
- Mental Disorders, Humans, Oxytocin, Vasopressins, Reproducibility of Results, Biomarkers
About these checks
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.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-08 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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