Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies
Open accessAbstract
Over the last decade, oxytocin (OT) has received focus in numerous studies associating intranasal administration of this peptide with various aspects of human social behavior. These studies in humans are inspired by animal research, especially in rodents, showing that central manipulations of the OT system affect behavioral phenotypes related to social cognition, including parental behavior, social bonding, and individual recognition. Taken together, these studies in humans appear to provide compelling, but sometimes bewildering, evidence for the role of OT in influencing a vast array of complex social cognitive processes in humans. In this article, we investigate to what extent the human intranasal OT literature lends support to the hypothesis that intranasal OT consistently influences a wide spectrum of social behavior in humans. We do this by considering statistical features of studies within this field, including factors like statistical power, prestudy odds, and bias. Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects. Thus, the remarkable reports that intranasal OT influences a large number of human social behaviors should be viewed with healthy skepticism, and we make recommendations to improve the reliability of human OT studies in the future.
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Written from the paper’s full text.
TL;DR
This paper argues that human intranasal oxytocin (IN-OT) studies are generally underpowered and that many published positive findings likely do not represent true effects. The authors use meta-analytic effect sizes, power calculations, positive predictive value estimates, and a survey of 2014 IN-OT papers to recommend larger, more transparent, and better-replicated studies.
Key findings
- Across three published meta-analyses, the weighted mean effect size for healthy subjects was d=0.28 with median N=49, yielding average statistical power of 16%; clinical trials had median N=26, d=0.32, and power of 12%. To achieve 80% power, 352 healthy subjects or 310 clinical-trial participants would be needed.
- Even with the largest observed effect size (d=0.48) and largest sample size in the meta-analyses (N=112), power was no higher than 70%; sample sizes of 49 and 26 could reliably detect only large effects (d=0.81 to d=1.14) at 80% power.
- If pre-study odds R=0.10 and power is 16%, the positive predictive value (PPV) was no higher than 24%; with 10 independent tests and only one reported, PPV dropped to 17%.
- In 33 IN-OT papers from 2014, 29 (88%) reported at least one positive finding, but only 62 of 357 tested effects (17%) were significant; only 3 papers mentioned multiple-comparison correction, and the average number of tests was 11. Vole studies using central OT/vasopressin manipulation had a summarized effect size of d=0.76 (30 experiments, 668 individuals), though median n=22 and power=0.43.
Methods
- Reanalyzed data from three published meta-analyses of IN-OT effects, calculating sample-size-weighted average effect sizes for healthy subjects and clinical trials, then estimating power with G*Power and R simulations.
- Examined 33 behavioral IN-OT papers published in 2014, recording positive findings, total tested effects, multiple-comparison correction, and number of tests, as described in supplemental information.
- Estimated effect sizes from 30 independent vole partner-preference experiments (668 individuals total) to compare central OT/vasopressin manipulation with intranasal administration.
Limitations
- The authors state that the true pre-study odds (R) for IN-OT studies cannot be determined with much certainty, and their PPV estimates assume no influence of bias, so actual PPV could be considerably lower.
- They note that publication-bias tests in the IN-OT meta-analyses gave mixed results and may be unreliable because small sample sizes provide insufficient power and sample-size variability; they also state they cannot assess the independence of tests in the 2014 survey.
- The vole effect-size analysis was underpowered (median n=22, 1−β=0.43), and the larger autism effect size (d=0.57) came from only four studies and should be interpreted cautiously. Evident from the text: the 2014 paper survey is treated as representative only conditionally, and the field-wide conclusions depend on that assumption.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
42 of 62 cited sources checked · 26 supported · 1 flagged · accuracy not yet measured
- Premisecitation§ Introduction
These meta-analyses yielded summarized effect sizes ranging from d=0.21 to d=0.48.
“These studies yielded summarized effect sizes ranging from d=0.21 to d=0.48.”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [9] Van IJzendoorn, 2012, A sniff of trust: Meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group, Psychoneuroendocrinology source
- cites [10] Shahrestani, 2013, The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: A meta-analysis, Neuropsychopharmacology source
The Moderation by Emotion Type section reports an effect size of Hedges’ g=0.210 for angry faces, close to the stated lower bound. It does not establish 0.48 as the upper bound: the same section reports g=0.591 for fearful faces, and the paper reports Hedges’ g rather than Cohen’s d (Statistical Analyses). No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
The Meta-analysis section reports a combined effect size of d=0.32 for 19 clinical experiments and d=0.57 for the autism-spectrum subset. The latter exceeds the claimed upper bound of d=0.48; the reported range is therefore not supported by this paper. Page numbers are not available in our copy. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
- Premisecitation§ Introduction
Three meta-analyses of the effects of intranasal oxytocin on human behavior have been published to date.
“To date three meta-analyses of the effects of IN-OT on human behavior have been published.”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [9] Van IJzendoorn, 2012, A sniff of trust: Meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group, Psychoneuroendocrinology source
The Method section (page unavailable) says this paper reports three meta-analyses of intranasal oxytocin’s effects on face recognition, in-group trust, and out-group trust. It does not establish that these were the only three meta-analyses published to date; the three analyses are reported in this one paper. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [10] Shahrestani, 2013, The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: A meta-analysis, Neuropsychopharmacology source
The title and Criteria for Considering Studies for this Review identify this paper as a meta-analysis of intranasal oxytocin’s effects on human emotion recognition. The Introduction also discusses another oxytocin meta-analysis. Our copy does not establish that exactly three meta-analyses of intranasal oxytocin’s effects on human behavior had been published to date. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
- Interpretationcitation§ Introduction
The pre-study odds of studies investigating the effect of intranasal oxytocin are low, primarily due to limitations in deep brain penetration of oxytocin when administered intranasally.
“Although the idea that manipulating OT in humans could influence social behavior is supported by rigorous animal research, we argue that the pre-study odds of studies investigating the effect of IN-OT still would be low, primarily due to limitations in deep brain penetration of OT when administered intranasally (2, 19).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [2] Churchland, 2012, Modulating social behavior with oxytocin: How does it work? What does it mean?, Horm Behav source
Section 2B questions whether intranasal oxytocin reaches brain receptor sites in sufficient amounts and notes its poor penetration across the blood–brain barrier. It does not establish that intranasal delivery has limited deep-brain penetration or assess the pre-study odds of such studies; those are stronger claims than the paper makes. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [19] Leng, 2016, Intranasal oxytocin: Myths and delusions, Biol Psychiatry source
- Premisecitation§ Introduction
Adopting a relatively conservative alpha level of 5% does not largely accomplish avoiding false positives.
“As Ioannidis (16) showed by statistical modeling this is not the case.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [16] Ioannidis, 2005, Why most published research findings are false, PLoS Med source
- Premisecitation§ Introduction
Publication bias tests might be problematic for intranasal oxytocin studies due to small sample sizes resulting in insufficient statistical power and sample size variability for the tests to yield reliable and significant results.
“However, publication bias tests might be problematic for IN-OT studies due to small sample sizes resulting in insufficient statistical power and sample size variability for the tests to yield reliable and significant results (26).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [26] Ioannidis, 2007, The appropriateness of asymmetry tests for publication bias in meta-analyses: A large survey, CMAJ source
The Abstract says asymmetry tests have low power when a meta-analysis includes few studies and are not meaningful when studies have similar precision. The Interpretation likewise identifies too few studies and too little difference between study sizes as problems. The paper does not examine intranasal oxytocin studies or establish that their sample sizes have these characteristics; it also distinguishes few studies from small samples within studies. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation§ Introduction
Melanocortin receptor agonists facilitate OT-dependent partner preferences in prairie voles.
“facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40)”
Quote in the paperNot a substantial claim4 of 4 sources checked- cites [35] Modi, 2012, The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies, Horm Behav source
In “Enhancing endogenous OT release” (page unavailable), the paper says preliminary, unpublished studies suggest a melanocortin receptor agonist promotes partner preference in prairie voles. It proposes that MC4R agonists increase central OT release, drawing on evidence from rats, but does not establish that the vole partner-preference effect is OT-dependent. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [37] Modi, 2015, Melanocortin receptor agonists facilitate oxytocin-dependent partner preference formation in the Prairie Vole, Neuropsychopharmacology source
- cites [39] Barrett, 2015, The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles, Transl Psychiatry source
- cites [40] Barrett, 2014, Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner, Neuropharmacology source
- Findingown data§ Introduction
If the value of pre-study odds (R) for intranasal oxytocin studies is approximately 0.10, the PPV is no higher than 24%, given a statistical power of 16%.
“If the value of R for IN-OT studies is approximately 0.10, comparable to what has suggested for experimental psychology (21) and exploratory epidemiology (16), the PPV is no higher than 24%, given a statistical power of 16%.”
Quote in the paperSubstantial claim1 of 2 sources checked - Premisecitation§ Introduction
Publication bias is more likely to affect low powered studies.
“and there are also reasons to believe that publication bias is more likely to affect low powered studies (25).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Dwan, 2008, Systematic review of the empirical evidence of study publication bias and outcome reporting bias, PloS One source
The Results (Publication and trial findings; page unavailable) report that studies with statistically significant results were more likely to be published, which provides a reason for the citing sentence's concern. But the review does not compare publication bias by statistical power or state that low-powered studies are more affected; its mentions of power concern discrepancies in reported power calculations. (LLM, conf=0.78)
Experimental — accuracy not yet measured
- Premisecitation§ Introduction
The more popular or trendy a scientific field is, the less likely it is to generate true findings.
“In addition, it has been shown that the more popular or “trendy” a scientific field is the less likely it is to generate true findings (16) and the extent to which a study overestimates true effects is positively correlated with the impact factor of a journal (30).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [16] Ioannidis, 2005, Why most published research findings are false, PLoS Med source
- Premisecitation§ Introduction
The behavioral effects of OT are evolutionary conserved.
“we believe the behavioral effects of OT are indeed evolutionary conserved (6, 32)”
Quote in the paperNot a substantial claim1 of 2 sources checked - Premisecitation§ Introduction
Most papers in behavioral intranasal oxytocin studies report positive findings.
“When reading the literature on behavioral IN-OT studies in humans it is obvious that most papers report positive findings, which is in line with a study by Fanelli showing that more than 80% of scientific publications in various sciences report positive results (22).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [22] Fanelli, 2010, “Positive” results increase down the Hierarchy of the Sciences, PloS One source
- Premisecitation§ Introduction
Melanocortin receptor agonists potentiate central OT release in the brain.
“melanocortin receptor agonists potentiate central OT release in the brain (37, 38)”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [37] Modi, 2015, Melanocortin receptor agonists facilitate oxytocin-dependent partner preference formation in the Prairie Vole, Neuropsychopharmacology source
- cites [38] Sabatier, 2003, Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis, J Neurosci source
- Premisecitation§ Introduction
OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates.
“OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43)”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [6] Young, 2015, Oxytocin, social cognition and psychiatry, Neuropsychopharmacology source
- cites [42] Freeman, 2014, The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta), Psychoneuroendocrinology source
The Discussion section on the nucleus basalis of Meynert and pedunculopontine tegmental nucleus reports OXTR expression in cholinergic regions linked to visual attention in rhesus macaques. The trapezoid-body section detects OXTR in an auditory relay, but calls its proposed auditory role speculative; it does not establish that receptors are concentrated in cholinergic regions regulating auditory attention. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [43] Freeman, 2014, Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus), Neuroscience source
Discussion §4.2 reports OXTR in the nucleus basalis of Meynert across several primates and identifies it as important for visual attention; §4.5 says OXTR is consistently concentrated in visual-processing and attention areas. The paper does not establish that OXTR is concentrated in cholinergic regions regulating auditory attention. Its mention of audition in §4.5 concerns a broader evolutionary shift in social-information processing, not auditory attention. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Findingreasoning§ Introduction
For the average effect size in clinical trials (d=0.32), 310 individuals are needed to achieve 80% power.
“Similarly, for the average effect size in clinical trials (d=0.32), 310 individuals are needed to achieve 80% power.”
Quote in the paperSubstantial claim - Findingown data§ Abstract
Intranasal oxytocin studies are generally underpowered.
“Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects.”
- Also stated in: § Introduction · plain
“As seen in Figure 1, IN-OT studies in humans are underpowered.”
- Also stated in: § Introduction · boosted
“Our analyses demonstrate that IN-OT studies are generally considerably underpowered.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Findingreasoning§ Introduction
Intranasal oxytocin studies considerably overestimate the true effect size.
“Clearly, IN-OT studies considerably overestimate the true effect size.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The median sample size for the individual studies in these meta-analyses was 49 individuals.
“The median sample size for the individual studies in these meta-analyses was 49 individuals.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The average study investigating the effect of intranasal oxytocin in healthy subjects has a statistical power of 16%.
“Our results indicate that the average study investigating the effect of IN-OT in healthy subjects has a statistical power of 16%.”
Quote in the paperSubstantial claim - Findingreasoning§ Introduction
To achieve 80% power given the summarized effect size of 0.28 for healthy subjects, a sample size of 352 individuals would be needed.
“In order to achieve 80% power given the summarized effect size of 0.28 for healthy subjects, a sample size of 352 individuals would be needed.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
For clinical trials, the statistical power is 12%.
“For clinical trials the median sample size is 26 individuals and the effect size is d=0.32, resulting in a statistical power of only 12%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
Even with the largest observed effect size (0.48) and largest observed sample size (N=112), the statistical power is no higher than 70%.
“Even in the situation in which the true effect size is 0.48 (the largest observed) and the sample size also is the largest observed within studies included in the meta-analyses (i.e., N = 112) the statistical power is no higher than 70%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
For all sample sizes and effect sizes in the meta-analyses, the power is lower than 80%.
“For all sample sizes and effect sizes the power is lower than 80% (often considered the standard for minimal adequate statistical power).”
Quote in the paperSubstantial claim - Findingreasoning§ Introduction
Studies within the median sample size range can only reliably detect large effect sizes (d=0.81 to d=1.14) with 80% power.
“Studies within this sample size range can only reliably detect large effect sizes (d=0.81 to d=1.14) with 80% power.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
For clinical trials, the effect size is d=0.32.
“For clinical trials the median sample size is 26 individuals and the effect size is d=0.32, resulting in a statistical power of only 12%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The mean effect size for healthy subjects included in the meta-analyses, weighted by sample size, is d=0.28.
“This resulted in a mean effect size of d=0.28.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
For clinical trials, the median sample size is 26 individuals.
“For clinical trials the median sample size is 26 individuals and the effect size is d=0.32, resulting in a statistical power of only 12%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
Twenty-nine out of the investigated 33 papers (88%) reported at least one positive finding (uncorrected p-value below 0.05).
“Twenty-nine out of the investigated 33 papers (88%) reported at least one positive finding (uncorrected p-value below 0.05).”
Quote in the paperSubstantial claim - Findingreasoning§ Introduction
If data from 10 independent tests are collected and only reported for one of these, with statistical power 16% and R-value 0.10, then the PPV goes down from 24% to 17%.
“For example, if data from 10 independent tests are collected and only reported for one of these, the statistical power is 16% for all tests and the R-value is 0.10, then the PPV goes down from 24% to 17%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The negative influence of decreasing pre-study odds on PPV is strong when the power is as low as the average power of behavioral studies of intranasal oxytocin in humans.
“The negative influence of decreasing pre-study odds on PPV is strong in the case when the power is as low as the average power of behavioral studies of IN-OT in humans.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The average number of tests performed in the 33 studies is 11.
“The average number of tests performed in the 33 studies is 11, but it should be mentioned that we have no way to assess to what extent these tests are independent.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
Sample sizes of hundreds of individuals are necessary to produce reliable data given these effect size estimates.
“Our calculations show that sample sizes of hundreds of individuals are necessary to produce reliable data given these effect size estimates.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
Low statistical power has a large negative impact on positive predictive value (PPV).
“Importantly, low statistical power has a large negative impact on PPV.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
When pre-study odds (R) are low, the probability of reported positive findings being true is low.
“As shown in Figure 3 when R is low the probability of reported positive findings being true is low.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
If the effect size is d=0.28 and the sample size is 49 individuals, 8 repeated trials (4 in each drug condition) can be enough to gain 80% power even when the correlation between trials is as low as 20%.
“Our simulations show that if the effect size is d=0.28 and the sample size is 49 individuals, 8 repeated trials (4 in each drug condition) can be enough to gain 80% power even when the correlation between trials is as low as 20%.”
Quote in the paperSubstantial claim - Findingown data§ Introduction
The vole studies are underpowered considering the small samples used (median n = 22, 1−β = 0.43).
“Although these vole studies are underpowered considering the small samples used (median n = 22, 1−β = 0.43)”
Quote in the paperNot a substantial claim - Findingown data§ Introduction
17% (62 out of 357) of all tested effects were statistically significant when calculating the proportion of positive findings over the total amount of tests across all studies.
“However, 17% (62 out of 357) of all tested effects were statistically significant when calculating the proportion of positive findings over the total amount of tests across all studies.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Abstract
There is a high probability that most published intranasal oxytocin findings do not represent true effects.
“Our conclusion is that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intranasal OT findings do not represent true effects.”
- Also stated in: § Introduction · hedged
“it is possible that most published “positive” findings within the field actually are false positives, and thus do not represent true effects.”
- Also stated in: § Introduction · hedged
“Taken together this suggests that most of the reported “positive” findings regarding how OT affects human behavior are likely to be false positives.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · hedged
- Premisecitation§ Introduction
In situations when an underpowered study detects a true effect, the estimate of this effect size is likely to be highly exaggerated (winner's curse).
“Further, in situations when an underpowered study detects a true effect, the estimate of this effect size is likely to be highly exaggerated, a phenomenon often referred to as the “winner’s curse” (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Ioannidis, 2008, Why most discovered true associations are inflated, Epidemiology source
- Interpretationreasoning§ Introduction
Replication attempts of true positive findings would fail up to 88% of the time.
“In other words, replication attempts of true positive findings would fail up to 88% of the time.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Introduction
If statistical power is only 12% to 16%, the false negative rate is between 84% and 88%.
“If the statistical power is only 12% to 16%, this implies that the false negative rate is between 84% and 88%.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Introduction
In the intranasal oxytocin field, this translates into a wide spectrum of investigated phenotypes beyond what can reasonably be predicted based on prior animal research.
“Regarding the IN-OT field this seems to translate into a wide spectrum of investigated phenotypes beyond what can reasonably be predicted based on prior animal research.”
Quote in the paperNot a substantial claim - Premisecitation§ Introduction
Type I errors are easily inflated when researchers employ undisclosed analytic flexibility regarding choice of statistical model, definition of variables, and rationale for exclusion of outliers.
“As shown by Simmons et al. (2011), Type I errors are easily inflated when researchers allow themselves to employ undisclosed analytic flexibility regarding choice of statistical model, definition of variables, and the rationale for exclusion of outliers (27).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Simmons, 2011, False-positive psychology: Undisclosed flexibility in data collection and analysis allows presenting anything as significant, Psychol Sci source
- Interpretationown data§ Introduction
Gathering repeated measures from individuals on the same behavioral task can be an efficient way to increase statistical power, thus avoiding the need to recruit as many participants.
“Further, gathering repeated measures from individuals on the same behavioral task can be an efficient way to increase statistical power, thus avoiding the need to recruit as many participants.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Introduction
This leads to a high probability that the reported effects of intranasal oxytocin are overestimated.
“This leads to a high probability that the reported effects of IN-OT are overestimated.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Conceptual replications are not necessarily more effective than direct replications at assessing the validity and generality of previous studies.
“Although it is often argued that conceptual replications assess both the validity and generality of previous studies, and therefore should be considered more effective than direct replications, this is not necessarily true (21).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Pashler, 2012, Is the replicability crisis overblown? Three arguments examined, Perspect Psychol Sci source
- Interpretationcitation§ Introduction
If about 10% of all postulated hypotheses are correct, in the absence of bias, only about 2% of the investigated effects would turn out to be statistically significant.
“If about 10% of all postulated hypotheses are correct, similar to what is expected for experimental psychology in general (21), we would expect, in the absence of bias, that only about 2% of the investigated effects would turn out to be statistically significant.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Pashler, 2012, Is the replicability crisis overblown? Three arguments examined, Perspect Psychol Sci source
- Interpretationreasoning§ Introduction
The field of behavioral intranasal oxytocin studies in humans is prone to several types of bias.
“Taken together we think that it is fair to say that the field of behavioral IN-OT studies in humans is prone to several types of bias.”
Quote in the paperSubstantial claim - Interpretationown data§ Introduction
The vole study results indicate that larger effect sizes can be achieved by more efficient routes of administration.
“these results indicate that larger effect sizes can be achieved by more efficient routes of administration.”
Quote in the paperSubstantial claim- Rests on an assumption: The vole partner preference test results with central OT/vasopressin manipulation are informative about human IN-OT effect sizes.
- Interpretationreasoning§ Introduction
The combination of low power and low pre-study odds results in low PPV estimates.
“The combination of low power and low pre-study odds results in low PPV estimates.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Introduction
If many outcome variables are investigated and selective reporting is present, or correction for multiple testing is not adopted, the likelihood of any study finding statistically significant results will be determined by the number of dependent variables rather than an actual underlying effect.
“If many outcome variables are investigated and selective reporting is present, or correction for multiple testing is not adopted, the likelihood of any study finding statistically significant results will be determined by the number of dependent variables rather than an actual underlying effect.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Introduction
It is very unlikely that all hypotheses about how intranasal oxytocin affects human behavior are true.
“But it seems very unlikely that all hypotheses about how IN-OT affects human behavior are true, as described in the previous section.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Introduction
Considering the low statistical power within the field of intranasal oxytocin, approximately 80% of all attempts to detect a true effect would fail.
“Considering the low statistical power within the field of IN-OT we would expect that approximately 80% of all attempts to detect a true effect would fail.”
Quote in the paperNot a substantial claim - Interpretationcitation§ Introduction
In addition to publication bias, the excess of statistically significant findings may be explained partly by the use of other questionable research practices.
“In addition to publication bias, the excess of statistically significant findings may be explained partly by the use of other questionable research practices.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
The extent to which a study overestimates true effects is positively correlated with the impact factor of a journal.
“and the extent to which a study overestimates true effects is positively correlated with the impact factor of a journal (30).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [30] Munafo, 2009, Bias in genetic association studies and impact factor, Mol Psychiatry source
- Interpretationreasoning§ Introduction
A significant amount of unpublished negative or inconclusive results (publication bias/file-drawer effect) may explain the excess of positive findings.
“An alternative, perhaps more plausible, explanation is that there could be a significant amount of unpublished negative or inconclusive results, a phenomenon referred to as the “file-drawer effect” or publication bias (23).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Rosenthal, 1979, The file drawer problem and tolerance for null results, Psychol Bull source
- Interpretationcitation§ Introduction
The localization of OT receptors in nonhuman primates is consistent with the putative localization of OT receptors in human brain.
“consistent with the putative localization of OT receptors in human brain (44)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Loup, 1991, Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study, Brain Res source
- Classified as probably not a substantial claim. 25
- May combine two claims. 16
- The quote only partly states this claim. 1
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ IntroductionVan IJzendoorn and Bakersmans-Kranenburg investigated the effect of intranasal oxytocin on facial emotion recognition, trust to in-group, and trust to out-group.
“Van IJzendoorn and Bakersmans-Kranenburg investigated the effect of IN-OT on facial emotion recognition (13 effect sizes, total N = 408), trust to in-group (8 effect sizes, total N = 317) and trust to out-group (10 effect sizes, total N = 505) (9).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [9] Van IJzendoorn, 2012, A sniff of trust: Meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group, Psychoneuroendocrinology source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionOxytocin has a role in regulating complex social behavior, including parental care, social bonding and social cognition in general.
“More recently, attention has turned to its role in regulating complex social behavior, including parental care, social bonding and social cognition in general (1–6).”
Quote in the paperNot a substantial claim4 of 6 sources checked- cites [1] Bartz, 2011, Social effects of oxytocin in humans: Context and person matter, Trends Cogn Sci source
- cites [2] Churchland, 2012, Modulating social behavior with oxytocin: How does it work? What does it mean?, Horm Behav source
- cites [3] Evans, 2014, Intranasal oxytocin effects on social cognition: A critique, Brain Res source
- cites [4] Guastella, 2013, Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research, Psychoneuroendocrinology source
- cites [5] Ross, 2009, Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior, Front Neuroendocrin source
- cites [6] Young, 2015, Oxytocin, social cognition and psychiatry, Neuropsychopharmacology source
May combine two claims.
Premisecitation§ IntroductionThe pre-study odds (R) for phase III clinical trials is approximately 1, meaning that in about 50% of the time the drugs that make it to these trials are more effective than the current gold standard treatment.
“Data suggest that the R for phase III clinical trials is approximately 1, meaning that in about 50% of the time the drugs that make it to these trials are more effective than the current “gold standard” treatment (18).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [18] Djulbegovic, 2013, Medical research: Trial unpredictability yields predictable therapy gains, Nature source
Classified as probably not a substantial claim.
Premisecitation§ IntroductionBakermans-Kranenburg and Van IJzendoorn studied the effect of intranasal oxytocin in clinical trials.
“Bakermans-Kranenburg and Van IJzendoorn studied the effect of IN-OT in clinical trials (19 effect sizes, total N=304)(11).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
Classified as probably not a substantial claim.
Premisecitation§ IntroductionIntranasal oxytocin administration influences various aspects of human social behavior.
“Much of the excitement regarding OT over the past decade has been driven by a remarkable proliferation of research suggesting that intranasal OT (IN-OT) administration influences various aspects of human social behavior (7).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Young, 2012, Editorial comment: Oxytocin, vasopressin and social behavior, Horm Behav source
Classified as probably not a substantial claim.
Premisecitation§ IntroductionShahrestani et al. conducted a meta-analysis of studies examining the effect of oxytocin on recognition of basic emotions.
“Shahrestani et al. conducted a meta-analysis of studies examining the effect of OT on recognition of basic emotions (7 effect sizes, total N = 381)(10).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] Shahrestani, 2013, The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: A meta-analysis, Neuropsychopharmacology source
The Introduction says the meta-analysis examined oxytocin’s effect on recognition of basic facial emotions, and Study Characteristics reports seven independent studies comprising 381 participants. The citing sentence calls these “7 effect sizes,” but the source says seven studies; its Results report a heterogeneity statistic with 13 degrees of freedom, so the effect-size count is not supported. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionThe average power of studies in neuroscience in general is 21%.
“but not very different from studies in neuroscience in general (average power = 21%) (14).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [14] Button, 2013, Power failure: Why small sample size undermines the reliability of neuroscience, Nat Rev Neurosci source
The Results section reports 21% as the median statistical power across the studies analyzed, not the arithmetic average. The paper discusses this estimate in relation to neuroscience generally, but the cited figure is mislabeled as an average. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
Premisecitation§ IntroductionMore than 80% of scientific publications in various sciences report positive results.
“which is in line with a study by Fanelli showing that more than 80% of scientific publications in various sciences report positive results (22).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [22] Fanelli, 2010, “Positive” results increase down the Hierarchy of the Sciences, PloS One source
The Results report that 2045 of 2434 papers (84%) across 20 disciplines gave positive or partial support for a tested hypothesis. But the study included only papers that explicitly tested a hypothesis, and the Discussion notes its focus on English-language scientific journals; it does not establish that more than 80% of scientific publications generally report positive results. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionMelanocortin receptor agonists mimic the prosocial effects of OT in a mouse model of autism.
“mimic the prosocial effects of OT in a mouse model of autism (41)”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [41] Penagarikano, 2015, Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism, Sci Transl Med source
May combine two claims.
Premisecitation§ IntroductionThe meta-analyses mentioned in this paper all tested for evidence of publication bias in the intranasal oxytocin literature, with mixed results.
“The meta-analyses mentioned in this paper all tested for evidence of publication bias in the IN-OT literature, with mixed results (9–11).”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [9] Van IJzendoorn, 2012, A sniff of trust: Meta-analysis of the effects of intranasal oxytocin administration on face recognition, trust to in-group, and trust to out-group, Psychoneuroendocrinology source
- cites [10] Shahrestani, 2013, The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: A meta-analysis, Neuropsychopharmacology source
- cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
The Meta-analysis section reports using trim-and-fill to assess potential publication bias in the clinical-trial meta-analysis and finding no bias against small studies with small effects. The Meta-analytic evidence section also describes analyses of healthy participants, but does not report publication-bias tests for them. This source therefore supports that a bias test was conducted, not that all the meta-analyses mentioned were tested or that their bias results were mixed. (LLM, conf=0.83)
Experimental — accuracy not yet measured
May combine two claims.
Study design and conductcitation§ IntroductionOnly four studies of autism were included in the meta-analysis and should therefore be interpreted cautiously.
“Only four studies of autism were included in the analysis and should therefore be interpreted cautiously.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ IntroductionThese alternate means of manipulating the OT system, if used in humans, could potentially increase the effect size to levels similar to central injections of OT.
“These alternate means of manipulating the OT system, if used in humans, could potentially increase the effect size to levels similar to central injections of OT (36).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [36] Young, 2015, Can oxytocin treat autism?, Science source
In “Can oxytocin treat autism?” (page unavailable), Young suggests that alternative approaches to the oxytocin system may overcome limitations of current therapies and improve social cognition; a DREADD approach might one day be feasible in humans. The paper does not discuss effect sizes or predict effects comparable to central oxytocin injections. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
Interpretationcitation§ IntroductionUnderstanding the precise neural and cognitive effects of OT manipulation on the processing of social information can be used to increase the efficacy of OT-based therapies to improve social function in psychiatric disorders.
“Understanding the precise neural and cognitive effects of OT manipulation on the processing of social information can be used to increase the efficacy of OT-based therapies to improve social function in psychiatric disorders (36).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [36] Young, 2015, Can oxytocin treat autism?, Science source
May combine two claims.
Premisecitation§ IntroductionIn the meta-analysis by Bakermans-Kranenburg and Van IJzendoorn, IN-OT seems to have the largest effect size in individuals with autism, with d=0.57 for autism compared to d=0.32 for all clinical studies.
“Finally, in the meta-analysis by Bakermans-Kranenburg and Van IJzendoorn (11) IN-OT seems to have the largest effect size in individuals with autism. Only four studies of autism were included in the analysis and should therefore be interpreted cautiously. However, the larger effect size for autism (d=0.57) compared to all clinical studies (d=0.32)”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [11] Bakermans-Kranenburg, 2013, Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy, Transl Psychiatry source
The Meta-analysis reports d=0.57 for four studies grouped under autism spectrum disorder, compared with d=0.32 across 19 clinical experiments, and cautions that the syndrome-specific evidence is small. But the autism grouping includes Prader–Willi syndrome, and the paper’s Autism spectrum disorders section describes an intravenous OT trial; these figures are not presented as estimates exclusively for intranasal OT in individuals with autism. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
Findingown data§ IntroductionIn cases where the sample size is below 40 individuals the inflation is very large, but even when N=100, the overestimation of the effect is by no means negligible.
“In cases where the sample size is below 40 individuals the inflation is very large, but even when N=100, the overestimation of the effect is by no means negligible.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Findingnone given§ IntroductionIN-OT studies are underpowered.
“since the IN-OT studies are underpowered”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ IntroductionOut of the 33 intranasal oxytocin papers investigated, only 3 mention that any correction for multiple comparisons was performed, and in these cases it is unclear how corrections were applied.
“For example, out of the 33 IN-OT papers we investigated, only 3 mention that any correction for multiple comparisons was performed, and in these cases it is unclear how corrections were applied.”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown data§ IntroductionEffect sizes were estimated for 30 independent vole experiments comprising 668 individuals in total, weighted by sample size, yielding a summarized effect size of d = 0.76 for behavioral effects of centrally manipulating the OT/vasopressin systems.
“Effect sizes were estimated for 30 independent experiments comprising 668 individuals in total, weighted by the sample size of the individual experiments. This yielded a summarized effect size of d = 0.76.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionLarge-scale phase III clinical trials represent the case when the value of pre-study odds (R) will be the highest.
“Button et al. have argued that large-scale phase III clinical trials represent the case when the value of R will be the highest (17).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Button, 2013, Empirical evidence for low reproducibility indicates low pre-study odds, Nat Rev Neurosci source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ IntroductionPower calculations were verified using simulation in R, which yielded very similar results compared to G*Power.
“For verification, power calculations were also performed using simulation in R (3.1.1) (13) (Figure 1), and yielded very similar results compared to G*Power.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Core Team, 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.
Premisecitation§ IntroductionThe publication culture promotes novel, and often surprising, findings and this motivates researchers to postulate improbable hypotheses.
“Also, the publication culture promotes novel, and often surprising, findings and this will motivate researchers to postulate improbable hypotheses (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Bakker, 2012, The rules of the game called psychological science, Perspect Psychol Sci source
May combine two claims.
Premisecitation§ IntroductionUse of multiple analyses on the same data set and selective reports of statistical methods used, or insufficient correction for multiple comparisons, can cause inflation in effects.
“Use of multiple analyses on the same data set and selective reports of statistical methods used, or insufficient correction for multiple comparisons, can cause inflation in effects (29).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] Nieuwenhuis, 2011, Erroneous analyses of interactions in neuroscience: A problem of significance, Nat Neurosci source
May combine two claims.
Interpretationreasoning§ IntroductionThe problem with IN-OT research is not the hypothesis that OT could be a modulator of human behavior, but the certainty that any particular reported finding represents a true effect.
“The problem here is not the underlying hypothesis that OT could be a modulator of human behavior, it is in the certainty in which we can have faith that any particular reported finding represents a true effect.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ IntroductionReplicating findings in samples of the same size as the original underpowered IN-OT study will lead to many unsuccessful replication attempts due to insufficient power, undermining the original true finding.
“Also, since the IN-OT studies are underpowered it does not make sense to try to replicate findings in samples of the same size as the original study. This will lead to many unsuccessful replication attempts due to insufficient power, undermining the original true finding.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone given§ IntroductionUnderpowered studies are prone to other types of biases, such as the use of questionable research practices.
“Also, underpowered studies are prone to other types of biases, such as the use of questionable research practices.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionSuch questionable practices are common in psychology and likely pervasive in other disciplines.
“Such questionable practices are common in psychology (28), and likely pervasive in other disciplines as well.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] John, 2012, Measuring the prevalence of questionable research practices with incentives for truth telling, Psychol Sci source
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone given§ IntroductionThe results of the calculations for human IN-OT studies would not differ for other species given intranasal OT, like non-human primates, as long as the dose is adjusted for body weight.
“Our calculations are focused on human studies, but we see no reason to expect that these results would differ for other species given OT intranasally, like non-human primates, as long as the dose is adjusted for body weight.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S4 (based).
Interpretationnone given§ IntroductionChanges in research practices could increase the trustworthiness of the data.
“Changes in research practices could increase the trustworthiness of the data.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone given§ IntroductionWithin the field of behavioral intranasal oxytocin studies in humans, there are several other examples of questionable practices including unjustified use of one-tailed tests and unexplained exclusion of outliers.
“Within the field of behavioral IN-OT studies in humans, there are several other examples of questionable practices including the use of statistical methods, such as unjustified use of one-tailed tests and unexplained exclusion of outliers.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone given§ IntroductionThe estimated PPV values assume no influence of bias, meaning that the actual PPV values could be considerably lower.
“However discouraging these estimated values might seem they assume no influence of bias, meaning that the actual PPV values could be considerably lower.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown data§ IntroductionReporting bias and multiple comparisons issues seem to be problems for studies of intranasal oxytocin.
“Reporting bias and multiple comparisons issues seem to be problems for studies of IN-OT.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).
Interpretationnone given§ IntroductionIncreased confidence in data from clinical trials involving IN-OT would entice funding agencies and pharmaceutical companies to support more research in the field.
“Increased confidence in data from clinical trials involving IN-OT would entice funding agencies and pharmaceutical companies to support more research in the field.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Interpretationreasoning§ IntroductionIf the 17% figure represents the true proportion of successful experiments, this would mean that almost all investigated hypotheses within these studies are true.
“If this number represents the true proportion of successful experiments, this would mean that almost all investigated hypotheses within these studies are true.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Premisereasoning§ IntroductionWhen a research field is, to a large degree, exploratory, the pre-study odds decrease.
“When a research field is, to a large degree, exploratory, the pre-study odds decrease.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).
Interpretationnone given§ IntroductionCentral injections will never be a common way to administer drugs in humans.
“Central injections will for obvious reasons never be a common way to administer drugs in humans.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ IntroductionFrom a statistical point of view this problem might not be any more serious for this field than other domains of psychology or neuroscience in general.
“From a statistical point of view this problem might not be any more serious for this field than other domains of psychology (20, 21, 31) or neuroscience in general (14).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [20] Bakker, 2012, The rules of the game called psychological science, Perspect Psychol Sci source
- cites [21] Pashler, 2012, Is the replicability crisis overblown? Three arguments examined, Perspect Psychol Sci source
- cites [31] Bertamini, 2012, Bite-size science and its undesired side effects, Perspect Psychol Sci source
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitation§ IntroductionThe larger effect size for autism compared to all clinical studies could indicate that focusing on disorders characterized by deficits in social-communicative skills could produce reliable results.
“However, the larger effect size for autism (d=0.57) compared to all clinical studies (d=0.32) could indicate that focusing on disorders characterized by deficits in social-communicative skills could produce reliable results.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
The pre-study odds (R) for behavioral intranasal oxytocin studies in humans is considerably lower than for phase III clinical trials.
“It seems reasonable however to assume that it is considerably lower than for phase III clinical trials.”
The paper relies on this without support.
The studies included in the meta-analyses are representative of the field of intranasal oxytocin studies.
“If the studies included in the meta-analyses are representative of the field, statistical power values of 16% for studies investigating IN-OT effects in healthy subjects and 12% in clinical trials are certainly very low, but not very different from studies in neuroscience in general (average power = 21%) (14).”
The paper relies on this without support.
Studying behavioral effects of oxytocin is at the moment a hot research topic, attracting many new research groups, and studies within this field have been published in very high impact journals such as Science and Nature.
“Studying behavioral effects of OT is at the moment a hot research topic, attracting many new research groups, and studies within this field have been published in very high impact journals such as Science and Nature.”
The paper relies on this without support.
Nasal sprays purportedly containing oxytocin are available on the internet for a variety of indications.
“Nasal sprays purportedly containing OT are available on the internet for a variety of indications”
The paper relies on this without support.
Parents are increasingly seeking intranasal oxytocin as a therapy for their children with autism.
“parents are increasingly seeking IN-OT as a therapy for their children with autism.”
The paper relies on this without support.
The 33 intranasal oxytocin papers published in 2014 are representative of the field of behavioral intranasal oxytocin studies.
“We investigated to what extent low power is reflected in behavioral IN-OT studies by examining the proportion of positive effects published in 2014 (described in Supplemental information).”
The paper relies on this without support.
OT enhances the salience and reinforcing value of social stimuli in animals.
“Research in animals suggest that OT enhances the salience and reinforcing value of social stimuli”
The paper relies on this without support.
The vole partner preference test results with central OT/vasopressin manipulation are informative about human IN-OT effect sizes.
“Specifically, we focused on vole studies using the partner preference test to assess behavior, a literature well known by the authors.”
“these results indicate that larger effect sizes can be achieved by more efficient routes of administration.”
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?
A recent meta-analysis demonstrated that most intranasal oxytocin studies are dramatically underpowered and report overestimated effects.
“A recent meta-analysis of published studies involving IN-OT in humans (21) demonstrated that most studies are dramatically underpowered 1 and report overestimated effects.”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [21]
The Introduction reports that human IN-OT studies are considerably underpowered and that their reported effects have a high probability of being overestimated. The citing sentence presents overestimation as established fact, whereas the source states it as a probability. The paper also reanalyzes data from three existing meta-analyses rather than describing itself as a single meta-analysis. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe absence of a convincing theoretical framework that predicts which moderators exert effects and when has raised skepticism about the robustness of human behavioral intranasal oxytocin research.
“The lack of a convincing theoretical framework that allows to predict which moderators exert their effects and when, has raised healthy skepticism regarding the robustness of human behavioral IN-OT research (20,21).”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [21]
The Introduction says that human intranasal oxytocin research investigates a wide range of outcomes beyond what prior animal research can reasonably predict, and urges skepticism about individual findings. It does not specifically identify the absence of a framework predicting which moderators act and when as the reason for that skepticism. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe meta-analysts estimated that the false discovery rate in the intranasal oxytocin literature is over 80%.
“The meta-analysts estimated (using information on power, pre-study odds and the alpha level) that the false discovery rate in the IN-OT literature is over 80%.”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [21]
The Introduction estimates a positive predictive value of no more than 24% under one set of assumptions, implying a false-discovery proportion of at least 76%, not over 80%. It also gives a 17% positive predictive value—implying 83% false discoveries—but only for a scenario involving ten independent tests and selective reporting. The claim omits that condition and presents the over-80% figure as an estimate for the literature generally. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe authors' studies, like most published intranasal oxytocin studies, might be underpowered.
“our studies, like most published studies on IN-OT, might be underpowered (21).”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [21]
The use of too small samples and the vast amount of candidate moderators might inflate the false discovery rate unless direct replication and correction for multiple hypotheses are applied.
“the use of too small samples (21) and the vast amount of candidate factors that could potentially moderate IN-OT's behavioral effects (19, 20) might inflate the false discovery rate unless direct replication efforts and correction for multiple hypotheses are applied.”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [21]
The efficacy of oxytocin in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability.
“The efficacy of oxytocin (OT) in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability (1–3).”
From Oxytocin under opioid antagonism leads to supralinear enhancement of social attention (2017) · cites this paper as [2]
There is a significant gap in understanding the neural systems responsive to oxytocin and vasopressin in primates, and intranasal oxytocin use in humans has advanced despite lack of knowledge of the mechanism or targets engaged.
“Specifically, there has been a significant gap in the understanding of the neural systems responsive to OT and AVP in primates, and the use of intranasal OT (IN-OT) in humans, in particular, has advanced rapidly despite a lack of knowledge of the mechanism or neurological targets engaged by this manipulation (11-13).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [11]
Human IN-OT studies often lack power because effect sizes are modest, making few-subject studies unreliable.
“IN-OT studies even in humans are often underpowered given the modest effect sizes, making the interpretation of studies with few subjects unreliable (11).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [11]
Recent reviews have criticized the quality and rigor of oxytocin research.
“In response to recent reviews that are critical of the quality and rigor of OXT research (Churchland & Winkielman, 2012;Leng & Ludwig, 2016;Walum, Waldman, & Young, 2016)”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Walum, Waldman, & Young, 2016
Walum and colleagues argued that more than 300 participants are needed for sufficient power, against an average of 49 participants in earlier between-subjects studies.
“Walum et al. (2016) also raised concerns about the power of OXT studies, suggesting that a sample size of more than 300 participants is needed to achieve sufficient power, compared to the average of 49 participants (between-subjects) used in previous studies.”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Walum et al. (2016)
Given the small sample size, it is possible that the observed treatment effect is overestimated.
“given the small sample size, it is possible that the observed treatment effect is overestimated 89.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [89]
Inadequate power has been suggested to be a particularly big problem in oxytocin research and the potential source of the wide range of different and sometimes contradictory findings arising from different studies.
“This has been suggested to be a particularly big problem in oxytocin research and the potential source of the wide range of different and sometimes contradictory findings arising from different studies (Walum et al., 2016).”
From Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions (2017) · cites this paper as Walum et al., 2016
Sample size estimation indicated that 80 6-person groups were needed to detect a significant effect based on an estimated average small-to-medium effect size of oxytocin effect on social behaviors (d = 0.28).
“Based on an estimated average small-to-medium effect size of oxytocin effect on social behaviors (d = 0.28, Walum et al., 2016), 80 6-person groups were needed to detect a significant effect (α = 0.05, β = 0.85, ANOVA: repeated measures, within-between interaction, G-Power, Faul et al., 2009).”
From Oxytocin promotes coordinated out-group attack during intergroup conflict in humans (2019) · cites this paper as Walum et al., 2016
The effect sizes in most IN-OT studies are small.
“the effect sizes in most IN-OT studies are small [46]”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [46]
Most studies examining oxytocin effects have too small sample sizes to even detect medium effects and are therefore substantially underpowered.
“It has been criticized that most studies examining oxytocin effects have too small sample sizes to even detect medium effects and are therefore substantially underpowered98.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [98]
The mounting popularity of studying oxytocin in the social sciences is associated with waves of criticism because papers often suffered from small sample size, low statistical power, inflated effect sizes, inconsistent experimental procedures, and publication bias.
“However, the mounting popularity of studying OT in the social sciences is currently associated with waves of criticism, because papers often have suffered from small sample size, low statistical power, inflated effect sizes, inconsistent experimental procedures , and publication bias 18,19 .”
From A registered replication study on oxytocin and trust (2020) · cites this paper as [18]
The number of participants needed to achieve 80% power for the small-to-medium average effect size of d=0.32 in a within-participants trial is 79 individuals with ASD.
“recruiting and testing 79 individuals with ASD in a within-participants trial—the number of participants needed to achieve 80% power for the small-to-medium average effect size of d=0.32—would be difficult for many research groups”
Many oxytocin studies are statistically underpowered, with clinical studies having an average of 12% statistical power to detect the median Cohen's d of 0.32.
“Many oxytocin studies are statistically underpowered, with clinical studies having an average of 12% statistical power to detect the median Cohen’s d of 0.32.28”
The corresponding average false-negative rate in oxytocin studies is large (88%), which probably contributes to poor replication rates.
“Therefore, the corresponding average false-negative rate is large (88%), which probably contributes to poor replication rates.”
The average effect of intranasal oxytocin on social cognition is d = 0.28.
“On average, tests from these unpublished studies were only sufficiently powered to detect an effect of d = 0.78, which is much larger than the average effect of intranasal oxytocin on social cognition of d = 0.28 (Walum et al., 2016).”
From Revisiting non-significant effects of intranasal oxytocin using equivalence testing (2018) · cites this paper as Walum et al., 2016
Intranasal oxytocin studies have come under increasing scrutiny, particularly regarding statistical power.
“Intranasal oxytocin studies have come under increasing scrutiny, particularly regarding statistical power (Walum et al., 2016).”
From Revisiting non-significant effects of intranasal oxytocin using equivalence testing (2018) · cites this paper as Walum et al., 2016
Intranasal oxytocin studies reported in the literature contain tests that are generally statistically underpowered.
“A related issue is that intranasal oxytocin studies reported in the literature contain tests that are generally statistically underpowered (Walum et al., 2016).”
From Revisiting non-significant effects of intranasal oxytocin using equivalence testing (2018) · cites this paper as Walum et al., 2016
Smaller studies can sometimes overestimate effect sizes even when no true effect is present.
“It is possible that these findings were driven by the fact that smaller studies can sometimes overestimate effect sizes even when no true effect is present (Walum et al., 2016;Zhang et al., 2013).”
From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Walum et al., 2016
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.
Healthy-subject and clinical-trial power values are reversed
MinorThe paper first assigns 16% average power to healthy-subject studies and 12% to clinical trials. Its description of Figure 3 assigns those values in the opposite order.
“Three values, 12%, 16% and 80%, are used for power, representing the average power of studies of IN-OT in healthy subjects, in clinical trials and the standard for adequacy, respectively.”
“If the studies included in the meta-analyses are representative of the field, statistical power values of 16% for studies investigating IN-OT effects in healthy subjects and 12% in clinical trials are certainly very low”
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MethodWhy Most Published Research Findings Are False
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BackgroundPower failure: why small sample size undermines the reliability of neuroscience
Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3475 · Cited by 7,641 · cited 3× · see citing works
“From a statistical point of view this problem might not be any more serious for this field than other domains of psychology (20, 21, 31) or neuroscience in general (14).”
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“As shown by Simmons et al. (2011), Type I errors are easily inflated when researchers allow themselves to employ undisclosed analytic flexibility regarding choice of statistical model, definition of variables, and the rationale for exclusion of outliers (27).”
BackgroundWhy Most Published Research Findings Are False
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“For example, if data from 10 independent tests are collected and only reported for one of these, the statistical power is 16% for all tests and the R-value is 0.10, then the PPV goes down from 24% to 17%.”
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“Large-scale collaboration efforts have been successful within fields like human genetics (33) and psychology (34) and replicated findings from these consortia can be considered more reliable.”
BackgroundMeasuring the Prevalence of Questionable Research Practices With Incentives for Truth Telling
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BackgroundBelieve it or not: how much can we rely on published data on potential drug targets?
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“Bias of this kind could have serious consequences such as failure to replicate findings (24), and there are also reasons to believe that publication bias is more likely to affect low powered studies (25).”
BackgroundSocial effects of oxytocin in humans: context and person matter
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Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias
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“Bias of this kind could have serious consequences such as failure to replicate findings (24), and there are also reasons to believe that publication bias is more likely to affect low powered studies (25).”
BackgroundWhy Most Discovered True Associations Are Inflated
Ioannidis, J. P. A. (2008) · Epidemiology · doi:10.1097/ede.0b013e31818131e7 · Cited by 1,495 · cited 1× · see citing works
“Further, in situations when an underpowered study detects a true effect, the estimate of this effect size is likely to be highly exaggerated, a phenomenon often referred to as the “winner’s curse” (15).”
BackgroundThe appropriateness of asymmetry tests for publication bias in meta-analyses: A large survey
Ioannidis, J. P. A., & Trikalinos, T. A. (2007) · Canadian Medical Association Journal · doi:10.1503/cmaj.060410 · Cited by 1,052 · see citing works
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
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Erroneous analyses of interactions in neuroscience: A problem of significance
Nieuwenhuis, S., Forstmann, B. U., & Wagenmakers, E.-J. (2011) · Nature Neuroscience · doi:10.1038/nn.2886 · Cited by 864 · cited 1× · see citing works
“Use of multiple analyses on the same data set and selective reports of statistical methods used, or insufficient correction for multiple comparisons, can cause inflation in effects (29).”
MethodOxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior
Ross, H. E., & Young, L. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.004 · Cited by 856 · see citing works
Self-citationThe rules of the game called psychological science
Bakker, M., van Dijk, A., & Wicherts, J. M. (2012) · Perspectives on Psychological Science · doi:10.1177/1745691612459060 · Cited by 800 · cited 2× · see citing works
“From a statistical point of view this problem might not be any more serious for this field than other domains of psychology (20, 21, 31) or neuroscience in general (14).”
BackgroundOxytocin increases gaze to the eye region of human faces
Guastella, A. J., Mitchell, P. B., & Dadds, M. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.06.026 · Cited by 798 · see citing works
“Positive” results increase down the Hierarchy of the Sciences
Fanelli, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010068 · Cited by 734 · cited 1× · see citing works
“When reading the literature on behavioral IN-OT studies in humans it is obvious that most papers report positive findings, which is in line with a study by Fanelli showing that more than 80% of scientific publications in various sciences report positive results (22).”
ResultIs the Replicability Crisis Overblown? Three Arguments Examined
Pashler, H., & Harris, C. R. (2012) · Perspectives on Psychological Science · doi:10.1177/1745691612463401 · Cited by 697 · cited 4× · see citing works
“If about 10% of all postulated hypotheses are correct, similar to what is expected for experimental psychology in general (21), we would expect, in the absence of bias, that only about 2% of the investigated effects would turn out to be statistically significant.”
BackgroundInfluentialIntranasal Oxytocin: Myths and Delusions
Leng, G., & Ludwig, M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.003 · Cited by 615 · cited 1× · see citing works
“Although the idea that manipulating OT in humans could influence social behavior is supported by rigorous animal research, we argue that the pre-study odds of studies investigating the effect of IN-OT still would be low, primarily due to limitations in deep brain penetration of OT when administered intranasally (2, 19…”
BackgroundAn Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science
Open Science Collaboration (2012) · Perspectives on Psychological Science · doi:10.1177/1745691612462588 · Cited by 605 · see citing works
Modulating social behavior with oxytocin: How does it work? What does it mean?
Churchland, P. S., & Winkielman, P. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.003 · Cited by 464 · cited 1× · see citing works
“Although the idea that manipulating OT in humans could influence social behavior is supported by rigorous animal research, we argue that the pre-study odds of studies investigating the effect of IN-OT still would be low, primarily due to limitations in deep brain penetration of OT when administered intranasally (2, 19…”
BackgroundBakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.34 · Cited by 383 · cited 4× · see citing works
“Finally, in the meta-analysis by BakermansKranenburg and Van IJzendoorn (11) IN-OT seems to have the largest effect size in individuals with autism.”
BackgroundMethodInfluentialLoup, F., Tribollet, E., Dubois-Dauphin, M., & Dreifuss, J. J. (1991) · Brain Research · doi:10.1016/0006-8993(91)90345-v · Cited by 378 · cited 1× · see citing works
“For example, OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43), consistent with the putative localization of OT receptors in human brain (44).”
BackgroundExogenous and evoked oxytocin restores social behavior in the <i>Cntnap2</i> mouse model of autism
Peñagarikano, O., Lázaro, M. T., Lu, X.-H., Gordon, A., Dong, H., Lam, H. A., Peles, E., Maidment, N. T., Murphy, N. P., Yang, X. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010257 · Cited by 378 · cited 1× · see citing works
“For example, melanocortin receptor agonists potentiate central OT release in the brain (37, 38), facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40), and mimic the prosocial effects of OT in a mouse model of autism (41).”
BackgroundVan IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.008 · Cited by 365 · cited 1× · see citing works
“Van IJzendoorn and Bakersmans-Kranenburg investigated the effect of IN-OT on facial emotion recognition (13 effect sizes, total N = 408), trust to in-group (8 effect sizes, total N = 317) and trust to out-group (10 effect sizes, total N = 505) (9).”
BackgroundGuastella, A. J., Hickie, I. B., McGuinness, M. M., Otis, M., Woods, E. A., Disinger, H. M., Chan, H.-K., Chen, T. F., & Banati, R. B. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.11.019 · Cited by 357 · see citing works
Shahrestani, S., Kemp, A. H., & Guastella, A. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.86 · Cited by 283 · cited 1× · see citing works
“conducted a meta-analysis of studies examining the effect of OT on recognition of basic emotions (7 effect sizes, total N = 381)(10).”
MethodNeuropeptides and the evolution of social behavior
Insel, T. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00146-x · Cited by 264 · cited 1× · see citing works
“Even though it is possible that the IN-OT literature so far contains a relatively high proportion of false positive findings we believe the behavioral effects of OT are indeed evolutionary conserved (6, 32) and that the evidence from rodent research is compelling.”
BackgroundAuyeung, B., Lombardo, M. V., Heinrichs, M., Chakrabarti, B., Sule, A., Deakin, J. B., Bethlehem, R. A. I., Dickens, L., Mooney, N., Sipple, J. A. N., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.146 · Cited by 234 · see citing works
The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies
Modi, M. E., & Young, L. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.010 · Cited by 218 · cited 3× · see citing works
“For example, melanocortin receptor agonists potentiate central OT release in the brain (37, 38), facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40), and mimic the prosocial effects of OT in a mouse model of autism (41).”
BackgroundSelf-citationSkuse, D. H., Lori, A., Cubells, J. F., Lee, I., Conneely, K. N., Puura, K., Lehtimäki, T., Binder, E. B., & Young, L. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302985111 · Cited by 207 · see citing works
Self-citationYoung, L. J., & Barrett, C. E. (2015) · Science · doi:10.1126/science.aaa8120 · Cited by 200 · see citing works
Self-citationSabatier, N., Caquineau, C., Dayanithi, G., Bull, P., Douglas, A. J., Guan, X. M. M., Jiang, M., Van der Ploeg, L., & Leng, G. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-32-10351.2003 · Cited by 190 · cited 1× · see citing works
“For example, melanocortin receptor agonists potentiate central OT release in the brain (37, 38), facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40), and mimic the prosocial effects of OT in a mouse model of autism (41).”
BackgroundFreeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.023 · Cited by 185 · cited 1× · see citing works
“For example, OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43), consistent with the putative localization of OT receptors in human brain (44).”
BackgroundPereira, T. V., & Ioannidis, J. P. A. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.12.012 · Cited by 160 · cited 1× · see citing works
“Even though summary effects from meta-analyses can be inflated due to various sources of bias (8), these analyses provide the best estimates of the true effect size.”
BackgroundFreeman, S. M., Walum, H., Inoue, K., Smith, A. L., Goodman, M. M., Bales, K. L., & Young, L. J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.055 · Cited by 153 · cited 1× · see citing works
“For example, OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43), consistent with the putative localization of OT receptors in human brain (44).”
BackgroundSelf-citationBarrett, C. E., Arambula, S. E., & Young, L. J. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.73 · Cited by 115 · cited 1× · see citing works
“For example, melanocortin receptor agonists potentiate central OT release in the brain (37, 38), facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40), and mimic the prosocial effects of OT in a mouse model of autism (41).”
BackgroundSelf-citationIntranasal oxytocin effects on social cognition: A critique
Evans, S. L., Dal Monte, O., Noble, P., & Averbeck, B. B. (2014) · Brain Research · doi:10.1016/j.brainres.2013.11.008 · Cited by 97 · see citing works
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Self-citationEditorial comment: Oxytocin, vasopressin and social behavior
Young, L. J., & Flanagan-Cato, L. M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.019 · Cited by 81 · cited 1× · see citing works
“Much of the excitement regarding OT over the past decade has been driven by a remarkable proliferation of research suggesting that intranasal OT (IN-OT) administration influences various aspects of human social behavior (7).”
BackgroundSelf-citationTrial unpredictability yields predictable therapy gains
Djulbegovic, B., Kumar, A., Glasziou, P., Miladinovic, B., & Chalmers, I. (2013) · Nature · doi:10.1038/500395a · Cited by 66 · cited 1× · see citing works
“Data suggest that the R for phase III clinical trials is approximately 1, meaning that in about 50% of the time the drugs that make it to these trials are more effective than the current “gold standard” treatment (18).”
BackgroundOxytocin, social cognition and psychiatry
Young, L. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.186 · Cited by 64 · see citing works
Self-citationBite-size science and its undesired side effects
Bertamini, M., & Munafò, M. R. (2012) · Perspectives on Psychological Science · doi:10.1177/1745691611429353 · Cited by 62 · cited 1× · see citing works
“From a statistical point of view this problem might not be any more serious for this field than other domains of psychology (20, 21, 31) or neuroscience in general (14).”
BackgroundBias in genetic association studies and impact factor
Munafò, M. R., Stothart, G., & Flint, J. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.77 · Cited by 60 · cited 1× · see citing works
“In addition, it has been shown that the more popular or “trendy” a scientific field is the less likely it is to generate true findings (16) and the extent to which a study overestimates true effects is positively correlated with the impact factor of a journal (30).”
BackgroundBarrett, C. E., Modi, M. E., Zhang, B. C., Walum, H., Inoue, K., & Young, L. J. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.05.041 · Cited by 34 · see citing works
Self-citationEmpirical evidence for low reproducibility indicates low pre-study odds
Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3475-c6 · Cited by 21 · cited 1× · see citing works
“have argued that large-scale phase III clinical trials represent the case when the value of R will be the highest (17).”
Background
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Trends in peptide drug discovery
Muttenthaler, M., King, G. F., Adams, D. J., & Alewood, P. F. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00135-8 · Cited by 2,022 · see citing works
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 · see citing works
Music as a coevolved system for social bonding
Savage, P. E., Loui, P., Tarr, B., Schachner, A., Glowacki, L., Mithen, S., & Fitch, W. T. (2020) · Behavioral and Brain Sciences · doi:10.1017/s0140525x20000333 · Cited by 594 · see citing works
Quintana, D. S., & Williams, D. R. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1761-4 · Cited by 415 · see citing works
“This is consistent with recent concerns surrounding statistically underpowered oxytocin studies [36].”
BackgroundResultThe neural mechanisms and circuitry of the pair bond
Walum, H., & Young, L. J. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0072-6 · Cited by 353 · see citing works
Self-citationQuintana, D. S., Lischke, A., Grace, S., Scheele, D., Ma, Y., & Becker, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00864-7 · Cited by 263 · see citing works
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 · see citing works
“surfaced in the field of psychological and psychiatric oxytocin research (9,36,37).”
Prefrontal–amygdala circuits in social decision-making
Gangopadhyay, P., Chawla, M., Monte, O. D., & Chang, S. W. C. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00738-9 · Cited by 247 · see citing works
Meaningful associations in the adolescent brain cognitive development study
Dick, A. S., Lopez, D. A., Watts, A. L., Heeringa, S. G., Reuter, C., Bartsch, H., Fan, C. C., Kennedy, D. N., Palmer, C. E., Marshall, A. T., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118262 · Cited by 234 · see citing works
“…2017 ). ther studies in the field suffer from false positives that do not replicate, nd overestimation of effect sizes in general, which typically arise from research environment consisting of many small studies, p-hacking, and ublication bias towards positive findings ( Walum et al., 2016 ).”
Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice
Ferretti, V., Maltese, F., Contarini, G., Nigro, M., Bonavia, A., Huang, H., Gigliucci, V., Morelli, G., Scheggia, D., Managò, F., et al. (2019) · Current Biology · doi:10.1016/j.cub.2019.04.070 · Cited by 212 · see citing works
An Allostatic Theory of Oxytocin
Quintana, D. S., & Guastella, A. J. (2020) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2020.03.008 · Cited by 212 · see citing works
“Although efforts have beenmade to address these limitations – in terms of better understanding of intranasal oxytocin administration [16–18], identifying the dose–response of intranasal oxytocin [19–21], and improving study design [22,23] – the lack of an overarching theory that accounts for the function of oxytocin a…”
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“IN-OT studies even in humans are often underpowered given the modest effect sizes, making the interpretation of studies with few subjects unreliable (11).”
BackgroundSelf-citationKing, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.008 · Cited by 191 · see citing works
“Individual reports of the effects of intranasal OXT should be interpreted cautiously (11).”
Self-citationBrain oxytocin: how puzzle stones from animal studies translate into psychiatry
Grinevich, V., & Neumann, I. D. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0802-9 · Cited by 189 · see citing works
“Moreover, a controversial discussion is still addressing questions regarding the reliability and validity of human OXT studies [158] due to small sample sizes and low statistical power, and lack of detailed dose-response studies.”
BackgroundYamasue, H., Okada, T., Munesue, T., Kuroda, M., Fujioka, T., Uno, Y., Matsumoto, K., Kuwabara, H., Mori, D., Okamoto, Y., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0097-2 · Cited by 185 · see citing works
Johnson, Z. V., Walum, H., Jamal, Y. A., Xiao, Y., Keebaugh, A. C., Inoue, K., & Young, L. J. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.11.011 · Cited by 190 · see citing works
“…OT administration increases functional connectivity across a variety of striatal and limbic nuclei during various social contexts (Fan et al., 2015; Gorka et al., 2015; Hu et al., 2015; Riem et al., 2012); however, studies using intranasal OT should be interpreted with caution (Walum et al., 2015).”
Self-citationMeta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions
Leppanen, J., Ng, K. W., Tchanturia, K., & Treasure, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.010 · Cited by 188 · see citing works
“This has been suggested to be a particularly big problem in oxytocin research and the potential source of the wide range of different and sometimes contradictory findings arising from different studies (Walum et al., 2016).”
The New Statistics for Better Science: Ask How Much, How Uncertain, and What Else Is Known
Calin-Jageman, R. J., & Cumming, G. (2019) · The American Statistician · doi:10.1080/00031305.2018.1518266 · Cited by 170 · see citing works
“A recent meta-analysis of studies manipulating oxytocin in humans found a median sample-size of just 25 participants/group (Walum et al. 2016).”
BackgroundInfluentialEstimation for Better Inference in Neuroscience
Calin-Jageman, R. J., & Cumming, G. (2019) · eNeuro · doi:10.1523/eneuro.0205-19.2019 · Cited by 145 · see citing works
“These concerns are so severe that a recent review concluded that the entire literature up to that point should be viewed with “healthy skepticism” because most published effects are probably spurious (Walum et al., 2016, p. 251).”
BackgroundInfluentialOxytocin and Pain Perception: From Animal Models to Human Research
Boll, S., de Minas, A. C. A., Raftogianni, A., Herpertz, S. C., & Grinevich, V. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.09.041 · Cited by 137 · see citing works
Oxytocin and the Neurobiology of Prosocial Behavior
Marsh, N., Marsh, A. A., Lee, M. R., & Hurlemann, R. (2020) · The Neuroscientist · doi:10.1177/1073858420960111 · Cited by 149 · see citing works
Waller, R. E., & Wagner, N. J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.005 · Cited by 138 · see citing works
A registered replication study on oxytocin and trust
Declerck, C. H., Boone, C., Pauwels, L., Vogt, B., & Fehr, E. (2020) · Nature Human Behaviour · doi:10.1038/s41562-020-0878-x · Cited by 137 · see citing works
Lane, A., Luminet, O., Nave, G., & Mikolajczak, M. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12384 · Cited by 134 · see citing works
Overview of human oxytocin research
Kendrick, K. M., Guastella, A. J., & Becker, B. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_19 · Cited by 121 · see citing works
Neural Mechanisms of Social Cognition in Primates
Wittmann, M. K., Lockwood, P. L., & Rushworth, M. F. S. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-061450 · Cited by 113 · see citing works
“For example, oxytocin affects social behavior in rodents, monkeys, and humans (Tremblay et al. 2017), although there is debate over the size and nature of effects (Leng & Ludwig 2016, Walum et al. 2016).”
BackgroundGrace, S. A., Rossell, S. L., Heinrichs, M., Kordsachia, C., & Labuschagne, I. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.031 · Cited by 120 · see citing works
Adolescent Brain Cognitive Development (ABCD) Community MRI Collection and UtilitiesPreprint
Feczko, E., Conan, G., Marek, S. A., Tervo‐Clemmens, B., Cordova, M., Doyle, O. J., Earl, E., Perrone, A. J., Sturgeon, D., Klein, R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.09.451638 · Cited by 119 · see citing works
“Because most studies operate as small sample siloes, publication bias overestimates effects and limits replicability (Marek et al., 2020; Sabuncu et al., 2015; Smith and Nichols, 2018; Walum et al., 2016).”
BackgroundOxytocin receptors modulate a social salience neural network in male prairie voles
Johnson, Z. V., Walum, H., Xiao, Y., Riefkohl, P. C., & Young, L. J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.10.009 · Cited by 113 · see citing works
“investigations using intranasal OT should be interpreted with caution (Leng and Ludwig, 2016; Walum et al., 2016).”
Self-citationSmith, A. S., Korgan, A. C., & Young, W. S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104324 · Cited by 107 · see citing works
Pair-bonding, fatherhood, and the role of testosterone: a meta-analytic review
Grebe, N. M., Sarafin, R. E., Strenth, C. R., & Zilioli, S. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.01.010 · Cited by 116 · see citing works
Music as a coevolved system for social bondingPreprint
Savage, P. E., Loui, P., Tarr, B., et al. (2020) · doi:10.31234/osf.io/qp3st · Cited by 113 · see citing works
Social Decision-Making and the Brain: A Comparative Perspective
Tremblay, S., Sharika, K. M., & Platt, M. L. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.01.007 · Cited by 105 · see citing works
Quintana, D. S., Westlye, L. T., Hope, S., Nærland, T., Elvsåshagen, T., Dørum, E., Rustan, Ø., Valstad, M., Rezvaya, L., Lishaugen, H., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.103 · Cited by 111 · see citing works
Steinman, M. Q., Duque-Wilckens, N., & Trainor, B. C. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.10.008 · Cited by 105 · see citing works
Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women
Bethlehem, R. A. I., Lombardo, M. V., Lai, M.-C., Auyeung, B., Crockford, S. K., Deakin, J., Soubramanian, S., Sule, A., Kundu, P., Voon, V, et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.72 · Cited by 96 · see citing works
Evidence for Intranasal Oxytocin Delivery to the brain: Recent Advances and Future Perspectives
Quintana, D. S., Smerud, K. T., Andreassen, O. A., & Djupesland, P. G. (2018) · Therapeutic Delivery · doi:10.4155/tde-2018-0002 · Cited by 94 · see citing works
Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities
Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M. (2017) · Chronic Stress · doi:10.1177/2470547016687996 · Cited by 99 · see citing works
“Improved research standards including increased statistical power and reporting on trials without expected results are needed before IN OT can be utilized as a first-line treatment for stress-related disorders.(201)”
BackgroundDaughters, K., Manstead, A. S. R., Hubble, K., Rees, A., Thapar, A., & van Goozen, S. H. M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0145104 · Cited by 92 · see citing works
Oxytocin effects in schizophrenia: Reconciling mixed findings and moving forward
Bradley, E., & Woolley, J. D. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.007 · Cited by 88 · see citing works
“…oxytocin literature is limited by small sample sizes, failures to replicate (Nave et al., 2015), disputed statistical approaches (Conlisk, 2011; Walum et al., 2015), incomplete understanding of pharmacodynamics (Leng and Ludwig, 2016), possible publication bias (Lane et al., 2016), and…”
Alvares, G. A., Quintana, D. S., & Whitehouse, A. J. O. (2017) · Autism Research · doi:10.1002/aur.1692 · Cited by 91 · see citing works
Oxytocin promotes coordinated out-group attack during intergroup conflict in humans
Zhang, H., Gross, J., De Dreu, C., & Ma, Y. (2019) · eLife · doi:10.7554/elife.40698 · Cited by 87 · see citing works
Effect sizes of associations between neuroimaging measures and affective symptoms: A meta‐analysis
Feng, C., Thompson, W. K., & Paulus, M. P. (2021) · Depression and Anxiety · doi:10.1002/da.23215 · Cited by 87 · see citing works
“Indeed, underpowered studies do not only result in a failure to detect smaller effects, but also lead to exaggeration of effect sizes, a phenomenon due to selective reporting bias known as “the winner's curse” (Button et al., 2013; Walum et al., 2016).”
BackgroundLower Oxytocin Plasma Levels in Borderline Patients with Unresolved Attachment Representations
Jobst, A., Padberg, F., Mauer, M.-C., Daltrozzo, T., Bauriedl-Schmidt, C., Sabass, L., Sarubin, N., Falkai, P., Renneberg, B., Zill, P., et al. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00125 · Cited by 88 · see citing works
“Recently published articles argue that peripheral OT cannot give information about cognition, emotion and behavior (Meyer-Lindenberg et al., 2011; Quintana and Woolley, 2015; Leng and Ludwig, 2016; Walum et al., 2016).”
BackgroundOxytocin modulates social value representations in the amygdala
Liu, Y., Li, S., Lin, W., Li, W., Yan, X., Wang, X., Pan, X., Rutledge, R. B., & Ma, Y. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0351-1 · Cited by 89 · see citing works
Pohl, T. T., Young, L. J., & Bosch, O. J. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2017.12.011 · Cited by 83 · see citing works
Self-citationA Guide for Calculating Study-Level Statistical Power for Meta-Analyses
Quintana, D. S. (2023) · Advances in Methods and Practices in Psychological Science · doi:10.1177/25152459221147260 · Cited by 95 · see citing works
“, 2017), which has partly been attributed to study designs with low statistical power (Quintana, 2020; Walum et al., 2016).”
BackgroundA review of human male field studies of hormones and behavioral reproductive effort
Gray, P. B., McHale, T. S., & Carré, J. M. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.07.004 · Cited by 81 · see citing works
“Unfortunately, this effect has not been replicated (Nave et al., 2015) and several authors have argued that the oxytocin administration literature is plagued by low powered studies (Walum et al., 2016), publication bias and false positives (Lane et al., 2016; Leng and Ludwig, 2016).”
Bürkner, P., Williams, D. R., Simmons, T. C., & Woolley, J. D. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx053 · Cited by 80 · see citing works
Oxytocin Modulation of Neural Circuits
Mitre, M., Minder, J. L., Morina, E., Chao, M. V., & Froemke, R. C. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_7 · Cited by 76 · see citing works
Loth, M. K., & Donaldson, Z. R. (2020) · Endocrinology · doi:10.1210/endocr/bqaa223 · Cited by 74 · see citing works
“A growing human research literature has begun investigating the endocrine basis of human pair bonding via multiple perspectives— for instance, by measuring peripheral hormone levels and manipulating nonapeptide systems through intranasal delivery of oxytocin (OXT) and via genetic studies linking variation in pair bond…”
BackgroundAntisocial oxytocin: Complex effects on social behavior
Beery, A. K. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.11.006 · Cited by 74 · see citing works
A, T. R. D. J., & Neumann, I. D. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_13 · Cited by 74 · see citing works
Buttner, A. P. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.08.029 · Cited by 67 · see citing works
“(2005). Evaluating the temperament in shelter dogs.”
Peled‐Avron, L., Abu-Akel, A. M., & Shamay‐Tsoory, S. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.023 · Cited by 73 · see citing works
Sannino, S., Chini, B., & Grinevich, V. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22450 · Cited by 70 · see citing works
“OT administration is currently proposed as a treatment for high prevalence conditions such as autism and schizophrenia, (Feifel et al., 2016; Guastella and Hichie, 2016), even in the presence of some inconsistent results (Walum et al., 2016).”
ResultNeuropeptide diversity and the regulation of social behavior in New World primates
French, J. A., Taylor, J. H., Mustoe, A. C., & Cavanaugh, J. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.03.004 · Cited by 66 · see citing works
Face individual identity recognition: a potential endophenotype in autism
Minio-Paluello, I., Porciello, G., Pascual‐Leone, Á., & Baron‐Cohen, S. (2020) · Molecular Autism · doi:10.1186/s13229-020-00371-0 · Cited by 67 · see citing works
“This face IIR-based stratification of participants may help addressing the failure of many [152, 153], often underpowered [154], INOXY intervention studies with autistic participants.”
BackgroundJiang, Y., & Platt, M. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-25607-1 · Cited by 66 · see citing works
Oxytocin reduces amygdala responses during threat approach
Radke, S., Volman, I., Kokal, I., Roelofs, K., de Bruijn, E. R. A., & Toni, I. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.02.028 · Cited by 67 · see citing works
“Furthermore, given the rising concerns on imited statistical power and effect-size inflation of oxytocin studes (e.g., Walum et al., 2016), replication of the present results s crucial, preferably in a within-subject instead of the current etween-subject design.”
BackgroundTargeting the Oxytocin System: New Pharmacotherapeutic Approaches
Gulliver, D. W., Werry, E. L., Reekie, T. A., Katte, T. A., Jorgensen, W. T., & Kassiou, M. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.11.001 · Cited by 63 · see citing works
“…many of the trials investigating intranasal OT over the past decade have been considerably underpowered, with small patient cohorts and effect sizes, large variations in dosing regimens (10 – 7000 IU) and heterogenous behavioral readouts further complicating the interpretation of study data [26].”
Improving the precision of intranasal oxytocin research
Winterton, A., Westlye, L. T., Steen, N. E., Andreassen, O. A., & Quintana, D. S. (2020) · Nature Human Behaviour · doi:10.1038/s41562-020-00996-4 · Cited by 62 · see citing works
Oxytocin selectively modulates brain response to stimuli probing social synchrony
Lévy, J., Goldstein, A., Zagoory‐Sharon, O., Weisman, O., Schneiderman, I., Eidelman-Rothman, M., & Feldman, R. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.09.066 · Cited by 61 · see citing works
Paloyelis, Y., Krahé, C., Maltezos, S., Williams, S. C., Howard, M. A., & Fotopoulou, A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12347 · Cited by 61 · see citing works
Awake canine fMRI predicts dogs’ preference for praise vs food
Cook, P. F., Prichard, A., Spivak, M., & Berns, G. S. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw102 · Cited by 55 · see citing works
“Although oxytocin supports accounts of social attachment (although see Walum et al. , 2016), the proximal neural mechanisms of social reward in the dog are unknown.”
BackgroundFailed Replication of Oxytocin Effects on Trust: The Envelope Task Case
Lane, A., Mikolajczak, M., Treinen, E., Samson, D., Corneille, O., de Timary, P., & Luminet, O. (2015) · PLOS ONE · doi:10.1371/journal.pone.0137000 · Cited by 61 · see citing works
“Furthermore, a recent meta-analytic investigation on published studies involving intranasal administration of OT in humans [28] demonstrated that those studies are generally underpowered and report overestimated effects.”
BackgroundAssociations between oxytocin and empathy in humans: A systematic literature review
Barchi-Ferreira, A. M., & Osório, F. D. L. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105268 · Cited by 62 · see citing works
Current findings on the role of oxytocin in the regulation of food intake
Spetter, M. S., & Hallschmid, M. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.03.007 · Cited by 58 · see citing works
Effects of intranasal oxytocin on symptoms of schizophrenia: A multivariate Bayesian meta-analysis
Williams, D. R., & Bürkner, P. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.10.013 · Cited by 58 · see citing works
Oxytocin in animal models of autism spectrum disorder
Peñagarikano, O. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22449 · Cited by 54 · see citing works
“…caution before attributing oxytocin a magic role in all kinds of complex socialrelated paradigms, as most of these studies are underpowered (Walum et al., 2016), Notwithstanding, Developmental Neurobiology given that the activation of the oxytocin system is modulated by social stimuli,…”
BackgroundOxytocin under opioid antagonism leads to supralinear enhancement of social attention
Dal Monte, O., Piva, M., Anderson, K. M., Tringides, M., Holmes, A. J., & Chang, S. W. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702725114 · Cited by 55 · see citing works
Ebert, A., & Brüne, M. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_21 · Cited by 62 · see citing works
Oxytocin Selectively Improves Empathic Accuracy: A Replication in Men and Novel Insights in Women
Bartz, J. A., Nitschke, J. P., Krol, S. A., & Tellier, P. (2019) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.01.014 · Cited by 55 · see citing works
Meaningful Effects in the Adolescent Brain Cognitive Development StudyPreprint
Dick, A., Watts, A. L., Heeringa, S., Lopez, D. A., Bartsch, H., Fan, C.-C., Palmer, C., Reuter, C., Marshall, A., Haist, F., et al. (2020) · bioRxiv · doi:10.1101/2020.09.01.276451 · Cited by 27 · see citing works
Sniff and mimic–Intranasal oxytocin increases facial mimicry in a sample of men
Korb, S., Malsert, J., Strathearn, L., Vuilleumier, P., & Niedenthal, P. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.06.003 · Cited by 54 · see citing works
“Finally, although our sample was 22% larger than the median sample size of previous studies, a recent review suggests that much larger groups of participants may be needed to obtain adequate statistical power (Walum et al., 2016).”
ResultPutnam, P. T., Roman, J. M., Zimmerman, P. E., & Gothard, K. M. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.05.016 · Cited by 53 · see citing works
Mierop, A., Mikolajczak, M., Stahl, C., Béna, J., Luminet, O., Lane, A., & Corneille, O. (2020) · Perspectives on Psychological Science · doi:10.1177/1745691620921525 · Cited by 53 · see citing works
“These are familiar recommendations (see, e.g., Walum et al., 2016).”
BackgroundKovács, K., Kis, A., Pogány, Á., Koller, D., & Topál, J. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.09.010 · Cited by 52 · see citing works
“…argued that the field of intranasal oxytocin research would in general benefit from increasing sample sizes and/or conducting replication studies (Walum et al., 2016), and our pioneering results (although using the conventional, relatively low, sample size) suggests that taking into account the…”
Understanding Vulnerability and Adaptation in Early Brain Development using Network Neuroscience
Graham, A. M., Marr, M. C., Buß, C., Sullivan, E. L., & Fair, D. A. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.01.008 · Cited by 49 · see citing works
“, p-hacking) [84], and publication bias towards studies with positive effects [81,85,86].”
BackgroundOxytocin—a social peptide? Deconstructing the evidence
Leng, G., Leng, R., & Ludwig, M. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0055 · Cited by 48 · see citing works
The interplay of oxytocin and sex hormones
Quintana, D. S., Glaser, B. D., Kang, H., Kildal, E. S.-M., Audunsdottir, K., Sartorius, A. M., & Barth, C. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105765 · Cited by 54 · see citing works
“This meta-analysis found that the mean statistical power across all studies was 12.2 % (Quintana, 2020), which was a similar result to an earlier analysis (Walum et al., 2016).”
InfluentialSeeley, S. H., Chou, Y., & O'Connor, M. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.011 · Cited by 42 · see citing works
“IN-OT Standardized protocols would allow for better across-study comparison, and there are several publications detailing statistical and methodological recommendations for IN-OT research (Guastella et al., 2013; Walum et al., 2016).”
On the role of oxytocin in borderline personality disorder
Brüne, M. (2015) · British Journal of Clinical Psychology · doi:10.1111/bjc.12100 · Cited by 50 · see citing works
Neuropeptide Regulation of Social Attachment: The Prairie Vole Model
Tabbaa, M., Paedae, B., Liu, Y., & Wang, Z. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150055 · Cited by 53 · see citing works
Tabak, B. A., Teed, A. R., Castle, E., Dutcher, J. M., Meyer, M. L., Bryan, R., Irwin, M. R., Lieberman, M. D., & Eisenberger, N. I. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.04.019 · Cited by 43 · see citing works
Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
Ford, C. L., & Young, L. J. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.11.007 · Cited by 46 · see citing works
“However, bypassing the blood–brain barrier remains a perennial problem for pharmacological interventions including IN-OT; the effect sizes in most IN-OT studies are small [46] and there are questions surrounding its ability to cross the blood–brain barrier and diffuse to subcortical”
BackgroundSelf-citationRole of oxytocin in parental behaviour
Olazábal, D. E. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12594 · Cited by 47 · see citing works
Oxytocin Reduces Face Processing Time but Leaves Recognition Accuracy and Eye-Gaze Unaffected
Hubble, K., Daughters, K., Manstead, A. S. R., Rees, A., Thapar, A., & van Goozen, S. H. M. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617716000886 · Cited by 42 · see citing works
“In response to recent reviews that have been critical of the quality and rigor of OXT research (Churchland & Winkielman, 2002; Leng & Ludwig, 2016; Walum, Waldman & Young, 2016), we aimed to replicate previous findings of the effects of OXT on facial emotion recognition using a larger sample.”
Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates
Galbusera, A., Felice, A. D., Girardi, S., Bassetto, G., Maschietto, M., Nishimori, K., Chini, B., Papaleo, F., Vassanelli, S., & Gozzi, A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.283 · Cited by 38 · see citing works
Leppanen, J., Ng, K. W., Kim, Y.-R., Tchanturia, K., & Treasure, J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.041 · Cited by 45 · see citing works
“It is possible that these findings were driven by the fact that smaller studies can sometimes overestimate effect sizes even when no true effect is present (Walum et al., 2016; Zhang et al., 2013).”
BackgroundLischke, A., Herpertz, S. C., Berger, C., Domes, G., & Gamer, M. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx107 · Cited by 46 · see citing works
“…oxytocin indeed normalizes BPD patients’ hypersensitivity for emotionally relevant stimuli (Herpertz and Bertsch, 2015), they should be treated with caution until replicated and extended in further studies to prevent an overoptimistic view of oxytocin’s therapeutic potential (Walum et al., 2016).”
BackgroundDeterminants and modulators of human social decisions
Terenzi, D., Liu, L., Bellucci, G., & Park, S. Q. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.041 · Cited by 40 · see citing works
“To sum up, meta-analyses have further indicated the small and unreliable effect size of intranasal oxytocin on trust (Lane et al., 2016; Walum et al., 2016), which suggests a concern about the replicability of oxytocin administration studies on other social behaviors, as well as the effects of…”
BackgroundQuintana, D. S., Dieset, I., Elvsåshagen, T., Westlye, L. T., & Andreassen, O. A. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.12.004 · Cited by 39 · see citing works
“…the mechanisms underlying the role of OT in the development and maintenance of individual MetS risk factors before undertaking a raft of underpowered OT trials (Walum et al., 2016) can accelerate the period of enlightenment for OT and MetS, and if efficacious, a period of research productivity.”
BackgroundResultOxytocin improves facial emotion recognition in young adults with antisocial personality disorder
Timmermann, M., Jeung, H., Schmitt, R., Boll, S., Freitag, C. M., Bertsch, K., & Herpertz, S. C. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.07.483 · Cited by 41 · see citing works
Oxytocin and Anxiety Disorders: Translational and Therapeutic Aspects
Naja, W., & Aoun, M. P. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0819-1 · Cited by 40 · see citing works
Mustoe, A. C., Harnisch, A. M., Hochfelder, B., Cavanaugh, J., & French, J. A. (2016) · Animal Behaviour · doi:10.1016/j.anbehav.2016.01.025 · Cited by 40 · see citing works
Oxytocin regulates reunion affiliation with a pairmate following social separation in marmosets
Cavanaugh, J., Mustoe, A. C., & French, J. A. (2018) · American Journal of Primatology · doi:10.1002/ajp.22750 · Cited by 41 · see citing works
Kwon, H., & Sasaki, J. Y. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108562140 · Cited by 41 · see citing works
Hubble, K., Daughters, K., Manstead, A. S. R., Rees, A., Thapar, A., & van Goozen, S. H. M. (2017) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2017.10.019 · Cited by 41 · see citing works
“In response to recent reviews that are critical of the quality and rigor of OXT research (Churchland & Winkielman, 2012; Leng & Ludwig, 2016; Walum, Waldman, & Young, 2016) and in view of evidence of large variations in individual responsivity to OXT across participants (Daughters et al., 2015), we decided to study th…”
A Novel Role of CD38 and Oxytocin as Tandem Molecular Moderators of Human Social Behavior
Tolomeo, S., Chiao, B., Lei, Z., Chew, S. H., & Ebstein, R. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.013 · Cited by 39 · see citing works
“conundrum of low statistical power in many of the human studies (Walum et al., 2016) and Bartz and co-authors have emphasized the importance of ‘context’ when carrying”
Background
- Authors
- Walum, H., Waldman, I. D., & Young, L. J.
- Affiliations
- Emory University (US)
- Corresponding author
- Walum, Hasse
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 79
- Issue
- 3
- Pages
- 251-257
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4690817
- OpenAlex
- W983974319
- Cited by
- 345
- References
- 51
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 13 · 2023: 16 · 2022: 20 · 2021: 33 · 2020: 33 · 2019: 37 · 2018: 42 · 2017: 53 · 2016: 39 · 2015: 16
- FWCI
- 79.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- NIH (R01MH096983, 1P50MH100023)
- NIH OD (P51OD11132)
- Swedish Brain Foundation
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Psychology Research and Bibliometrics
- Keywords
- intranasal oxytocin, social behavior, social cognition, statistical power, publication bias, reproducibility, research reliability, social bonding
- MeSH terms
- Administration, Intranasal, Animals, Brain, Humans, Oxytocin, Research Design, Social Behavior, Statistics as Topic, Reproducibility of Results
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