Elsevier

Biological Psychiatry

Volume 79, Issue 3, 1 February 2016, Pages 251-257
Biological Psychiatry

Review
Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies

https://doi.org/10.1016/j.biopsych.2015.06.016Get rights and content

Abstract

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.

Section snippets

The Statistical Power Of Behavioral In-Ot Studies In Humans

Statistical power is the probability that a test will be able to reject the null hypothesis considering a true relation with a given effect size. True effect size values are, however, difficult, if not impossible, to acquire. This problem can to some extent be avoided by using effect size estimates from meta-analyses of relevant prior studies. 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

The Positive Predictive Value of Behavioral In-Ot Studies In Humans

The formula for calculating the PPV using information on power (1 − β), the prestudy odds (R; described below), and the alpha level (α) is PPV = [(1 − β) × R] / [(1 − β) × R + α].

Although rather exact values for both power (calculated above) and alpha level (most commonly set to 5%) can be put into this formula, picking a reasonable value for R is more problematic. Within any research field, both true and false hypotheses can be made. Thus, R represents the ratio of the number of true

Bias In Behavioral In-Ot Studies In Humans

When reading the literature on behavioral IN-OT studies in humans, it is obvious that most articles report positive findings, which is in line with a study by Fanelli (22) showing that more than 80% of scientific publications in various sciences report positive results. 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. But it seems very unlikely that all hypotheses about how IN-OT affects

Conclusions and Recommendations

Our analyses demonstrate that IN-OT studies are generally considerably underpowered. This leads to a high probability that the reported effects of IN-OT are overestimated. Also, underpowered studies are prone to other types of biases, such as the use of questionable research practices. The combination of low power and low prestudy odds results in low PPV estimates. Taken together, this suggests that most of the reported positive findings regarding how OT affects human behavior are likely to be

Acknowledgments and Disclosures

Preparation of this manuscript was supported by National Institutes of Health Grants R01MH096983 and 1P50MH100023. Additional funding was provided by National Institutes of Health Office of the Director Grant No.P51OD11132 to Yerkes National Primate Research Center.

HW thanks the Swedish Brain Foundation for financial support.

LJY has applied for a patent (US20120108510 – Methods of improving behavioral therapies) for combining melanocortin agonists with behavioral therapies to enhance social

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